1. 失眠的定义、流行病学与病理机制
1.1 失眠的核心定义与诊断标准
失眠是一种普遍存在的睡眠障碍，其核心特征表现为对睡眠数量或质量的不满意，并伴有入睡困难、维持睡眠困难或早醒等症状12。具体而言：
- 入睡困难 (Difficulty initiating sleep)：指躺下后30分钟内仍无法入睡。
- 维持睡眠困难 (Difficulty maintaining sleep)：指夜间醒来后难以再次入睡，或夜间觉醒次数过多、持续时间过长。
- 早醒 (Early morning awakening)：指比预期时间提早醒来，且无法再次入睡。
这些夜间症状通常会导致明显的日间功能损害，如疲劳、注意力不集中、情绪不稳、工作或学业表现下降等13。
在临床诊断中，主要依据《精神疾病诊断与统计手册第五版》（DSM-5）和《国际睡眠疾病分类第三版》（ICSD-3）的标准。DSM-5 将失眠定义为一种独立的疾病，不再将其视为其他精神或躯体疾病的次要症状，强调了失眠本身的临床关注优先级4。ICSD-3 则根据症状的持续时间将失眠分为慢性、短期和其他类型，使得全科医生能更便捷地进行诊断45。DSM-5和ICSD-3均将日间功能受损作为诊断失眠的重要标准，尽管不同诊断标准对日间症状的纳入程度存在差异，可能导致失眠患病率的报告存在较大范围的波动3。
急性失眠通常指失眠症状持续时间不足3个月。
慢性失眠则指失眠症状每周至少发生3次，并持续3个月以上46。与急性失眠不同，慢性失眠往往涉及更复杂的病理生理机制，如持续性过度觉醒，并且与多种躯体和精神疾病密切相关67。在DSM-5和ICSD-3中，失眠的诊断需要排除其他睡眠障碍或潜在的医学/精神疾病，尽管在实际操作中，失眠常常与其他疾病并存（共病）4。例如，对DSM-5诊断标准的印尼版睡眠状况指标（ISCI）进行研究发现，该工具能有效筛选中风后慢性期的失眠症，进一步验证了DSM-5诊断标准在特定人群中的适用性8。
1.2 流行病学特征与高危人群
失眠的流行病学特征复杂多样，不同人群的患病率差异显著，且受年龄、性别、生活方式等多种因素影响。全球范围内的研究表明，失眠是一种普遍存在的健康问题。
总体患病率
尽管诊断标准和评估方法有所不同，全球范围内失眠的总体患病率较高。在中国，一项荟萃分析显示，普通人群中失眠的汇总患病率为15.0%（95% CI: 12.1%-18.5%）9。这一数字虽然低于西方国家，但与亚洲其他国家相似9。
高危人群
失眠在高危人群中的患病率更高，这些群体通常面临特定的生理、心理和社会挑战：
- 老年人：老年人是失眠的高发群体。随着年龄增长，睡眠结构会发生显著变化，如深睡眠时间减少，入睡和维持睡眠的困难增加10。一项涵盖36个国家近百万老年参与者的系统评价和荟萃分析显示，老年人失眠的患病率高达29.0%11。老年人失眠的增加也与多种慢性疾病（如高血压、糖尿病、肾功能衰竭、呼吸系统疾病、疼痛、痴呆、抑郁和焦虑）的共病以及药物使用有关10。
- 更年期女性：更年期是女性失眠患病率显著增加的关键时期12。激素水平波动（特别是雌激素下降）与失眠密切相关13。一项针对更年期女性的荟萃分析显示，睡眠质量差的患病率高达50.8%（95% CI: 45.4-56.3%）14。潮热是导致更年期女性失眠的重要因素之一，失眠反过来也可能增加抑郁的风险12。此外，其他医学状况（如肥胖、胃食管反流、癌症、尿失禁、甲状腺功能障碍、慢性疼痛）以及行为和心理社会因素（如睡眠卫生差、饮酒、婚姻不满、育儿压力、经济担忧）也共同导致了更年期女性失眠的高发12。
- 退伍军人：现役军人及退伍军人是失眠的脆弱群体，这可能与创伤后应激障碍（PTSD）等精神健康问题的高度共病有关1516。
- 共病患者：失眠常与其他精神疾病和躯体疾病共存，形成恶性循环。
- 精神疾病：抑郁症、焦虑症、PTSD等精神障碍与失眠存在双向关联，即失眠既是这些疾病的症状，也可能加重其病程1317。
- 躯体疾病：慢性疼痛、癌症、心血管疾病、阻塞性睡眠呼吸暂停（OSA）等躯体疾病也显著增加了失眠的患病率101215。值得注意的是，共病性失眠和睡眠呼吸暂停（COMISA）是一种普遍存在的衰弱性疾病，约30%至50%的睡眠诊所OSA患者报告有失眠症状1819。COMISA患者的睡眠、日间功能、心理健康和身体健康状况均差于单纯失眠或单纯OSA患者19。一项研究发现，随着年龄的增长，COMISA的患病率显著增加，每增加一岁，COMISA的几率增加3%（95% CI: 1.02-1.04），这凸显了老年患者中COMISA的临床识别重要性20。
影响因素
- 年龄：如前所述，老年人失眠患病率更高，但一项针对中国人群的荟萃分析发现，在平均年龄小于43.7岁的人群中，失眠患病率（20.4%）显著高于平均年龄大于或等于43.7岁的人群（11.6%），这可能表明年轻人群面临不同的生活压力和睡眠习惯，导致失眠风险增加9。然而，这与普遍认为的“老年人失眠更多”的观点存在差异，可能反映了不同研究中失眠定义、评估工具以及研究人群特征的差异。
- 性别：女性在生命的不同阶段（如经期、孕期、更年期）由于激素波动，更容易出现失眠1213。例如，COMISA患者中女性比例更高（48% vs 24%）20。
- 生活方式和环境：不良的睡眠卫生习惯、过度摄入咖啡因或酒精、夜间工作、轮班工作、高压力生活以及不适宜的睡眠环境（如光线、噪音）均可诱发或加重失眠。此外，心理社会因素，如经济压力、家庭责任、人际关系问题等，也与失眠的发生发展密切相关12。
1.3 病理机制与神经生物学基础
失眠的病理机制复杂多样，涉及神经生物学、生理学和心理学多个层面，其中“过度觉醒理论”（Hyperarousal Theory）被广泛认为是理解慢性失眠核心机制的“最终共同通路”1212223。
1.3.1 过度觉醒理论
过度觉醒理论指出，失眠患者在生理、认知和情绪层面均表现出持续的过度觉醒状态，这种状态即使在白天和睡眠期间也依然存在122。
- 生理性过度觉醒：研究表明，失眠患者存在交感神经系统活动增强，表现为心率、体温、代谢率以及皮质醇水平的升高1。这些生理指标的异常升高，使得患者即使在夜间试图入睡时也难以进入深度放松状态，从而表现为入睡困难和睡眠维持障碍2122。神经影像学研究也观察到失眠患者大脑中与觉醒相关的区域（如脑干、丘脑、下丘脑和皮层）在睡眠期间的活动增强，而与睡眠启动和维持相关的区域（如前额叶皮层）活动相对减弱，这反映了觉醒系统与睡眠诱导系统之间的失衡12122。
- 认知性过度觉醒：失眠患者常表现出过度担忧睡眠、反复思考日间事件以及对睡眠相关刺激的高度警觉性。这种持续的思维活跃和焦虑情绪进一步阻碍了入睡和睡眠的连续性。
- 情绪性过度觉醒：失眠与情绪障碍（如焦虑和抑郁）紧密相关，负面情绪本身就是一种觉醒状态，会通过影响神经内分泌系统，如下丘脑-垂体-肾上腺（HPA）轴的过度活跃，进一步加剧生理性觉醒，形成恶性循环12425。
综合来看，过度觉醒可以被概念化为一种由遗传易感性、心理社会应激源和不良睡眠行为及认知因素相互作用导致的最终共同通路，其核心在于觉醒与睡眠诱导的脑活动之间的不平衡22。
1.3.2 睡眠-觉醒调节系统的异常
睡眠-觉醒周期是一个由多种神经递质和神经调质精确调控的复杂过程。失眠的发生与这些关键调节分子的功能异常密切相关262728。
- 食欲素（Orexin/Hypocretin）：食欲素是下丘脑分泌的一种神经肽，在维持觉醒状态和调节食欲方面发挥关键作用2729。食欲素神经元投射到大脑的多个区域，包括那些参与觉醒和情绪调节的区域。失眠患者可能存在食欲素系统过度活跃，导致觉醒信号增强，抑制睡眠。针对食欲素受体的拮抗剂（如DORAs）被开发用于治疗失眠，通过阻断食欲素的觉醒作用来促进睡眠。
- 腺苷（Adenosine）：腺苷是一种重要的睡眠诱导物质，在长时间觉醒后会在大脑中积累，产生睡眠压力，促进睡眠的发生2729。咖啡因等物质通过阻断腺苷受体来发挥其促觉醒作用。在失眠患者中，腺苷的生成、代谢或受体功能可能存在异常，导致睡眠压力不足以克服过度觉醒。
- GABA（γ-氨基丁酸）：GABA是中枢神经系统中主要的抑制性神经递质，通过抑制神经元活动来促进睡眠2627。许多安眠药（如苯二氮卓类和Z-药物）通过增强GABA能系统的功能来发挥镇静催眠作用。失眠患者可能存在GABA能系统活性不足或受体敏感性下降。
- 褪黑素（Melatonin）：褪黑素由松果体分泌，参与调节昼夜节律和睡眠-觉醒周期。它主要通过调节生物钟来促进睡眠。失眠患者可能存在褪黑素分泌节律紊乱或水平不足。
- 其他神经递质：多巴胺、去甲肾上腺素、组胺、乙酰胆碱和5-羟色胺等神经递质也都在睡眠-觉醒调节中扮演重要角色262728。这些神经递质系统的失衡，无论是觉醒促进性递质的过度活跃还是睡眠促进性递质的不足，都可能导致失眠。
1.3.3 共病精神/躯体疾病的协同作用
失眠很少单独存在，常常与多种精神和躯体疾病相互影响，形成复杂的共病关系21。这种共病性不仅增加了失眠的复杂性，也加重了原发疾病的负担。
- 抑郁和焦虑：失眠与抑郁症和焦虑症之间存在显著的双向关系30313233。失眠是抑郁症最常见的症状之一，也是其发展和复发的独立危险因素32。反之，抑郁和焦虑会通过持续的负面情绪、认知过度活跃以及HPA轴的过度激活，加剧失眠的生理和认知觉醒24253133。神经生物学研究表明，失眠和抑郁可能共享重叠的分子通路，例如脑源性神经营养因子（BDNF）水平的降低与应激相关的失眠和抑郁均有关242531。
- 心血管疾病（CVD）：慢性失眠与心血管疾病（如高血压、冠心病和心力衰竭）的发病率和死亡率增加相关34。其机制可能与下丘脑-垂体轴功能紊乱、交感神经系统活动增强以及炎症反应增加有关34。肠道菌群-胆汁酸轴也可能连接慢性失眠与心血管代谢疾病之间的正相关关系35。长期失眠导致的睡眠剥夺和应激反应会增加心血管负荷，从而提升CVD风险。
- 代谢性疾病：失眠，尤其是伴有短睡眠时间的失眠，与代谢综合征（如胰岛素抵抗、血脂异常）和肥胖的风险增加有关36。睡眠不足会影响食欲调节激素（如瘦素和生长素）的平衡，导致食欲增加和能量摄入过多，进而促进体重增加36。
- 神经退行性疾病：失眠已被确定为中风和痴呆的风险因素37。尽管有观察性研究表明失眠与卒中和痴呆风险增加相关，但孟德尔随机化研究仅支持遗传预测的失眠与卒中风险的因果关系，而与痴呆或小血管疾病标志物无关，这提示需要谨慎对待失眠干预对痴呆的预防作用37。
- 慢性疼痛和炎症：慢性疼痛是导致失眠的常见原因，而失眠反过来会降低疼痛阈值，加剧疼痛感，形成恶性循环。失眠引起的持续应激反应和睡眠碎片化还可能导致慢性炎症状态，进一步影响多个器官系统。
总而言之，失眠的病理机制是多因素的，过度觉醒是其核心特征，而睡眠-觉醒调节系统的异常以及与共病疾病的复杂相互作用，共同构成了失眠的复杂图景。深入理解这些机制对于开发更精准、更有效的治疗策略至关重要2138。
2. 失眠的系统评估与鉴别诊断
对失眠进行全面、系统的评估是制定有效干预策略的基础。这不仅包括对失眠症状本身的评估，还涉及鉴别诊断其他睡眠障碍以及筛查共病的精神或躯体疾病。
2.1 临床评估工具与方法
失眠的临床评估通常结合主观报告和客观测量工具，以全面了解患者的睡眠模式、失眠严重程度及其对日间功能的影响。
2.1.1 主观评估工具
主观评估工具主要通过问卷和日记形式收集患者自我报告的睡眠信息，具有操作简便、成本效益高、能反映患者主观感受等优点。
- 睡眠日记 (Sleep Diary)：睡眠日记是失眠评估中最为基础且重要的工具之一 39。患者通常需要连续填写1-2周，记录每日的就寝时间、入睡潜伏期（从上床到入睡所需时间）、夜间觉醒次数和时长、最终起床时间、总睡眠时间、睡眠质量评分以及日间小睡情况等。睡眠日记能够提供详细、连续的睡眠模式信息，帮助临床医生识别不健康的睡眠习惯，如不规律的作息、过长的卧床时间等，并为后续的治疗（特别是认知行为疗法，CBT-I）提供基线数据和疗效监测依据。
- 失眠严重程度指数 (Insomnia Severity Index, ISI)：ISI是一个广泛应用的自评问卷，用于评估失眠的严重程度。它包含7个条目，涵盖了入睡和维持睡眠的困难、对睡眠问题的担忧程度、对日间功能的影响以及对生活质量的满意度等 40。ISI的总分范围为0-28分，得分越高表示失眠越严重。研究表明，ISI具有良好的信效度，对于识别失眠病例（临界值通常设为10分，敏感性86.1%，特异性87.7%）和评估治疗反应（分数变化大于或等于8.4分通常被认为是中等程度的改善）均有效 40。
- 匹兹堡睡眠质量指数 (Pittsburgh Sleep Quality Index, PSQI)：PSQI是另一个常用的自评问卷，用于评估过去一个月的睡眠质量。它包含19个自评条目和5个他评条目（他评条目不计分），最终生成7个成分得分（主观睡眠质量、入睡时间、睡眠时间、睡眠效率、睡眠障碍、催眠药物使用和日间功能障碍），这些成分得分累加形成一个总分，范围为0-21分。总分大于5分通常提示存在睡眠障碍 41。PSQI对原发性失眠患者具有较高的重测信度和良好效度 41，广泛用于临床筛查和研究。
- 爱丁堡产后抑郁量表 (Edinburgh Postnatal Depression Scale, EPDS)：虽然主要用于筛查产后抑郁，但其在特定人群中也可作为评估情绪障碍与失眠共病的辅助工具，尤其在妊娠和产后女性中，失眠常与情绪问题并存。
2.1.2 客观评估工具
客观评估工具通过生理测量提供不依赖患者主观报告的睡眠数据，对于鉴别诊断、评估治疗效果和研究睡眠生理学机制具有重要价值。
- 多导睡眠监测 (Polysomnography, PSG)：PSG被认为是睡眠障碍诊断的“金标准” 39。它通过同时记录脑电图（EEG）、眼电图（EOG）、肌电图（EMG）、心电图（ECG）、呼吸气流、呼吸运动、血氧饱和度、腿动等多个生理信号，提供全面的睡眠结构（如睡眠分期、睡眠效率、觉醒次数）和睡眠相关呼吸事件、肢体运动等信息。尽管PSG在失眠诊断中并非常规必要，但当怀疑存在其他睡眠障碍（如睡眠呼吸暂停、周期性肢体运动障碍）、治疗无效的顽固性失眠、高风险职业人群或怀疑存在显著睡眠状态误判时，PSG是强烈推荐的鉴别诊断工具 39 42。
- 体动记录仪 (Actigraphy)：体动记录仪是一种佩戴在手腕上类似手表的设备，通过记录肢体活动来间接评估睡眠-觉醒模式 39。它能连续监测数天甚至数周的睡眠数据，如总睡眠时间（TST）、入睡潜伏期（SOL）、夜间觉醒时间（WASO）、睡眠效率（SE）以及昼夜节律模式。体动记录仪的优势在于其便携性和长期监测能力，能够在患者自然睡眠环境中收集数据，提供比单次PSG更能反映日常睡眠状况的信息。与睡眠日记相比，体动记录仪提供了客观的睡眠数据，减少了主观报告偏差。有研究表明，体动记录仪能有效评估太极拳或常规运动对老年失眠患者睡眠效率和觉醒次数的改善 43。此外，体动记录仪在评估抑郁和焦虑障碍患者的睡眠、昼夜节律和体力活动模式方面也显示出良好的生态学效度 44。然而，体动记录仪无法进行睡眠分期，也无法直接诊断睡眠呼吸暂停等疾病，其准确性可能受限于算法和个体差异。
- 智能穿戴设备 (Smart Wearable Devices)：近年来，智能手环、智能手表等穿戴设备也开始被用于睡眠监测。这些设备通常集成光电容积描记（PPG）传感器、加速度计等，可以估计心率、血氧、活动量等数据，进而推断睡眠时长和分期。虽然其准确性通常低于医用级体动记录仪和PSG，但由于其高度可及性和用户友好性，在日常健康监测和初步筛查中发挥着越来越重要的作用。例如，有研究利用智能手环监测数字CBT-I干预后的总睡眠时间（TST）和睡眠效率（SE）的改善 45。
综合运用这些主客观评估工具，可以为失眠患者提供一个全面的诊断和治疗基线，从而制定个性化的干预方案。
2.2 与其他睡眠障碍的鉴别
失眠症状往往与其他睡眠障碍的临床表现有所重叠，因此，在评估过程中进行细致的鉴别诊断至关重要。这有助于避免误诊和延误针对性治疗，尤其是在失眠与其他睡眠障碍共存的情况下。
2.2.1 阻塞性睡眠呼吸暂停 (Obstructive Sleep Apnea, OSA)
阻塞性睡眠呼吸暂停（OSA）是一种以睡眠期间反复发作性上气道塌陷导致呼吸暂停或低通气为特征的睡眠障碍。尽管OSA以白天嗜睡或疲劳为典型症状，但许多OSA患者（约30%至50%）也报告存在失眠症状，这种共病情况被称为共病性失眠和睡眠呼吸暂停（COMISA） 1846。COMISA患者的睡眠障碍症状比单独患有失眠或OSA的患者更为严重，治疗也更具挑战性 1846。
鉴别要点：
- 症状表现：单纯失眠患者主要抱怨入睡困难、睡眠维持困难或早醒，通常没有夜间打鼾、憋气、呼吸中断等症状。而OSA患者，即使合并失眠，也常伴有响亮的不规律打鼾、目击者报告的呼吸暂停、夜间频繁觉醒伴憋气感、白天过度嗜睡、晨起头痛、口干等 47。女性OSA患者可能更常以失眠而非典型的嗜睡来表现 48。
- 诊断工具：多导睡眠监测（PSG）是鉴别失眠与OSA的金标准。PSG可以客观记录呼吸事件（如呼吸暂停、低通气）的频率和严重程度（通过呼吸暂停-低通气指数，AHI），以及睡眠结构和血氧饱和度的变化。在怀疑COMISA时，PSG是必不可少的。对于单纯失眠，PSG可能显示睡眠效率低下、入睡潜伏期延长等，但无显著呼吸事件。
- 共病影响：COMISA患者不仅睡眠质量更差，还可能面临更高的心血管疾病（如高血压、心血管疾病）风险和全因死亡风险 49，并且可能影响阳痿的发生 50。COMISA中的自主神经系统功能障碍表现为清醒时副交感神经活动减少和睡眠时交感神经活动增强 51。
2.2.2 昼夜节律睡眠-觉醒障碍 (Circadian Rhythm Sleep-Wake Disorders, CRSWD)
昼夜节律睡眠-觉醒障碍是由于人体生物钟与外部24小时环境周期不同步，或生物钟本身功能障碍导致的睡眠问题。
鉴别要点：
- 症状表现：CRSWD患者的核心问题是睡眠时间不匹配社会常规时间，但一旦在符合其内在生物钟的时间入睡，睡眠质量通常是正常的。例如，延迟睡眠时相障碍（DSWPD）患者表现为入睡和醒来时间比社会常规时间晚，导致夜间入睡困难和早晨醒来困难。提前睡眠时相障碍（ASWPD）则相反，表现为过早入睡和过早醒来。而不规则睡眠-觉醒节律障碍则表现为全天睡眠和觉醒时间分布不规律。单纯失眠则是在任何试图入睡的时间都可能面临困难，且睡眠质量不佳。
- 睡眠日记：详细的睡眠日记记录可以帮助识别CRSWD患者特有的睡眠-觉醒时间模式，例如持续晚睡晚起，或多片段睡眠等。
- 体动记录仪：长期（数周）的体动记录仪监测能更客观地呈现患者的昼夜节律周期和睡眠-觉醒分布。
2.2.3 不宁腿综合征 (Restless Legs Syndrome, RLS)
不宁腿综合征（RLS）是一种神经感觉运动障碍，主要表现为夜间或休息时出现腿部不适感，通常伴有难以抑制的移动双腿的冲动。RLS是导致失眠的常见原因之一 5253，多达25%的睡眠障碍患者可能患有RLS或周期性肢体运动障碍（PLMS） 52。
鉴别要点：
- 症状表现：RLS的典型症状包括：腿部不适感（如蚁走感、瘙痒、疼痛、电击感等）通常在休息或不活动时出现或加重；通过移动腿部可以暂时缓解不适感；症状在傍晚或夜间加重。这些不适感导致患者难以入睡或频繁觉醒，从而表现出失眠。单纯失眠患者通常没有腿部不适感及移动双腿的冲动。
- 诊断标准：RLS的诊断主要依赖于患者的主观症状描述，依据国际不宁腿综合征研究组（IRLSSG）的诊断标准。
- 周期性肢体运动障碍 (PLMS)：PLMS常与RLS共存，指睡眠期间肢体（通常是腿部）周期性、刻板性地屈曲运动。PLMS可以通过PSG客观记录，表现为肌电图上的周期性活动。PSG也可以帮助鉴别RLS，尤其是在症状描述不典型时。
2.2.4 发作性睡病 (Narcolepsy)
发作性睡病是一种慢性神经系统疾病，其特征是白天过度嗜睡，即使在充分睡眠后仍无法缓解 54。虽然核心症状是嗜睡，但发作性睡病患者的夜间睡眠也常受扰，表现为失眠症状。
鉴别要点：
- 核心症状：发作性睡病的核心是无法抗拒的白天嗜睡发作，常伴有猝倒（情绪激动时突然肌肉张力丧失）、入睡前幻觉和睡眠瘫痪（俗称“鬼压床”）等伴随症状 54。单纯失眠患者通常不会出现白天无法控制的嗜睡发作。
- 诊断测试：诊断发作性睡病需要进行多导睡眠监测（PSG）和多次小睡潜伏期测试（MSLT）。MSLT会显示极短的平均入睡潜伏期（通常小于8分钟）以及睡眠起始的快速眼动期（SOREM）的出现。
- 夜间睡眠：虽然白天嗜睡是发作性睡病的主要特征，但夜间睡眠的碎片化和失眠症状也常见，这可能导致其与单纯失眠混淆。然而，发作性睡病的失眠往往是其整体睡眠-觉醒障碍的一部分，而非孤立的入睡或维持睡眠困难。
2.2.5 共病失眠的识别难点
失眠常常作为其他睡眠障碍或疾病的伴随症状出现，这使得共病失眠（例如COMISA）的识别变得复杂。
- 症状掩盖：其他睡眠障碍（如OSA、RLS）的典型症状可能掩盖了失眠的存在，或者失眠症状被错误地归因于其他原发疾病。例如，OSA患者的夜间觉醒可能是由于呼吸暂停事件引起的，而不是单纯的失眠。
- 诊断挑战：单一症状的诊断可能不足以反映患者的全貌。对于报告失眠症状的患者，临床医生需要保持警惕，筛查其他潜在的睡眠障碍，并进行全面的评估。例如，对于OSA患者，常规的问卷筛查或睡眠日记应包括对失眠症状的评估。
- 治疗复杂性：共病失眠的治疗需要同时针对两种或多种疾病，如果只治疗其中一种，可能无法有效缓解患者的整体症状。例如，对于COMISA，单纯治疗OSA（如佩戴CPAP）可能无法完全解决失眠问题，需要结合CBT-I等针对失眠的干预措施 18。
鉴别诊断的关键在于全面评估患者的睡眠史、日间功能、进行必要的客观睡眠检测，并结合患者的具体症状特点，从而明确诊断并制定个性化的治疗方案。
2.3 共病情况的筛查与评估
失眠往往不是一个孤立的问题，而是多种精神和躯体疾病的常见共病，且二者之间存在复杂的双向关联。因此，对失眠患者进行全面的共病筛查与评估至关重要，以确保采取综合性的干预策略。忽视共病不仅可能导致失眠治疗效果不佳，还可能加重原发疾病的进展和预后 55。
2.3.1 精神疾病共病
失眠与精神疾病，特别是情绪障碍和焦虑障碍，具有极高的共病率，并且这种关系是双向的：失眠既是许多精神疾病的症状，也可能是其发生、发展和复发的风险因素 30。
- 抑郁症与焦虑症：
失眠是抑郁症和焦虑症最常见的症状之一。大约70%的精神疾病患者报告有睡眠困难，其中30%符合失眠症的诊断标准 56。反过来，长期失眠会显著增加抑郁症和焦虑症的风险。研究表明，治疗失眠可以改善其他精神健康问题 55。因此，在评估失眠患者时，应常规筛查抑郁症状（如使用PHQ-9量表）和焦虑症状（如使用GAD-7量表）。对于已诊断为抑郁症或焦虑症的患者，其失眠问题也应被视为一个独立的治疗目标，而不仅仅是原发疾病的次要症状。 - 创伤后应激障碍（PTSD）：
睡眠障碍和噩梦是PTSD的核心症状 57。PTSD患者普遍存在睡眠质量差、失眠和夜间焦虑症状，以及噩梦和应激性梦境。这种关系也是双向的，持续的睡眠障碍可能影响PTSD的病程 57。针对PTSD患者的失眠评估应包括详细的睡眠史，关注噩梦的频率和内容，并可使用失眠严重程度指数（ISI）等工具。对于退伍军人等高风险人群，尤其应警惕PTSD与失眠的共病 58。针对癌症患者的COVID-19大流行期间的研究也显示，大约五分之一的老年癌症患者报告有PTSD症状，且其失眠症状较为普遍 5960。 - 其他精神障碍：
失眠也常见于双相情感障碍、精神病性障碍和物质使用障碍（如酒精依赖）等。酒精依赖患者的失眠通过认知行为疗法（CBT-I）治疗可以有效改善失眠严重程度和酒精依赖症状 56。对这些患者的评估需要更细致的病史询问，以及针对性地使用精神科评估工具。
2.3.2 躯体疾病共病
失眠也与多种躯体疾病密切相关，这些疾病可能直接导致失眠，或因其治疗方案而加重失眠。
- 慢性疼痛：
慢性疼痛患者中失眠的患病率很高 6162。疼痛本身会干扰睡眠，导致入睡困难和夜间觉醒。反之，失眠又会降低疼痛阈值，使疼痛感知更为强烈，形成恶性循环 61。神经炎症和中枢敏化机制被认为是连接慢性疼痛和失眠的关键通路 61。例如，前扣带皮层（ACC）锥体神经元的过度活跃被发现是慢性疼痛相关失眠的神经环路机制 63。在评估慢性疼痛患者的失眠时，应详细询问疼痛部位、性质、程度及其对睡眠的影响。同时，止痛药物也可能影响睡眠质量，特别是阿片类药物已被证实会对睡眠产生负面影响 64。 - 癌症：
癌症患者的失眠问题非常普遍，患病率高于普通人群 6566。失眠不仅增加了癌症患者的症状负担，还严重影响其生活质量 65。癌症相关的失眠可能由多种因素引起，包括癌症本身（如疼痛、恶心、呼吸困难）、治疗副作用（如化疗、放疗引起的疲劳、恶心、疼痛）、心理压力（如对疾病的担忧、焦虑、抑郁）以及激素变化等 65。某些特定癌症（如肺癌、乳腺癌、头颈部肿瘤）的患者失眠尤为突出，老年女性癌症患者似乎更易感 65。研究也提示失眠可能影响卵巢癌的风险和生存率 67。对癌症患者的失眠筛查应常规进行，并注意评估疼痛、疲劳、潮热等共存症状，因为这些症状的管理有助于改善失眠 65。 - 心血管疾病：
高血压、冠心病和心力衰竭等心血管疾病患者常伴有失眠。失眠可能通过激活交感神经系统、炎症反应以及影响血压调节等机制，增加心血管事件的风险。评估时需关注患者的心血管病史、用药情况及相关症状。 - 其他躯体疾病：
慢性阻塞性肺疾病（COPD）、哮喘、胃食管反流病、甲状腺功能亢进、帕金森病等多种躯体疾病，都可能通过不同的机制导致失眠。例如，呼吸困难、夜间咳嗽、胃灼热等症状都会直接干扰睡眠。
2.3.3 跨学科评估框架
鉴于失眠共病的复杂性，建议采用跨学科评估框架，以确保全面识别和管理患者的多种问题：
初步筛查：
- 睡眠问卷：所有失眠患者应常规填写如ISI、PSQI等睡眠问卷，以量化失眠严重程度和睡眠质量。
- 精神健康筛查：使用如PHQ-9（抑郁）、GAD-7（焦虑）等简单有效的筛查工具，快速识别精神疾病共病。对于有创伤史的患者，考虑PTSD筛查。
- 疼痛筛查：评估疼痛部位、强度（使用视觉模拟评分VAS或数字评定量表NRS）及其对睡眠的影响。
- 其他躯体症状：询问是否存在呼吸困难、胃肠不适、潮热、不宁腿等症状。
详细病史询问：
- 睡眠史：详细了解失眠的起始时间、持续时间、症状特点（入睡困难、维持困难、早醒）、频率、严重程度，以及既往尝试的治疗方法和效果。
- 用药史：仔细审查患者目前正在使用的所有药物，包括处方药、非处方药和补充剂，以识别可能影响睡眠的药物。
- 生活方式：评估咖啡因、酒精、尼古丁使用情况，以及日常作息、饮食习惯和运动量。
- 社会心理因素：了解患者的职业、家庭环境、压力水平和应对机制。
客观评估：
- 睡眠日记：要求患者填写1-2周的睡眠日记，以获得详细、连续的睡眠行为数据。
- 多导睡眠监测（PSG）：对于怀疑存在睡眠呼吸暂停、周期性肢体运动障碍、发作性睡病或其他复杂睡眠障碍的患者，或对一线治疗无效的顽固性失眠，PSG是鉴别诊断的必要手段。
- 体动记录仪：在无法进行PSG或需要长期监测睡眠-觉醒节律时，体动记录仪可作为辅助工具。
多学科会诊：
当评估提示存在复杂共病情况时，应考虑进行多学科会诊，如转诊至精神科医生、疼痛专家、呼吸科医生或肿瘤科医生，共同制定综合性的治疗方案。例如，对于慢性疲劳综合征（CFS）的患者，多学科方法评估显示，只有少数患者符合纯粹的CFS诊断，多数存在睡眠障碍和精神障碍的共病，突显了多学科评估的重要性 68。
通过这种系统化的评估方法，可以确保对失眠患者的全面理解，从而提供更精准、更有效的个体化治疗。
3. 非药物干预的核心方法与实践
非药物干预被认为是失眠症，尤其是慢性失眠症的一线治疗方法，其优势在于无药物副作用、长期疗效显著且能有效改善日间症状 6970。在所有非药物干预中，认知行为疗法（CBT-I）因其坚实的证据基础和全面性而备受推荐。
3.1 认知行为疗法（CBT-I）的实施与证据
认知行为疗法（CBT-I）被广泛认为是慢性失眠症的一线治疗方案，其疗效优于药物，并能提供长期管理 697071。CBT-I是一种多组分干预措施，旨在纠正导致和维持失眠的错误信念、不健康的行为和生理过度觉醒。它的核心技术包括刺激控制、睡眠限制、认知重构以及放松训练和睡眠卫生教育等 697273。研究表明，CBT-I不仅能显著改善夜间睡眠症状，还能有效缓解日间疲劳、抑郁和焦虑等共病症状 7475。
3.1.1 CBT-I的核心技术
刺激控制 (Stimulus Control Therapy, SCT)
刺激控制旨在打破床铺和卧室内导致失眠的条件反射。其核心原则是将床和卧室与睡眠重建积极联系，而非与觉醒和挫败感联系。具体措施包括：- 只在感到困倦时才上床睡觉。
- 床只用于睡眠和性活动，避免在床上阅读、看电视、使用电子设备或进食。
- 如果在上床后20分钟内无法入睡，或者夜间醒来后无法再次入睡，应离开卧室到其他房间进行放松活动，待重新感到困倦后再回床上睡觉。
- 每天无论前一晚睡得如何，都要在固定时间起床，以帮助稳定昼夜节律。
睡眠限制 (Sleep Restriction Therapy, SRT)
睡眠限制疗法旨在通过适度剥夺睡眠来增强睡眠驱动力（homeostatic sleep drive），提高睡眠效率。这是一种反直觉但非常有效的技术 76777879。- 初始阶段：根据患者的睡眠日记，计算其平均总睡眠时间（通常是自我报告的），并以此作为最初的“卧床时间”。例如，如果患者每天平均只睡5小时，那么最初的卧床时间就被限制在5小时内（如凌晨1点到早上6点）。
- 逐步调整：一旦患者的睡眠效率（睡眠时间/卧床时间）达到某个预设阈值（通常是85%或更高），就可以逐步增加卧床时间（如每周增加15-30分钟）。
- 目标：最终目标是找到一个既能保证足够睡眠量又能维持高睡眠效率的卧床时间。
睡眠限制疗法的证据强大。一项针对护士提供睡眠限制疗法的研究（HABIT试验）显示，与睡眠卫生组相比，睡眠限制疗法能显著降低失眠严重程度指数（ISI），且在3、6和12个月时效果持续，并具有成本效益 7678。一项成分网络元分析发现，睡眠限制疗法是CBT-I中最有效的组分，能显著改善自我报告的睡眠连续性和睡眠质量 79。
认知重构 (Cognitive Restructuring)
认知重构针对的是与失眠相关的负面思维模式和不切实际的期望。失眠患者常存在对睡眠的灾难化思维（如“我如果今晚睡不好，明天就会一团糟”）、对睡眠时间的需求存在误解（如认为必须睡够8小时才健康）以及对睡眠过度关注等。- 识别和挑战：治疗师会帮助患者识别这些自动化、扭曲的思维，并挑战其合理性。
- 替换：引导患者用更现实、更积极的信念来替换负面思维，例如“即使今晚睡得不好，我也能应对明天的挑战”。
- 减少担忧：通过认知重构，减少患者对睡眠的担忧和过度关注，从而降低认知性过度觉醒。
研究表明，认知重构是CBT-I的关键组分，与失眠缓解的增量比值比（iOR）为1.68（95% CI, 1.28-2.20），对改善主观睡眠质量特别有效 77。
放松训练 (Relaxation Training)
放松训练旨在降低生理性过度觉醒，包括渐进性肌肉放松、腹式呼吸、引导式想象等技术。这些技术通过主动放松身体，减少焦虑和紧张感，从而促进睡眠。睡眠卫生教育 (Sleep Hygiene Education)
睡眠卫生教育提供关于健康睡眠习惯的指导，尽管其单独作为失眠治疗的证据强度有限，但作为CBT-I的辅助组分非常重要。内容包括：
3.1.2 CBT-I的长期疗效
多项研究和荟萃分析证实，CBT-I对慢性失眠具有显著且持久的疗效 697071。与药物治疗相比，CBT-I的疗效在停药后仍能维持，且复发率较低。在一项评估CBT-I有效性的系统回顾和荟萃分析中，结果显示CBT-I能显著改善入睡潜伏期（SOL）、夜间觉醒时间（WASO）、总睡眠时间（TST）和睡眠效率（SE%），并且这些改善在治疗后仍然持续 71。对于老年人而言，CBT-I被推荐作为失眠的一线治疗，且其长期管理效果优于药物 69。
CBT-I对共病症状的改善也得到了证实。它不仅能改善失眠本身，还能有效减轻抑郁症状、焦虑症状、日间疲劳和提高生活质量 7475。例如，在患有骨关节炎疼痛的老年人中，电话CBT-I不仅显著改善了失眠，还减轻了疲劳 80。
3.1.3 数字CBT-I（dCBT-I）的可及性优势
尽管CBT-I是首选的一线治疗，但其普及性受到治疗师短缺、地域限制和费用等因素的制约。数字认知行为疗法（dCBT-I）应运而生，通过互联网、移动应用程序或电话平台提供CBT-I干预，极大地提高了治疗的可及性、便利性和可扩展性 818283。
- 广泛可及性：dCBT-I克服了传统CBT-I对受过培训治疗师的需求和地域限制，使得更多患者能够获得循证治疗。例如，在法国，dCBT-I已被开发为第一个可开处方的数字疗法，旨在解决传统CBT-I可及性不足的问题 82。
- 疗效证据：大量研究表明，dCBT-I与面对面CBT-I同样有效，甚至在某些方面表现出非劣效性 8283。一项包含33项研究的荟萃分析发现，dCBT-I能显著降低失眠严重程度指数（ISI），并且这种改善在短期和长期随访中均能持续 83。
- 特殊人群应用：dCBT-I在特殊人群中也显示出潜力。对于青少年和年轻人，dCBT-I被证明是治疗失眠的有效方法，尤其是在改善自我报告的睡眠质量方面 84。针对抑郁症青少年和年轻人的护士主导dCBT-I已被证明能有效降低失眠和抑郁症状 85。此外，dCBT-I作为常规护理的辅助手段，还能显著改善伴有共病抑郁症患者的抑郁症状和失眠严重程度 86。
- 灵活性和依从性：dCBT-I允许患者在自己的时间和地点进行治疗，增加了治疗的灵活性和私密性，有助于提高患者的依从性。一些dCBT-I项目还整合了智能评估和日常智能调整功能，以实现数字化表型分析和提供个性化治疗 82。
- 潜在局限性：尽管dCBT-I有诸多优势，但也存在一些潜在的局限性，例如可能需要一定的技术素养，并且在缺乏教练支持的情况下，其效果可能略逊于面对面CBT-I 81。然而，研究发现，dCBT-I的核心组件（如时间限制、刺激控制、放松技术、认知疗法和睡眠卫生/教育）和结构与传统CBT-I保持一致，并且许多项目都包含不同类型和形式的教练支持 81。
综上所述，CBT-I作为慢性失眠的一线非药物治疗，通过其多组分技术（刺激控制、睡眠限制、认知重构等）有效改善睡眠和日间功能，并具有长期疗效。数字CBT-I的兴起则极大地拓展了这一有效疗法的可及性，使其成为解决全球失眠问题的重要策略。
3.2 睡眠卫生与生活方式调整
睡眠卫生（Sleep Hygiene）是指一系列有助于促进良好睡眠习惯和环境的实践和行为，是失眠管理的重要组成部分，常作为认知行为疗法（CBT-I）的辅助部分，或在轻度失眠中作为独立干预措施 87。尽管有研究指出，睡眠卫生单独对失眠的改善效果有限 7088，但它在维持健康睡眠模式、预防失眠复发以及作为综合干预的一部分时，仍具有不可忽视的价值 87。
睡眠质量定义为个体对睡眠体验所有方面的自我满意度，其关键属性包括睡眠效率、入睡潜伏期、睡眠持续时间以及入睡后觉醒时间 89。良好的睡眠卫生实践正是围绕这些属性展开。
3.2.1 作息规律与睡眠环境优化
- 保持规律的作息时间：
维持一个固定的睡觉和起床时间至关重要，即使在周末也应尽量保持一致 87。规律的作息有助于稳定人体的昼夜节律，使其与外部环境同步，从而促进睡眠-觉醒周期的正常运作。即使前一晚睡得不好，也要坚持在固定时间起床，这有助于增强第二天的睡眠驱动力，并调整生物钟。 - 优化睡眠环境：
理想的睡眠环境应是黑暗、安静、凉爽且舒适的 87。- 光线：睡前应避免强光暴露，尤其是来自电子设备的蓝光，因为光线会抑制褪黑素的分泌，影响入睡 90。卧室应尽量保持黑暗，可使用遮光窗帘或眼罩。
- 噪音：噪音是睡眠的主要干扰因素之一。保持卧室安静，必要时可使用耳塞或白噪音机来屏蔽外部噪音。
- 温度：卧室温度应适中偏凉爽，通常建议在18-22摄氏度之间，过热或过冷都会影响睡眠质量。
- 床垫和枕头：选择舒适的床垫和枕头，确保身体得到良好支撑，有助于减少夜间不适。
3.2.2 避免刺激物与不良习惯
- 限制咖啡因摄入：
咖啡因是一种中枢神经系统兴奋剂，能够延长入睡潜伏期、减少总睡眠时间、降低睡眠效率，并减少慢波睡眠 9192。一项系统回顾和荟萃分析显示，咖啡因摄入会使总睡眠时间减少45分钟，睡眠效率降低7% 91。为了避免咖啡因对睡眠的负面影响，建议在睡前至少8.8小时避免饮用咖啡（每250毫升含107毫克咖啡因），对于含有更高咖啡因的预锻炼补充剂（217.5毫克），应在睡前至少13.2小时避免摄入 91。 - 避免酒精：
酒精虽然初期可能导致困倦，但其对睡眠结构有显著负面影响。酒精会碎片化睡眠，减少深度睡眠（慢波睡眠）和快速眼动（REM）睡眠，并增加夜间觉醒次数，从而导致睡眠质量下降 87。因此，睡前应避免饮酒。 - 戒烟或避免睡前吸烟：
尼古丁同样是一种兴奋剂，会干扰睡眠。吸烟者通常有更高的失眠患病率和更差的睡眠质量。 - 避免睡前进食过饱或辛辣食物：
睡前进食过饱或摄入辛辣食物可能导致消化不良和胃肠不适，从而影响睡眠。 - 避免白天过度小睡：
长时间或过晚的小睡会减少夜间的睡眠驱动力，使夜间入睡更加困难。如果需要小睡，建议将其控制在20-30分钟以内，并尽量在下午早些时候进行。 - 睡前放松活动：
睡前一小时避免剧烈运动和刺激性活动，如看电视、玩电子游戏、处理工作事务等。可以进行一些放松活动，如阅读纸质书、听轻音乐、温水泡澡或进行冥想。
3.2.3 运动与正念冥想等辅助方法
- 规律运动：
规律的体育锻炼对改善睡眠质量具有显著益处 8790。运动可以帮助减轻压力和焦虑，促进身体疲劳，从而更容易入睡。 - 正念冥想 (Mindfulness Meditation)：
正念冥想是一种通过有意识地关注当下，不加评判地观察自己的思想、情感和身体感觉的练习。它已被证明对改善睡眠质量有效 9899。 - 其他互补疗法：
除了上述方法，音乐疗法、针灸等互补疗法也被探索用于改善失眠。例如，音乐疗法被认为可以通过放松身心来促进睡眠。针灸则可能通过调节神经内分泌系统来改善睡眠。然而，这些辅助疗法的证据强度通常低于CBT-I和规律运动，通常建议作为CBT-I的补充，而非替代。
综上所述，睡眠卫生和健康的生活方式调整是失眠管理的基础。通过采纳规律作息、优化睡眠环境、避免刺激物以及进行适度运动和正念冥想，患者可以显著改善睡眠质量，提升整体健康水平。
3.3 辅助疗法的应用与局限
除了认知行为疗法（CBT-I）和基础睡眠卫生外，多种辅助疗法也被探索用于改善失眠。这些方法通常被视为互补性干预，旨在通过不同的机制支持睡眠，但其证据强度和适用范围各不相同，通常建议作为CBT-I的补充而非替代。
3.3.1 音乐疗法
音乐疗法是一种非药物干预手段，通过听音乐来促进放松、减轻焦虑和改善睡眠质量。
- 改善机制：音乐被认为可以通过影响自主神经系统，降低心率、呼吸频率和血压，从而诱导放松状态。此外，特定的音乐节奏和旋律可能有助于分散对睡眠相关担忧的注意力，减少认知性过度觉醒。
- 疗效证据：
- 适用人群与局限性：音乐疗法操作简便、成本低廉、无副作用，尤其适用于对药物敏感或不愿使用药物的轻中度失眠患者、大学生等群体。然而，其作为单一疗法对严重失眠的疗效可能有限，且并非所有类型的音乐都适合作为助眠工具，个体偏好也可能影响疗效。
3.3.2 针灸疗法
针灸作为一种传统中医技术，通过刺激特定穴位来调节身体功能，已被用于治疗包括失眠在内的多种疾病。
- 改善机制：针灸可能通过调节神经递质（如5-羟色胺、褪黑素）、平衡自主神经系统活动、降低皮质醇水平、改善脑电活动以及减轻焦虑和抑郁来促进睡眠 104。
- 疗效证据：
- 一项针对原发性失眠的随机对照试验发现，针灸治疗能显著改善失眠严重程度指数（ISI）、睡眠效率（SE）、总睡眠时间（TST）和抑郁评分（SDS），并且在治疗后2周和4周的随访中效果持续优于假针灸组 105。
- 对于伴有抑郁症的失眠患者，电针治疗显著改善了PSQI评分，并在24周随访中保持疗效，同时改善了抑郁、焦虑症状和总睡眠时间 106。
- 在癌症相关失眠方面，系统综述和荟萃分析显示，针灸对癌症患者的失眠有潜在益处，尤其对乳腺癌患者的PSQI评分有显著改善，且安全性良好 107108。对于接受化疗的乳腺癌患者，针灸治疗不仅能改善化疗相关的失眠，还能提高睡眠效率、总睡眠时间、入睡潜伏期，并减轻焦虑、抑郁，提高生活质量，甚至有助于减少安眠药的使用 109。
- 一项针对围绝经期抑郁和失眠患者的随机对照试验表明，针灸对改善PSQI评分具有短期和中期疗效，但对抑郁症状的改善不显著且长期效果有待进一步研究 110。
- 特殊形式：经皮耳迷走神经刺激（taVNS）作为一种非侵入性神经调节技术，也被证明对慢性失眠有效。一项随机临床试验显示，taVNS能显著降低PSQI评分，其效果优于假刺激组，且效果可持续20周，并能改善心理健康和疲劳 111。
- 适用人群与局限性：针灸适用于对药物治疗有顾虑、药物效果不佳或伴有其他共病（如慢性疼痛、癌症相关症状）的失眠患者。然而，针灸的疗效可能受操作者技术、穴位选择和治疗方案差异的影响。尽管报告的副作用轻微，但其对长期疗效和机制的深入研究仍需加强 104。
3.3.3 植物疗法与芳香疗法
一些天然植物提取物和精油也被用于辅助睡眠。
- 薰衣草：薰衣草（Lavender）精油因其镇静和放松特性而闻名，被广泛用于改善睡眠障碍。
- 疗效证据：一项综述指出，薰衣草对多种疾病患者（如癌症、终末期肾病、神经精神疾病）的睡眠障碍显示出有希望的疗效，其最常见的给药途径是吸入精油（芳香疗法）或结合按摩使用 112。
- 中草药：某些中草药制剂也被研究用于治疗失眠。
- 疗效证据：例如，舒眠胶囊（Shu Mian Capsule, SMC）作为一种商业中草药制剂，在合并失眠的抑郁症患者中，与精神药物联用能显著改善抑郁和睡眠质量，且副作用较少。然而，其作为常规抗抑郁治疗替代品的有效性尚不明确，且现有证据质量较低，需要更多严格的试验来验证 113。
- 适用人群与局限性：植物疗法和芳香疗法通常具有较好的耐受性，适合作为辅助性放松手段或对药物有禁忌的患者。但其作用机制尚需进一步阐明，且疗效的证据强度和一致性不如CBT-I和部分药物。使用者应注意产品质量，并警惕潜在的过敏反应。
3.3.4 辅助疗法的定位与整合
辅助疗法在失眠管理中扮演补充角色，而非替代一线治疗。
- 作为CBT-I的补充：对于难以入睡或难以放松的患者，音乐疗法、芳香疗法或放松训练可以作为CBT-I的辅助手段，帮助其更好地实践刺激控制和认知重构。
- 特殊人群的选择：对于特定人群，针灸等辅助疗法可能在减轻失眠的同时，改善特定伴随症状。例如，对于癌症患者，针灸已被证明可以改善癌症相关失眠107；对于围绝经期女性，针灸对改善围绝经期抑郁和失眠的PSQI评分具有短期和中期疗效110。
- 个体化选择：辅助疗法的选择应基于患者的偏好、可及性、共病情况和风险收益比。临床医生应在充分告知患者疗法特点、证据强度和潜在局限性的基础上，共同做出决策。
- 证据等级差异：患者和临床医生都应认识到，CBT-I作为失眠的一线治疗，其证据等级最高，其次是某些药物治疗。辅助疗法的证据等级通常较低，需要更多高质量的研究来验证其长期疗效和安全性。
总而言之，音乐疗法、针灸、植物疗法等辅助干预为失眠患者提供了多样化的治疗选择。它们可以通过不同的途径改善睡眠，尤其在减轻焦虑、促进放松和处理共病症状方面显示出潜力。然而，在临床实践中，应将其视为综合治疗方案的一部分，并强调其作为CBT-I补充而非替代的角色。
4.1 一线药物的分类与特点
当非药物干预（特别是CBT-I）效果不佳或不可及，或者患者症状严重需要快速缓解时，药物治疗可作为重要的干预手段 114。失眠药物种类繁多，其作用机制、疗效、安全性和耐受性各不相同。目前临床上常用的一线药物主要包括双食欲素受体拮抗剂（DORAs）、苯二氮䓬受体激动剂（BDZRA，包括苯二氮䓬类和Z-药物）以及褪黑素受体激动剂等 114。选择合适的药物应考虑患者的失眠类型（入睡困难或维持睡眠困难）、共病情况、潜在药物相互作用以及患者的偏好。
4.1.1 双食欲素受体拮抗剂（DORAs）
双食欲素受体拮抗剂（Dual Orexin Receptor Antagonists, DORAs）是一类较新的失眠治疗药物，通过阻断食欲素（Orexin/Hypocretin）的作用来促进睡眠。食欲素是下丘脑分泌的神经肽，在维持觉醒状态中发挥关键作用 115。DORAs通过可逆性地阻断食欲素受体（Orexin-1和Orexin-2），抑制食欲素系统的促觉醒信号，从而允许睡眠发生，这与传统镇静催眠药通过增强GABA抑制作用不同，被认为更接近生理性睡眠调节机制。
- 作用机制：食欲素能促进清醒，其活性过高被认为是失眠病理生理机制之一。DORAs通过竞争性结合并阻断食欲素受体，降低觉醒系统活性，从而促进睡眠的发生和维持。
- 代表药物：包括舒维雷生（Suvorexant）、莱博雷生（Lemborexant）和达利多雷生（Daridorexant）等。
- 特点与优势：
- 抑制觉醒，而非直接镇静：DORAs的作用方式是抑制过度觉醒，而不是像苯二氮䓬类药物那样普遍抑制中枢神经系统，因此其诱导的睡眠可能更接近生理性睡眠 116。
- 改善多种睡眠参数：研究显示DORAs能有效改善入睡潜伏期（SOL）、觉醒后总时间（WASO）和总睡眠时间（TST）117。与安慰剂相比，莱博雷生和达利多雷生在改善SOL、WASO和TST方面表现出更大的疗效，且耐受性良好 117。一项荟萃分析发现，DORAs在改善总睡眠时间、睡眠潜伏期和入睡后觉醒时间方面优于Z-药物和安慰剂，且其在所有药物中排名最佳 117。
- 戒断反应和依赖性风险较低：有研究指出，DORAs在停药后出现戒断症状和反跳性失眠的风险低于苯二氮䓬类药物和Z-药物，且成瘾性潜力较小。
- 长期使用安全性较好：DORAs可用于长期治疗（如长达3个月或更长时间），被认为具有良好的耐受性 114。一项研究指出，莱博雷生在长期治疗中（超过3个月）具有持续的疗效，其安全性与短期治疗的安全性相似 118。
- 局限性：尽管DORAs具有诸多优势，但仍可能引起嗜睡、头晕、恶心等副作用。其高昂的价格也限制了部分患者的使用。
4.1.2 苯二氮䓬受体激动剂（Benzodiazepine Receptor Agonists, BDZRA）
苯二氮䓬受体激动剂包括传统的苯二氮䓬类药物（如三唑仑、地西泮、劳拉西泮）和非苯二氮䓬类受体激动剂（俗称“Z-药物”，如唑吡坦、佐匹克隆、扎来普隆）。它们主要通过增强γ-氨基丁酸（GABA）在中枢神经系统中的抑制作用来发挥镇静催眠效果。
- 作用机制：BDZRAs结合GABA-A受体上的特定位点，增强GABA的效应，导致氯离子通道开放频率增加（苯二氮䓬类）或时间延长（Z-药物），使神经元超极化，从而抑制神经元兴奋性，产生镇静、催眠、抗焦虑、肌松和抗惊厥作用。
- 代表药物：
- 苯二氮䓬类：三唑仑（Triazolam）、替马西泮（Temazepam）、艾司唑仑（Estazolam）等。三唑仑因其短半衰期，在治疗入睡困难和夜间觉醒（MOTN）失眠方面有效，且不易影响精神运动能力 119。
- Z-药物：唑吡坦（Zolpidem）、佐匹克隆（Zopiclone）、扎来普隆（Zaleplon）。这些药物对GABA-A受体的α1亚基具有相对选择性，理论上副作用小于苯二氮䓬类，但仍存在相似的风险。
- 特点与优势：
- 起效快，疗效显著：BDZRAs能迅速缩短入睡潜伏期，减少夜间觉醒次数，提高睡眠效率，对急性失眠和短期失眠的疗效确切 118。
- 广泛可用性：这些药物上市时间较长，临床经验丰富，且价格相对较低。
- 局限性与风险：
4.1.3 褪黑素受体激动剂
褪黑素受体激动剂通过模拟内源性褪黑素的作用，调节昼夜节律和促进睡眠。
- 作用机制：这些药物主要作用于MT1和MT2褪黑素受体。MT1受体的激活与睡眠的启动和维持有关，而MT2受体的激活则参与昼夜节律的重新同步 122。
- 代表药物：包括雷美替胺（Ramelteon）和长效褪黑素（Prolonged-release melatonin）。阿戈美拉汀（Agomelatine）是另一类褪黑素受体激动剂，但主要用于抑郁症治疗，其催眠作用是次要的 123。
- 特点与优势：
- 局限性：
- 非处方褪黑素：需注意，市售的非处方褪黑素产品并非药物，其成分、剂量和纯度可能不规范，应谨慎使用，尤其是在老年人中，尚缺乏长期使用的安全性证据 128。
4.1.4 其他药物
- 低剂量镇静性抗抑郁药：如多塞平（Doxepin）和米氮平（Mirtazapine）等，其低剂量时通过阻断组胺H1受体产生镇静作用，可用于短期失眠治疗 114120。但这些药物主要作为非适应症使用，且可能存在抗胆碱能副作用，需注意。
- 抗精神病药物和抗组胺药：欧洲失眠指南不推荐使用抗精神病药物和抗组胺药治疗失眠，因为它们的疗效证据不足，且副作用较大 39114。
药物治疗应在医生指导下进行，通常建议短期使用（≤4周），且应定期评估疗效和安全性。对于慢性失眠，CBT-I仍是首选一线治疗，药物应作为辅助或短期缓解症状的手段。
4.2 特殊人群的药物调整策略
在失眠的药物治疗中，针对特殊人群，如老年人、孕妇和共病患者，需要采取更加谨慎和个体化的策略。这包括选择合适的药物、调整剂量以及严格控制用药时长，以最大程度地提高疗效并降低风险。
4.2.1 老年人（避免苯二氮䓬类）
老年人是失眠的高发人群，同时也是药物副作用的高风险群体。老年人由于年龄增长，对苯二氮䓬类药物的敏感性更高，更容易出现不良反应 129。
- 避免使用苯二氮䓬类药物（Benzodiazepines）：
美国老年医学会（American Geriatrics Society）等多个医学组织强烈建议老年人避免使用苯二氮䓬类药物或非苯二氮䓬类催眠药（Z-药物） 130。苯二氮䓬类药物在老年人中与跌倒、骨折、认知功能障碍（包括记忆力减退和谵妄）、日间嗜睡、药物依赖和戒断症状的风险显著增加有关 130。尽管如此，苯二氮䓬类药物仍被大量开给老年患者，这凸显了临床实践中需要改变用药模式 130。 - 优先推荐药物：
- 双食欲素受体拮抗剂（DORAs）：DORAs通过抑制觉醒来促进睡眠，而非诱导镇静，因其不诱导镇静且滥用潜力低，被认为是老年失眠患者的较优选择 131。莱博雷生（Lemborexant）等DORAs在老年人中表现出良好的疗效和耐受性 132。
- 褪黑素受体激动剂：雷美替胺（Ramelteon）和长效褪黑素（Prolonged-release melatonin）是老年失眠患者的另一安全选择。长效褪黑素已被批准用于55岁及以上失眠患者的短期治疗（最长3个月），其优势在于副作用少，不会引起依赖或戒断反应 114。
- 低剂量多塞平（Low-dose doxepin）：小剂量（如3-6mg）的多塞平作为一种选择性组胺H1受体拮抗剂，可以改善老年人的睡眠维持，且对认知功能影响较小 133。
- 用药原则：
- 低剂量起始：无论选择何种药物，老年患者均应从小剂量开始，并根据疗效和耐受性缓慢调整。
- 短期使用（≤4周）：药物治疗应以短期、按需使用为主，持续时间一般不应超过4周。
- 定期评估：治疗期间应密切监测患者的认知功能、平衡能力和日间嗜睡情况，并定期评估药物疗效和不良反应。
4.2.2 孕妇
孕期和哺乳期女性的失眠治疗具有特殊性，需要充分权衡药物对母婴的潜在风险。
- 药物选择的挑战：由于伦理限制，针对孕妇的药物临床试验较少，因此许多药物在孕期使用的安全数据不足。
- 褪黑素：目前来看，关于孕期和哺乳期使用外源性褪黑素的人类研究有限，但现有临床试验并未提示主要的安全问题或不良事件 134。尽管动物研究曾提出担忧，但人类研究的证据表明，孕期和哺乳期使用褪黑素可能是安全的 134。然而，由于缺乏针对失眠作为主要结局的随机对照试验，仍需谨慎。
- 三唑仑：鉴于其短半衰期，在某些特殊情况下，经医生评估后，可考虑短期、小剂量使用以解决严重的入睡困难，但须权衡风险与收益。
- 非药物干预优先：对于孕妇失眠，数字认知行为疗法（dCBT-I）被认为是有效、安全且可接受的干预措施，能显著改善孕期失眠症状 135。因此，非药物干预应是首选。
- 抗抑郁药：如果失眠与孕期抑郁症共病，抗抑郁药在孕期和哺乳期是相对安全的治疗选择，但需在医生指导下使用 136。
4.2.3 共病患者（如抑郁合并失眠）
失眠常常与精神疾病（如抑郁症、焦虑症）或躯体疾病共病，这种情况下，药物选择需考虑对两种疾病的协同作用，并避免潜在的药物相互作用。
- 抑郁合并失眠：
- 优先治疗原发病：对于抑郁症合并失眠的患者，首先应积极治疗抑郁症。许多抗抑郁药，特别是选择性5-羟色胺再摄取抑制剂（SSRIs）或5-羟色胺和去甲肾上腺素再摄取抑制剂（SNRIs），虽然可能在治疗初期加重失眠，但随着抑郁症状的改善，失眠也常随之缓解。
- 镇静性抗抑郁药：一些具有镇静作用的抗抑郁药（如曲唑酮Trazodone、米氮平Mirtazapine）可以在治疗抑郁症的同时改善失眠。曲唑酮（Trazodone）特别适用于睡眠维持困难的患者，它能增加深睡眠，且与嗜睡和体重增加的风险较低 137。然而，曲唑酮对于入睡困难的效果可能不如催眠药，且需要提前服用 137。
- CBT-I联合药物：认知行为疗法（CBT-I）联合抗抑郁药可能是最有效的治疗策略。CBT-I可以直接针对失眠症状，而抗抑郁药则治疗情绪障碍。
- 共病心血管疾病/慢性疼痛：
- 避免潜在风险药物：对于心血管疾病患者，应避免使用可能影响心律或血压的药物。对于慢性疼痛患者，苯二氮䓬类药物可能加重疼痛感或与止痛药产生不良相互作用。
- DORAs：DORAs因其选择性作用机制，对心血管功能影响较小，可能是这类患者的较好选择。
- 非药物干预：CBT-I和针对疼痛的非药物干预（如物理治疗、正念）应作为重要组成部分。
4.2.4 药物调整的普遍原则
- 低剂量起始：无论针对何种人群，均应从最低有效剂量开始。
- 短期使用（≤4周）：药物主要用于短期症状缓解，应避免长期依赖。欧洲指南建议苯二氮䓬类和Z-药物用于短期治疗（≤4周），而食欲素受体拮抗剂可用于长达3个月或更长时间，长效褪黑素在55岁以上患者中可使用长达3个月 114。
- 按需给药：在症状缓解后，可尝试按需给药而非每日给药，以减少药物暴露和依赖风险。
- 序贯或联合CBT-I：药物治疗应被视为CBT-I的辅助或桥梁，目标是最终过渡到以CBT-I为主的非药物管理。
- 停药策略：当需要停用药物时，尤其是苯二氮䓬类药物，应采取逐渐减量的方式，以避免戒断反应和反跳性失眠 130。有证据表明，直接针对患者的干预措施（如YAWNS-1方案）可以有效减少老年人对苯二氮䓬受体激动剂（BZRA）的长期使用，并改善睡眠结局 138。
总之，特殊人群的失眠药物治疗需要高度的临床判断和个体化策略。在老年人中应避免苯二氮䓬类药物；孕妇应优先选择非药物干预，并在权衡利弊后谨慎用药；共病患者则需考虑药物对两种疾病的影响及潜在的药物相互作用。低剂量起始、短期使用和定期评估是所有特殊人群药物治疗的基本原则。
4.3 药物联合与长期管理
失眠的药物治疗与非药物干预（尤其是CBT-I）并非相互排斥，而是可以相互补充，通过序贯或联合使用来优化治疗效果，实现长期管理。有效的整合策略能够最大化疗效，同时最小化药物相关风险。
4.3.1 CBT-I与药物的序贯/联合使用策略
目前关于CBT-I和药物治疗的最佳整合方式尚未形成统一标准，但现有研究提供了有价值的洞察 139。
序贯治疗：
- 药物先行，CBT-I 后续：对于急性失眠或症状严重、急需快速缓解的患者，可以短期（通常不超过4周）使用药物快速改善睡眠，随后引入CBT-I进行巩固和维持治疗，并逐步撤停药物。这种方法能够迅速缓解患者痛苦，为CBT-I的实施创造条件。然而，有研究提示，如果治疗序列从药物开始，后续引入CBT-I时，睡眠改善的主要部分往往发生在CBT-I引入之后 140。
- CBT-I 先行，药物按需：鉴于CBT-I作为一线治疗的地位，其长期疗效和安全性优势，通常建议优先启动CBT-I。在CBT-I治疗过程中，如果患者依从性不佳、疗效不明显或存在急性症状波动，可考虑按需短期使用药物作为辅助。这种策略有助于患者建立非药物性的应对机制，避免对药物的长期依赖。
- 药物与CBT-I交叠：一些研究探索了药物和CBT-I在一段时间内同时使用，随后撤停药物，仅保留CBT-I的策略。一项探索性研究发现，从药物与CBT-I联合治疗开始，然后过渡到单独CBT-I的序列，似乎能产生最佳的治疗效果 140。另一项研究也支持这种交叠的序贯治疗，即先使用药物5周，在第4周引入CBT，并在第5周后撤药，结果显示睡眠改善在CBT引入后更为显著 141。
联合治疗：
- 同步联合：在某些情况下，特别是对于慢性、难治性失眠或伴有严重共病（如重度抑郁症合并失眠）的患者，可能需要CBT-I与药物治疗同步进行。这种策略可能在短期内提供更强的疗效，因为药物能够快速缓解症状，而CBT-I则从根本上解决导致和维持失眠的行为和认知因素。然而，研究证据表明，CBT-I与药物联合使用在长期疗效上并不一定优于单独的CBT-I，且可能导致患者更多依赖药物，增加停药难度 139。因此，若采用联合治疗，应明确目标，并在症状稳定后逐步减少药物剂量直至停用。
- 特殊人群的联合：对于伴有精神疾病（如抑郁症、PTSD）的失眠患者，CBT-I联合抗抑郁药可能更有效。例如，CBT-I被证明可以改善患有抑郁症和失眠的患者的失眠严重程度，但其对抑郁症状的改善效果尚不明确 142。
4.3.2 长期用药的疗效持续性及潜在风险
虽然CBT-I被认为是慢性失眠的长期管理基石，但在某些情况下，患者可能需要长期药物治疗，特别是当非药物干预效果不佳或患者无法接受CBT-I时 143。长期用药的决策需要个体化权衡持续性失眠的风险与药物治疗的潜在风险和益处。
疗效持续性：
潜在风险：
- 耐受性（Tolerance）：长期使用苯二氮䓬类和Z-药物容易产生耐受性，即需要更高剂量才能达到相同的催眠效果 144147。这可能导致患者自行增加剂量，从而增加副作用和依赖性风险。
- 身体依赖性和戒断反应（Dependence and Withdrawal）：苯二氮䓬类和Z-药物的长期使用可导致身体依赖。突然停药可能引起戒断症状，包括反跳性失眠（比治疗前更严重的失眠）、焦虑、震颤、烦躁不安，甚至癫痫发作 145。DORAs和褪黑素受体激动剂的依赖性和戒断风险则显著较低。
- 不良事件：
- 相互作用：长期用药还需警惕药物间的相互作用，特别是对于同时服用多种药物的共病患者。例如，某些药物可能通过影响肝酶（如细胞色素P450系统）来改变失眠药物的代谢，从而增加副作用或降低疗效。
长期管理原则：
对于需要长期药物治疗的患者：
- 应优先选择依赖性、耐受性和戒断风险较低的药物，如DORAs。
- 定期评估药物疗效和安全性，权衡利弊。
- 尽可能使用最低有效剂量。
- 强调药物治疗是整体治疗方案的一部分，应与CBT-I或其他非药物干预相结合。
- 在条件允许时，应尝试在CBT-I的帮助下逐渐减量或停用药物。
- 告知患者药物的潜在风险和戒断症状，并提供停药指导。
总之，CBT-I与药物治疗的整合策略应根据患者的具体情况个体化制定。虽然药物可以快速缓解症状，但CBT-I是实现长期、可持续睡眠改善的关键。在长期药物管理中，应优先选择安全性更高、依赖性风险更低的药物，并密切监测疗效和副作用。
5. 特殊人群的精准管理策略
失眠的发生机制和临床表现在不同人群中存在显著差异，这要求针对性地制定精准管理策略。年龄、性别、共病情况等因素均会影响失眠的病理生理过程和治疗反应。因此，对特殊人群进行个体化干预是提高治疗效果的关键。
5.1 老年人群的失眠干预
老年人是失眠的高发群体，慢性失眠影响57%的美国老年人 133。虽然失眠不是衰老的正常组成部分，但随着年龄增长，睡眠模式会发生显著变化，包括入睡时间提前、夜间睡眠时间缩短、白天小睡频率增加、夜间觉醒次数和醒来时间增多，以及慢波睡眠（深睡眠）减少 149150151152。这些改变使得老年人更容易出现失眠症状，并且失眠与认知功能下降存在关联，例如睡眠效率的提高和入睡后觉醒时间的减少与更好的认知功能相关 153。此外，老年失眠往往与多种共病和药物使用相互交织，增加了管理的复杂性 6150。
5.1.1 关注年龄相关的睡眠结构改变
随着年龄增长，人体的昼夜节律系统和睡眠稳态机制变得不那么稳定 149151。内源性褪黑素分泌减少，且其分泌节律可能发生改变，导致睡眠-觉醒周期的紊乱。慢波睡眠（NREM睡眠的第三和第四阶段）是深度恢复性睡眠，在老年人中显著减少甚至消失 152。这不仅影响睡眠的恢复功能，还可能与认知功能下降有关。因此，在评估老年失眠患者时，应充分考虑这些生理性变化。
5.1.2 推荐以CBT-I为主的治疗策略
认知行为疗法（CBT-I）被广泛认为是老年人失眠的一线治疗金标准 669126154。其长期疗效优于药物治疗，且无药物相关的副作用。
- 长期疗效：多项研究表明，CBT-I在老年人中能显著改善失眠症状，包括入睡潜伏期、睡眠效率和总睡眠时间，并且这种改善可以维持较长时间 69。CBT-I不仅能有效治疗失眠，还能改善老年患者的认知功能和生活质量。
- 组分优势：CBT-I的核心组分，如刺激控制、睡眠限制和认知重构，对老年人同样有效。特别是睡眠限制疗法，通过缩短卧床时间以增加睡眠效率，对于因卧床时间过长而导致睡眠片段化的老年人尤为适用。
- 预防抑郁：针对老年人失眠的CBT-I干预还具有重要的公共卫生意义。一项随机临床试验显示，CBT-I在预防老年人发生首发或复发性重度抑郁症方面具有显著益处 155。这强调了在老年人群中推广CBT-I的必要性，不仅是为了改善睡眠，更是为了促进整体心理健康。
- 可及性：数字CBT-I（dCBT-I）的出现，为老年人提供了更便捷的CBT-I获取途径，克服了传统面对面治疗的可及性障碍。
5.1.3 谨慎使用药物与药物调整原则
尽管CBT-I是首选，但对于部分老年患者，当CBT-I效果不佳或不可及时，药物治疗仍是重要的补充手段。然而，由于老年人存在多重共病、药物代谢减慢、药物敏感性增加以及跌倒等风险，药物选择必须极其谨慎 6133150。
- 避免苯二氮䓬类药物和Z-药物：美国老年医学会等机构强烈建议老年人避免使用苯二氮䓬类药物（如三唑仑、替马西泮）和Z-药物（如唑吡坦、佐匹克隆） 69130。这些药物会增加老年人跌倒、骨折、认知功能障碍、日间嗜睡、精神错乱以及药物依赖的风险 130。一项伞形综述强调，苯二氮䓬类和Z-药物是老年人使用睡眠药物的最常见原因，但其危害大于益处 133。
- 优先考虑的药物：
- 双食欲素受体拮抗剂（DORAs）：如达利多雷生（daridorexant）和莱博雷生（lemborexant），因其通过抑制过度觉醒来促进睡眠，而不是直接镇静，滥用潜力低，对老年人可能是一个更安全有效的选择 126。
- 褪黑素受体激动剂：如雷美替胺（ramelteon）和长效褪黑素，副作用较少，不会引起依赖性或戒断反应，对老年人的耐受性良好。长效褪黑素已被推荐用于55岁及以上老年人的短期失眠治疗（最长3个月） 126128133。有研究显示，高剂量褪黑素（5mg）能增加老年人在夜间和白天睡眠期间的总睡眠持续时间 156。
- 低剂量多塞平（Low-dose doxepin）：作为一种抗组胺药，低剂量多塞平（如3-6mg）可用于改善老年人的睡眠维持，且对认知功能影响较小 126133。
- 用药原则：
- 低剂量起始：总是从最低有效剂量开始，并根据患者反应缓慢调整。
- 短期使用：药物治疗应尽量短期（≤4周），按需使用，避免长期依赖。
- 定期评估：密切监测药物的疗效和潜在副作用，尤其是认知功能、平衡和日间嗜睡。
- 逐步减量：当决定停药时，应采取逐渐减量的方式，以避免戒断症状和反跳性失眠 130。
5.1.4 结合昼夜节律调整（如光疗）改善睡眠效率
老年人的昼夜节律紊乱是失眠的重要原因之一，因此，通过光疗等方法调整昼夜节律，可以有效改善睡眠效率。
- 光疗：光照是调节昼夜节律的最强“时间线索”（zeitgeber）。适当的光照暴露，尤其是在早晨，可以帮助老年人重置生物钟，使其与外部环境同步，从而改善入睡时间和睡眠维持。光疗已被用于治疗昼夜节律睡眠-觉醒障碍，例如延迟睡眠时相障碍和不规则睡眠-觉醒节律障碍，这些障碍在老年人中也较常见 157158。
- 规律作息：除了光疗，保持规律的作息时间，包括固定的起床和睡觉时间，即使在周末也应尽量保持一致，对于稳定老年人的昼夜节律至关重要。
- 户外活动：白天适度的户外活动不仅能增加光照暴露，还能促进身体活动，有助于增强夜间的睡眠驱动力。
综上所述，老年失眠的精准管理应以CBT-I为核心，结合谨慎的药物使用原则和昼夜节律调整策略。这种多模式的综合干预方法，能够更有效地应对老年失眠的复杂性，改善睡眠质量，提升生活品质，并对认知功能起到积极的保护作用。
5.2 更年期女性的综合管理
更年期是女性生命中的一个特殊阶段，常伴随着一系列生理和心理变化，其中失眠是影响生活质量最常见的困扰之一。围绝经期和绝经后女性的失眠患病率显著高于同龄男性，高达35%-60%的绝经后女性会经历失眠 159。理解更年期失眠的特点及其与激素水平波动的关联，对于制定有效的综合管理策略至关重要。
5.2.1 分析雌激素下降与失眠的关联
更年期女性失眠的发生机制复杂，雌激素水平的下降被认为是核心因素之一 125160。
- 激素波动的影响：
- 雌激素：雌激素对中枢神经系统有广泛影响，包括调节睡眠结构、体温调节和情绪。围绝经期和绝经后，卵巢功能衰退导致雌激素水平波动并逐渐下降，这可能直接干扰睡眠调节机制。雌激素水平下降会减少快速眼动（REM）睡眠和慢波睡眠（深睡眠）的比例，导致睡眠碎片化和总睡眠时间减少 160。
- 潮热和盗汗：雌激素下降还会导致血管舒缩症状，即潮热和夜间盗汗（Vasomotor Symptoms, VMS）。VMS是导致更年期失眠的最主要原因之一，夜间潮热可引起频繁觉醒，严重干扰睡眠 125161。研究显示，约70%的女性在绝经后会出现潮热 162。
- 情绪障碍：雌激素水平的波动也与情绪不稳、焦虑和抑郁的发生密切相关 159161。焦虑和抑郁本身就是失眠的重要诱因和维持因素，形成恶性循环。
- 其他相关因素：
除了激素变化，更年期女性失眠还受到其他生物心理社会因素的影响，包括年龄增长、肥胖、慢性疼痛、睡眠呼吸暂停等共病，以及不良睡眠习惯、生活压力和对睡眠的担忧等 125。这些因素往往相互作用，进一步加剧失眠的严重程度。
5.2.2 讨论激素替代疗法（HRT）的适用场景
激素替代疗法（Hormone Replacement Therapy, HRT）通过补充雌激素（有时联合孕激素）来缓解更年期症状，对改善与雌激素缺乏相关的失眠具有潜在益处。
- 改善潮热相关失眠：HRT在改善潮热和盗汗方面效果显著，通过减少这些血管舒缩症状，从而减少夜间觉醒，改善睡眠质量 125。对于以潮热为主要困扰并导致失眠的女性，HRT是有效的治疗选择。
- 直接改善睡眠：有研究表明，HRT可以直接改善绝经后女性的睡眠模式。例如，雌激素联合孕激素治疗比单独使用雌激素更能有效减少周期性肢体运动（PLM）的发生率、潮热和夜间磨牙症，同时也能改善呼吸不规则、睡眠觉醒、焦虑和记忆障碍等问题 163。但也有研究认为，HRT对睡眠质量的改善主要是通过缓解血管舒缩症状间接实现的，其本身作为改善睡眠障碍的主要证据尚不充分 159。
- 适用人群与风险权衡：
- 适应症：HRT主要适用于潮热等更年期症状严重，且无HRT禁忌症的绝经期女性。
- 个体化评估：在考虑HRT时，必须进行个体化的风险效益评估，包括乳腺癌、心血管疾病和血栓形成的风险 125。目前指南建议在更年期早期（通常指绝经后10年内或60岁之前）且无禁忌症的女性中使用HRT，且应使用最低有效剂量，最短有效疗程。
- 禁忌症：有乳腺癌史、血栓栓塞史、不明原因阴道出血或严重肝肾功能不全等情况的女性禁用HRT。
- 证据局限：尽管有研究支持HRT在改善更年期失眠中的作用，但目前对于将其作为治疗更年期睡眠障碍的独立疗法的具体证据仍缺乏一致性 159164。欧洲妇科内分泌学会（ESG）的建议指出，当失眠是更年期潮热和/或盗汗的症状时，HRT可能会有效 125。
5.2.3 结合认知行为干预缓解潮热、焦虑等伴随症状
鉴于HRT的适用限制和潜在风险，非药物干预，特别是认知行为疗法（CBT），在更年期女性失眠管理中扮演着核心角色。CBT不仅直接针对失眠，还能有效缓解潮热、焦虑和抑郁等伴随症状 165。
- 认知行为疗法（CBT-I）：
- 辅助疗法：
- 睡眠卫生和生活方式调整：
- 规律作息：保持固定的睡眠-觉醒时间，即使在周末也要尽量保持一致。
- 环境优化：保持卧室凉爽、黑暗、安静，有助于减少夜间潮热的干扰。
- 避免刺激物：睡前避免咖啡因、酒精和尼古丁。
- 规律运动：适度规律的运动有助于改善睡眠，但应避免睡前剧烈运动。
- 饮食调整：避免辛辣食物，可能有助于减少潮热的发生。
综上所述，更年期女性的失眠管理应采取多模式、个体化的方法。对于伴有严重潮热症状的女性，在全面评估风险后，HRT可能是一个有效的选择。然而，认知行为疗法，包括针对失眠的CBT-I和针对潮热的CBT-VMS，以及其他辅助身心疗法，应作为更年期女性失眠管理的核心和基础，以综合改善睡眠质量和整体生活质量。
5.3 共病与高风险人群的协同治疗
失眠作为一种普遍的共病现象，常常与多种躯体和精神疾病并存，并对原发病的进展和预后产生负面影响。因此，对于共病和高风险人群，需要采取“失眠-原发病”双靶点的协同治疗模式，以期同时改善失眠和原发疾病，从而提高患者的整体健康水平和生活质量。
5.3.1 PTSD、癌症、心血管疾病等共病患者的失眠特点
创伤后应激障碍 (PTSD) 合并失眠：
睡眠障碍和噩梦是PTSD的核心症状，且与PTSD的发生发展密切相关 57。PTSD患者常报告睡眠质量差、入睡困难、睡眠维持困难、夜间焦虑、噩梦和应激性梦境 57。这种失眠不仅影响患者日间功能，还可能阻碍PTSD的治疗效果 169。PTSD与失眠之间的关系是双向的，持续的睡眠障碍可能影响疾病进程 57。军人及退伍军人是PTSD的高风险人群，因此其失眠问题尤为突出 170。癌症患者合并失眠：
癌症相关失眠是癌症患者常见的症状负担，显著影响其生活质量 65。其原因复杂多样，包括癌症本身引起的疼痛、恶心、疲劳、呼吸困难等症状，以及化疗、放疗等治疗带来的副作用，还有对疾病预后的心理压力、焦虑和抑郁 65。某些癌症（如肺癌、乳腺癌、头颈部肿瘤）患者的失眠尤为常见，且老年女性癌症患者似乎更易感 65。心血管疾病 (CVD) 合并失眠：
越来越多的证据表明，失眠是心血管疾病（如冠心病、心房颤动、心力衰竭、心肌梗死、高血压和卒中）的独立风险因素 171。失眠可能通过激活交感神经系统、炎症反应、内皮功能障碍以及影响血压调节等机制，增加心血管事件的风险 171。一项系统性荟萃分析表明，失眠可能与冠心病、心房颤动、心力衰竭、高血压和卒中存在因果关系 171。
5.3.2 “失眠-原发病”双靶点干预模式
针对这些高风险共病人群，单一治疗往往不足以解决复杂的问题，因此需要采取整合性的“失眠-原发病”双靶点干预模式。
认知行为疗法（CBT-I）作为核心干预：
CBT-I作为失眠的一线治疗，在共病情况下仍显示出强大的有效性。- PTSD：CBT-I被证实能够有效改善PTSD患者的失眠症状 172。研究表明，将CBT-I与创伤暴露疗法（如延长暴露疗法PE）相结合（如2NITE方案），能够显著改善失眠和PTSD症状，提高生活质量 173。这种整合治疗对减少PTSD患者的失眠严重程度和PTSD症状都显示出显著效果 170172。虽然CBT-I对于改善PTSD患者的噩梦症状效果不一，但对于整体睡眠紊乱的改善作用显著 172174。
- 癌症：CBT-I对癌症患者的失眠具有显著疗效 65。
- 抑郁和焦虑：CBT-I在改善共病抑郁症或焦虑症患者的失眠症状方面表现出色 56142。一项荟萃分析发现，CBT-I在伴有抑郁症、PTSD和酒精依赖的患者中，对失眠严重程度的改善效果达到中度至高度效应量 56。虽然CBT-I对共病精神疾病症状本身的改善效果存在争议，但对失眠的显著改善可以间接减轻这些精神疾病的负担 56142。
CBT-I联合药物治疗：
在某些共病情况下，CBT-I与药物治疗的联合或序贯使用可以实现更优的治疗效果。- PTSD：虽然CBT-I是首选，但对于伴有顽固性噩梦的PTSD患者，可能需要药物干预。盐酸哌唑嗪（Prazosin）是一种α1-肾上腺素受体拮抗剂，被广泛用于治疗PTSD相关的噩梦，并显示出改善睡眠质量的效果 172175。研究表明，哌唑嗪与CBT-I联合使用时，可能对PTSD症状和睡眠问题有协同作用。对于PTSD共病失眠，非苯二氮䓬类催眠药（如唑吡坦）虽然短期有效，但由于依赖性和副作用风险，应谨慎使用，且CBT-I仍是首选 176。
- 抑郁合并失眠：对于重度抑郁症合并严重失眠的患者，在CBT-I的基础上联合使用具有镇静作用的抗抑郁药（如曲唑酮）或短期的非苯二氮䓬类催眠药，可以更快地缓解症状。然而，应警惕苯二氮䓬类药物的潜在风险 177。研究指出，CBT-I能够显著改善抑郁症患者的睡眠质量，但对抑郁症状本身的改善效果较小 172。
针对原发病的特异性干预：
除了直接治疗失眠，还需积极治疗原发共病。- OSA：如果失眠患者合并阻塞性睡眠呼吸暂停（OSA），持续气道正压通气（CPAP）是OSA的一线治疗。虽然CPAP可能部分改善失眠症状，但对于共病性失眠和睡眠呼吸暂停（COMISA）患者，单纯CPAP治疗可能不足以完全解决失眠问题，需要将CBT-I与CPAP联合使用 169。
- 慢性肾病 (CKD)：CKD患者中失眠患病率高，且常伴有不宁腿综合征（RLS）、OSA等其他睡眠障碍 178。针对RLS的治疗（如铁剂补充、多巴胺受体激动剂）以及对OSA的CPAP治疗，对改善CKD患者的失眠至关重要 178。
- 慢性疼痛：对于慢性疼痛合并失眠的患者，疼痛管理（如物理治疗、止痛药物、局部注射）与CBT-I的结合是必要的。CBT-I不仅能改善睡眠，还能通过认知重构和放松训练减轻疼痛感知，打破疼痛-失眠的恶性循环。
- 心血管疾病：管理心血管疾病的失眠，除了CBT-I和谨慎的药物选择外，还需要积极控制心血管风险因素，如血压、血糖、血脂等。
5.3.3 降低失眠对原发病进展的影响
失眠对共病的负面影响是多方面的：
- 精神疾病：失眠会加重抑郁、焦虑和PTSD的症状，增加复发风险。有效治疗失眠可以改善这些精神疾病的整体预后 56142。
- 躯体疾病：失眠会增加癌症患者的症状负担，甚至可能加速心血管疾病的进展 65171。例如，对失眠的有效干预可能有助于降低心血管疾病的风险 171。
- 生活质量：无论何种共病，失眠都会显著降低患者的生活质量、功能状态和社会参与度。
因此，实施“失眠-原发病”双靶点干预模式，不仅能够直接改善失眠症状，还能通过减少失眠对原发病的负面影响，从而在长期内改善患者的整体健康状况，提高生活质量。这需要临床医生具备多学科知识，并能够协调不同治疗方案的实施。
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参考文献
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Insomnia disorder is characterized by chronic dissatisfaction with sleep quantity or quality that is associated with difficulty falling asleep, frequent nighttime awakenings with difficulty returning to sleep, and/or awakening earlier in the morning than desired. Although progress has been made in our understanding of the nature, etiology, and pathophysiology of insomnia, there is still no universally accepted model. Greater understanding of the pathophysiology of insomnia may provide important information regarding how, and under what conditions, the disorder develops and is maintained as well as potential targets for prevention and treatment. The aims of this report are (1) to summarize current knowledge on the pathophysiology of insomnia and (2) to present a model of the pathophysiology of insomnia that considers evidence from various domains of research. Working within several models of insomnia, evidence for the pathophysiology of the disorder is presented across levels of analysis, from genetic to molecular and cellular mechanisms, neural circuitry, physiologic mechanisms, sleep behavior, and self-report. We discuss the role of hyperarousal as an overarching theme that guides our conceptualization of insomnia. Finally, we propose a model of the pathophysiology of insomnia that integrates the various types of evidence presented.
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Insomnia, or the dissatisfaction with the quantity, quality or timing of sleep, is a common complaint. Because the definition of "normal" sleep is not well established, the estimates of the prevalence and severity of insomnia vary widely. Insomnia is often secondary to underlying psychiatric and medical conditions, and these should be evaluated and treated as a first measure. Nonpharmacological interventions for insomnia including sleep hygiene manoeuvres and exercise are recommended, although the success of these interventions has not been well documented. Benzodiazepines have been the pharmacologic agents of choice for the treatment of insomnia, but there is reason to exercise caution with their use; their overall benefit compared with placebo appears to be minor, and they are often associated with adverse cognitive effects. Unfortunately, no other class of drugs has proven to be superior to the benzodiazepines in terms of benefit:risk ratio. Given the importance of sleep for health and normal daily functioning the diagnosis, prognosis and treatment of insomnia should be a research priority.
3Prevalence of insomnia in a general adult population cohort using different diagnostic criteria: The seventh survey of the Tromsø study 2015-2016.PubMed
Kate Porcheret, Laila A Hopstock, Kristian Bernhard Nilsen
Sleep Med. 2024 Jul;119:289-295. doi: 10.1016/j.sleep.2024.05.002. Epub 2024 May 3.
Insomnia disorder is a subjective complaint of sleep dissatisfaction including both night-time and daytime symptoms. Currently there are three commonly used diagnostic manuals each with their own set of criteria, which is often credited for the wide range in insomnia prevalence reported by population-based studies, especially those with self-reported insomnia. However, there are limited studies directly comparing different criteria and little is known about associations with health outcomes. Thus, the aim of this study was to compare the most commonly used diagnostic criteria for insomnia from the literature and to explore the associations with a range of physical and mental health outcomes. We used data from 21,083 women and men from the seventh survey of the population-based Tromsø Study which included adults aged 40-99 years. A revised version of the Bergen Insomnia Scale was used to define insomnia based on the 4th (revised) and 5th edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR and DSM5), the 10th edition of the International Classification of Diseases (ICD-10), and the 3rd edition of the International Classification of Sleep Disorders (ICSD-3). We found the following prevalence of insomnia: DSM-IV-TR 23.6 %, DSM5 8.5 %, ICD-10 9.9 % and ICSD-3 20.0 %. When looking at each symptom, we found over half the participants classified as having insomnia using the DSM-IV-TR and ICSD-3 criteria did not report having impaired daytime functioning at least three days per week. Overall, participants with DSM5 and ICD-10 insomnia appeared to have worse health profiles, based on a higher percentage meeting the cut-off for possible anxiety or depression, reporting a psychological problem or chronic pain, and using antidepressants, painkillers or sleeping pills. However logistic regression models showed largely the same health factors had the same association with the odds for being classified as having insomnia disorder from each set of criteria. Overall, this study suggests that insomnia prevalence may be overestimated if daytime symptoms are not adequately included in accordance with current guidelines.
4Advancement in the contemporary clinical diagnosis and treatment strategies of insomnia disorder.PubMed
Soumi Paul, Karavadi Vidusha, Sivasudha Thilagar, et al.
Sleep Med. 2022 Mar;91:124-140. doi: 10.1016/j.sleep.2022.02.018. Epub 2022 Mar 1.
This review is intended to provide an updated summary of, but not limited to, classification, etiopathogenesis, diagnosis, and treatment strategies for insomnia disorder. The severity of insomnia symptoms irrespective of co-existing primary medical condition/s in the studied patients classified insomnia as 'insomnia disorder' to prioritize the clinical attention on insomnia (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition). The frequency and duration of symptoms further divided insomnia into chronic, short-term, and other insomnia disorder (International Classification of Sleep Disorders, Third Edition). This disorder is a phenomenal state of hyperarousal developed and perpetuated by environmental, behavioral, cognitive, genetic, socioeconomic, preexisting medical factors. Overarching physiological, cortical, behavioral, and cognition changes in hyperarousal manifest insomnia disorder. It, sometimes, leads to the co-occurrence of other chronic medical condition/s. The contemporary diagnosis of insomnia disorder needs to consider modified diagnostic criteria, growing evidence on insomnia disorder symptoms, associated factors, co-existing medical condition/s (if any) to identify the subjective severity of insomnia disorder and design a treatment plan. The recommended treatment strategies include cognitive-behavioral therapy for insomnia (CBTI) and pharmacotherapy. However, CBTI lacks accessibility, qualified facilitators, and pharmacotherapy has limitations like side effects, physiological tolerance/dependence. The investigation of phytocompounds subdued these drawbacks of existing treatments as some compounds showed anti-insomniac potential. Furthermore, complementary alternative medicines (CAMs) like mindfulness-based practices, acupuncture, listening to music, Yogasanas, Pranayama, digital cognitive behavioral therapy for insomnia (dCBTI) during bedtime proved supportive in insomnia disorder treatment.
5[Insomnia disorder].PubMed
Motohiro Ozone, Ayako Kuroda
Nihon Rinsho. 2015 Jun;73(6):924-8.
The rate of those who have sleep problems increases due to aging. In Japan, a super-aging society, insomnia is a common disease. It is reported that the ratio of insomniacs over sixty year-old is 29.5 %. The sleep disturbance in the elderly is caused by multi factors, such as physiological, physical, psychosociological, psychiatric, and pharmacological factors. According to the latest diagnostic criteria of sleep disorders, ICSD-3, the concept of primary or secondary insomnia was abolished. Instead of that, insomnia is categorized by the duration of disease, and general doctors can diagnose sleep disorders more easily than the past. However, it is not necessary to consider the pathophysiological mechanism, there is a concern that the clinical level of insomnia treatment might decline in quality.
6Common Sleep Disorders Affecting Older Adults.PubMed
Ecler Ercole Jaqua, Mary Hanna, Wessam Labib, et al.
Perm J. 2023 Mar 15;27(1):122-132. doi: 10.7812/TPP/22.114. Epub 2022 Dec 12.
Sleep disorders in older adults increase with aging, likely due to increased sleep latency, decreased sleep efficiency, and total sleep time. Common sleep issues include chronic insomnia, circadian rhythm sleep-wake disorders, sleep-related movement disorders, and sleep-disordered breathing. Diagnostic tools, such as a comprehensive sleep history and questionnaires, or a sleep log for more specific complaints, are commonly used. Polysomnography is not recommended as a routine test; however, it can be used for abnormal behaviors during sleep or if treatment fails. Sleep disorder management is based on the etiology and may include nonpharmacological and pharmacological alternative treatments. For example, nonpharmacological management for chronic insomnia and some sleep disorders may consist of cognitive behavioral therapy, sleep hygiene education, relaxation therapy, sleep restriction, light therapy, and stimulus control therapy. Because the quality of evidence for pharmacological treatment is poor, the medication choice should be based on shared decision-making between the practitioner and the patient, with limited prescription.
7Chronic insomnia, REM sleep instability and emotional dysregulation: A pathway to anxiety and depression?PubMed
Dieter Riemann, Raphael J Dressle, Fee Benz, et al.
J Sleep Res. 2025 Apr;34(2):e14252. doi: 10.1111/jsr.14252. Epub 2024 May 29.
The world-wide prevalence of insomnia disorder reaches up to 10% of the adult population. Women are more often afflicted than men, and insomnia disorder is a risk factor for somatic and mental illness, especially depression and anxiety disorders. Persistent hyperarousals at the cognitive, emotional, cortical and/or physiological levels are central to most theories regarding the pathophysiology of insomnia. Of the defining features of insomnia disorder, the discrepancy between minor objective polysomnographic alterations of sleep continuity and substantive subjective impairment in insomnia disorder remains enigmatic. Microstructural alterations, especially in rapid eye movement sleep ("rapid eye movement sleep instability"), might explain this mismatch between subjective and objective findings. As rapid eye movement sleep represents the most highly aroused brain state during sleep, it might be particularly prone to fragmentation in individuals with persistent hyperarousal. In consequence, mentation during rapid eye movement sleep may be toned more as conscious-like wake experience, reflecting pre-sleep concerns. It is suggested that this instability of rapid eye movement sleep is involved in the mismatch between subjective and objective measures of sleep in insomnia disorder. Furthermore, as rapid eye movement sleep has been linked in previous works to emotional processing, rapid eye movement sleep instability could play a central role in the close association between insomnia and depressive and anxiety disorders.
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Faizul Hasan, Amelia Nur Vidyanti, Pei-Shan Tsai, et al.
Sleep Breath. 2023 Oct;27(5):2013-2020. doi: 10.1007/s11325-023-02797-1. Epub 2023 Feb 28.
BACKGROUND: No study has examined the psychometric properties of the sleep condition indicator (SCI) for screening poststroke insomnia in the Indonesian population. We aimed to develop the Indonesian version of the sleep condition indicator (ISCI) and to examine its psychometric properties for screening adult patients in late sub-acute and chronic periods after stroke. METHODS: This was a cross-sectional study with two stages. In the first stage, the English version of the SCI was translated into the ISCI using standard procedures. The psychometric properties of the ISCI were tested in the second stage. Internal consistency and test-retest reliability of ISCI were used to evaluate reliability. A confirmatory factor analysis (CFA) was performed to test construct validity. To test concurrent and convergent validity, the Indonesian version of the insomnia severity index (ISI-INA), generalized anxiety disorder questionnaire (IGAD-7), and patient health questionnaire (IPHQ-9) were used. A receiver operating characteristic (ROC) analysis was conducted to calculate the optimal cutoff score of the ISCI on the basis of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for insomnia. RESULTS: A total of 160 adults with a diagnosis of stroke for more than 3 months were included (median age of 58.5 years, 31% met the DSM-5 criteria for insomnia). The ISCI had a satisfactory Cronbach's alpha of 0.89 and test-retest reliability of 0.78. The CFA revealed that the ISCI exhibited a satisfactory model fit and was associated with the ISI-INA, IGAD-7, and IPHQ-9 (r = -0.81, -0.32, and -0.52, respectively; all P < .001). The ROC test revealed that the optimal cutoff point of ≤23 yielded the highest sensitivity (94%) and specificity (97%). CONCLUSION: The study results revealed that the 8-item ISCI is a reliable and valid screening tool for detecting insomnia symptoms according to the DSM-5 criteria in the chronic period after stroke.
9The prevalence of insomnia in the general population in China: A meta-analysis.PubMed
Xiao-Lan Cao, Shi-Bin Wang, Bao-Liang Zhong, et al.
PLoS One. 2017 Feb 24;12(2):e0170772. doi: 10.1371/journal.pone.0170772. eCollection 2017.
UNLABELLED: This is the first meta-analysis of the pooled prevalence of insomnia in the general population of China. A systematic literature search was conducted via the following databases: PubMed, PsycINFO, EMBASE and Chinese databases (China National Knowledge Interne (CNKI), WanFang Data and SinoMed). Statistical analyses were performed using the Comprehensive Meta-Analysis program. A total of 17 studies with 115,988 participants met the inclusion criteria for the analysis. The pooled prevalence of insomnia in China was 15.0% (95% Confidence interval [CI]: 12.1%-18.5%). No significant difference was found in the prevalence between genders or across time period. The pooled prevalence of insomnia in population with a mean age of 43.7 years and older (11.6%; 95% CI: 7.5%-17.6%) was significantly lower than in those with a mean age younger than 43.7 years (20.4%; 95% CI: 14.2%-28.2%). The prevalence of insomnia was significantly affected by the type of assessment tools (Q = 14.1, P = 0.001). The general population prevalence of insomnia in China is lower than those reported in Western countries but similar to those in Asian countries. Younger Chinese adults appear to suffer from more insomnia than older adults. TRIAL REGISTRATION: CRD 42016043620.
10Sleep disorders in the elderly: a growing challenge.PubMed
Kamalesh K Gulia, Velayudhan Mohan Kumar
Psychogeriatrics. 2018 May;18(3):155-165. doi: 10.1111/psyg.12319.
In contrast to newborns, who spend 16-20 h in sleep each day, adults need only about sleep daily. However, many elderly may struggle to obtain those 8 h in one block. In addition to changes in sleep duration, sleep patterns change as age progresses. Like the physical changes that occur during old age, an alteration in sleep pattern is also a part of the normal ageing process. As people age, they tend to have a harder time falling asleep and more trouble staying asleep. Older people spend more time in the lighter stages of sleep than in deep sleep. As the circadian mechanism in older people becomes less efficient, their sleep schedule is shifted forward. Even when they manage to obtain 7 or 8 h sleep, they wake up early, as they have gone to sleep quite early. The prevalence of sleep disorders is higher among older adults. Loud snoring, which is more common in the elderly, can be a symptom of obstructive sleep apnoea, which puts a person at risk for cardiovascular diseases, headaches, memory loss, and depression. Restless legs syndrome and periodic limb movement disorder that disrupt sleep are more prevalent in older persons. Other common medical problems of old age such as hypertension diabetes mellitus, renal failure, respiratory diseases such as asthma, immune disorders, gastroesophageal reflux disease, physical disability, dementia, pain, depression, and anxiety are all associated with sleep disturbances.
11Worldwide prevalence of sleep problems in community-dwelling older adults: A systematic review and meta-analysis.PubMed
Jaquelini Betta Canever, Gabriela Zurman, Felipe Vogel, et al.
Sleep Med. 2024 Jul;119:118-134. doi: 10.1016/j.sleep.2024.03.040. Epub 2024 Apr 5.
The understanding of the prevalence of sleep problems in older adults can provide a broad and reliable perspective into the occurrence of such issues among older adults. This systematic review and meta-analysis aimed to estimate the worldwide prevalence of sleep problems in community-dwelling older adults. Studies that provide information on the prevalence of sleep problems in community-dwelling older adults (≥60 years) were screened between December 2022 and March 2023. A total of 20,379 studies were identified in database searches, from which 252 were included in this review. These studies covered the last 35 years (from 1988 to 2023) and pooled a sample of 995,544 participants from 36 countries. The most frequent sleep problem worldwide was obstructive sleep apnea (46.0%), followed by poor sleep quality (40.0%), other sleep problems (37.0%), insomnia (29.0%), and excessive daytime sleepiness (19.0%). No significant difference in the prevalence estimates of all sleep problems was observed between the sexes. This systematic review and meta-analysis showed a high prevalence of some sleep problems, mainly obstructive sleep apnea, poor sleep quality, and other sleep problems. Our estimates can be useful for managers and policymakers in planning healthcare strategies for sleep problems aimed at the older population.
12Insomnia and hot flashes.PubMed
Enrica Bonanni, Alessandro Schirru, Maria Caterina Di Perri, et al.
Maturitas. 2019 Aug;126:51-54. doi: 10.1016/j.maturitas.2019.05.001. Epub 2019 May 14.
The increased prevalence of sleep disorders associated with menopause has been emphasized by multiple international studies. Many factors are associated with insomnia during menopause, among them: hot flashes (HF), anxiety and depression, other medical conditions, behavioral and psychosocial factors and primitive sleep patterns. The domino hypothesis connects various factors and suggests that HF disturb sleep, thereby causing insomnia, which in turn increases vulnerability to depression. Nevertheless, sleep disorders predict mood disturbances more robustly than vasomotor symptoms (VMS), indicating that sleep also influences mood via other mechanisms. The medical conditions that may compromise sleep in this age group are common; they include obesity, gastroesophageal reflux, cancer, urinary incontinence and nocturia, thyroid dysfunction, chronic pain, fibromyalgia (often starting or worsening in menopause), and hypertension. Common causes of sleep disorders in middle-aged women include poor sleep hygiene, volitional factors, environmental disturbances, alcohol intake, marital dissatisfaction, requests for care from children, grandchildren and/or elderly parents, and financial worries. Evidence from other populations suggests that if insomnia is not treated, it may negatively affect the outcome of comorbid conditions. Taken together, these observations suggest that insomnia should be considered a disorder requiring specific attention and treatment. Moreover, recent cross-sectional data link sleep with subclinical markers of cardiovascular risk. It should also be noted that insomnia is common in patients with mild to moderate obstructive sleep apnea syndrome (OSAS).
13Women and insomnia.PubMed
Ellen Hirschman Miller
Clin Cornerstone. 2004;6 Suppl 1B:S8-18.
The occurrence of insomnia in women is influenced in great part by the complex hormonal cycles they undergo. Patterns of insomnia in younger women may be physiologically different on a hormonal basis from those found in older women. Although significant objective sleep disturbances have been difficult to demonstrate across the menstrual cycle in normal women, the International Classification of Sleep Disorders (ICSD) includes premenstrual insomnia and premenstrual hypersomnia as sleep disorders within the category of menstrual-associated sleep disorder. On the other hand, during pregnancy and after childbirth, profound fluctuations in steroid and hypothalamic-pituitary-adrenal axis-related hormones produce significant physiological changes, including sleep disruption. During the menopausal transition, significant sleep disruptions are provoked by sleep-disordered breathing, vasomotor disturbance, and mood disorders. Regardless of age, women with chronic insomnia are at higher risk for developing or sustaining depression. Thoughtful management approaches must consider known relationships between menstrual or menopausal status and various sleep disorders, and should rely on pharmacologic, nonpharmacologic, or a combination of treatments to achieve successful relief from insomnia. The off-label, first-line use of antidepressants for treating insomnia in the absence of depression is now considered debatable. The long-term efficacy and safety of the newer benzodiazepine receptor agonists (BZRAs) for insomnia, whether taken nightly or episodically, are supported by existing clinical experience. US Food and Drug Administration guidelines limiting the use of hypnotics to only a few weeks predate the newer generation BZRAs, and, as such, the guidelines may no longer be truly appropriate for these new agents.
14Prevalence of poor sleep quality during menopause: a meta-analysis.PubMed
Yu Jia, Zitong Zhou, Xuehua Cao
Sleep Breath. 2024 Dec;28(6):2663-2674. doi: 10.1007/s11325-024-03132-y. Epub 2024 Aug 15.
PURPOSE: Numerous researches have demonstrated that sleep quality deteriorates during menopause, but the prevalence rates vary between studies. The purpose of this meta-analysis was to determine the pooled prevalence of poor sleep quality during menopause and to explore potential moderators of discrepancies in prevalence between studies. METHODS: Web of Science, PubMed, PsycINFO and Embase databases were comprehensively searched from database creation to June 19, 2024. Studies were included if they focused on menopausal women and provided an estimate of the prevalence of poor sleep quality, which could be derived from the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Totally, 37 studies with 29,284 menopausal women were included in the analysis. A meta-analysis based on a random-effects model revealed that the prevalence of poor sleep quality during menopause was 50.8% (95% CI: 45.4-56.3%). The PSQI score was 6.24 (95% CI: 5.73-6.75). Subgroup analyses indicated that cut-off values of PSQI, menopausal status, age range, depressive symptoms and geographic region moderated the prevalence of poor sleep quality. Meta-regression analyses indicated that quality score was negatively correlated with the pooled prevalence. CONCLUSIONS: Poor sleep quality is a prevalent phenomenon among women during menopause. In light of the numerous adverse effects of poor sleep quality on menopausal women, it is of paramount importance to assess sleep quality on a regular basis and to implement effective interventions for menopausal women.
15Insomnia overview: epidemiology, pathophysiology, diagnosis and monitoring, and nonpharmacologic therapy.PubMed
Julie A Dopheide
Am J Manag Care. 2020 Mar;26(4 Suppl):S76-S84. doi: 10.37765/ajmc.2020.42769.
Insomnia, whether short-term or chronic, is a common condition. It has a negative impact on vulnerable patient groups, including active military personnel and veterans, patients with coexisting psychiatric and medical disorders, those in life transitions such as menopause, and elderly persons. Although cognitive behavioral therapy for insomnia (CBTI) is first-line treatment for insomnia, its high cost and a lack of trained providers has prevented widespread uptake. Now, digital CBTI (dCBTI) is emerging as a scalable option with the potential to overcome these barriers in managed care. The first part of this article reviews the epidemiology and pathophysiology of insomnia with a focus on vulnerable patient groups. The second part explores the rapidly evolving landscape of nondrug therapy for insomnia. The underlying concepts and supporting evidence for CBTI and dCBTI are presented, including their utility in vulnerable patient groups.
16The Management of Chronic Insomnia Disorder and Obstructive Sleep Apnea: Synopsis of the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guidelines.PubMed
Vincent Mysliwiec, Jennifer L Martin, Christi S Ulmer, et al.
Ann Intern Med. 2020 Mar 3;172(5):325-336. doi: 10.7326/M19-3575. Epub 2020 Feb 18.
DESCRIPTION: In September 2019, the U.S. Department of Veterans Affairs (VA) and the U.S. Department of Defense (DoD) approved a new joint clinical practice guideline for assessing and managing patients with chronic insomnia disorder and obstructive sleep apnea (OSA). This guideline is intended to give health care teams a framework by which to screen, evaluate, treat, and manage the individual needs and preferences of VA and DoD patients with either of these conditions. METHODS: In October 2017, the VA/DoD Evidence-Based Practice Work Group initiated a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature, created three 1-page algorithms, and advanced 41 recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. RECOMMENDATIONS: This synopsis summarizes the key recommendations of the guideline in 3 areas: diagnosis and assessment of OSA and chronic insomnia disorder, treatment and management of OSA, and treatment and management of chronic insomnia disorder. Three clinical practice algorithms are also included.
17Psychological Treatment of Comorbid Insomnia and Depression: A Double-Blind Randomized Placebo-Controlled Trial.PubMed
Kerstin Blom, Erik Forsell, Monica Hellberg, et al.
Psychother Psychosom. 2024;93(2):100-113. doi: 10.1159/000536063. Epub 2024 Jan 29.
INTRODUCTION: Insomnia and depression are highly prevalent disorders and commonly occur together. Cognitive behavioral therapy for insomnia, CBT-I, has been shown to be effective in treating insomnia and also comorbid depression. However, it is unclear whether effects of CBT-I on depression are specific or nonspecific. Also, depressive symptoms often remain too high after CBT-I, indicating a need for improved treatments. The objective was to determine whether combining CBT-I with CBT for depression, without increasing treatment length, reduces both insomnia and depression more than CBT for depression with a placebo insomnia intervention. METHODS: A 12-week double-blind randomized controlled trial with a 6-month follow-up in a psychiatric setting using therapist-guided internet-delivered treatments was conducted. Patients (N = 126) were diagnosed with insomnia disorder and major depression by physicians. Primary outcome measures were as follows: self-rating scales Insomnia Severity Index (ISI) and Montgomery-Åsberg Depression Rating Scale (MADRS-S). RESULTS: The combined treatment showed specific effects on insomnia severity over the control treatment (p = 0.007) but was not more effective in reducing depression severity. Within-group effects (Cohen's d) at post and at 6 months were as follows: ISI 1.40 and 1.42 (combined treatment), 0.95 and 1.00 (control); MADRS-S 0.97 and 1.12 (combined), 0.88 and 0.89 (control). CONCLUSIONS: CBT-I shows large specific effects on insomnia severity and is superior to control in this regard. Both treatments had similar effects on depression severity, i.e., combining CBT-I with CBT for depression did not enhance outcomes on depression compared to control. We suggest CBT-I should always be offered to patients with insomnia and depression comorbidity, possibly as the first-hand choice. Combining it with a psychological treatment for depression could be too burdening and may not be beneficial.
18Comorbid Insomnia and Sleep Apnea: Assessment and Management Approaches.PubMed
Alexander Sweetman, Leon Lack, Megan Crawford, et al.
Sleep Med Clin. 2022 Dec;17(4):597-617. doi: 10.1016/j.jsmc.2022.07.006. Epub 2022 Oct 9.
Comorbid insomnia and sleep apnea (COMISA) is a highly prevalent and debilitating condition that is more difficult to treat compared with insomnia alone or sleep apnea alone. Approximately 30% to 50% of sleep clinic patients with sleep apnea report comorbid insomnia symptoms. Comorbid insomnia is associated with lower adherence to positive airway pressure therapy for obstructive sleep apnea. Management approaches that include targeted treatments for both insomnia and sleep apnea lead to the best treatment outcomes for patients with COMISA. Therefore, sleep clinics should incorporate insomnia and COMISA management pathways including access to cognitive behavioral therapy for insomnia.
19Co-morbid insomnia and sleep apnea (COMISA): recent research and future directions.PubMed
Alexander Sweetman, Amal Osman, Leon Lack, et al.
Curr Opin Pulm Med. 2023 Nov 1;29(6):567-573. doi: 10.1097/MCP.0000000000001007. Epub 2023 Aug 29.
PURPOSE OF REVIEW: Insomnia and obstructive sleep apnea have previously been viewed as completely independent conditions. However, there is now increasing recognition that insomnia and sleep apnea frequently co-occur. Co-morbid insomnia and sleep apnea (COMISA) is a highly prevalent condition that is associated with impairment of sleep, daytime function, mental health and physical health outcomes, and mortality risk. This review aims to provide an update on COMISA prevalence, consequences, treatment approaches, and future research directions. RECENT FINDINGS: People with COMISA experience worse sleep, mental health, physical health, quality of life and longevity compared to people with neither condition, and often compared to those with insomnia alone and sleep apnea alone. Emerging evidence suggests that cognitive behavioral therapy for insomnia is an effective treatment in the presence of treated and untreated sleep apnea, that may also improve manifestations and subsequent management of sleep apnea. Future research is required to understand the etiology of COMISA, and to develop and implement tailored treatment approaches. SUMMARY: It is important for sleep and respiratory technicians, researchers and clinicians to be aware of the high co-morbidity rates, consequences, and treatment requirements of patients with co-morbid insomnia and sleep apnea.
20Association between age and comorbid insomnia and sleep apnea.PubMed
Meina Wu, Pei Xue, Jinzhu Yan, et al.
Sleep Med. 2024 Dec;124:659-661. doi: 10.1016/j.sleep.2024.11.011. Epub 2024 Nov 8.
PURPOSE: To investigate the age-related prevalence of comorbid insomnia and sleep apnea (COMISA). METHODS: A single-night polysomnography with video monitoring was conducted on 2176 Chinese adults (ages 18-102) to screen for obstructive sleep apnea (OSA). Insomnia was defined as difficulty initiating or maintaining sleep, or early morning awakening at least three times per week for more than three months, accompanied by daytime symptoms such as irritability, fatigue, or anxiety. RESULTS: Of the participants, 981 met the criteria for COMISA, defined by an apnea-hypopnea index (AHI) of ≥5 and the presence of insomnia. Compared to patients with OSA only (n = 433), COMISA patients were more often female (48 % vs. 24 %), had longer sleep onset latency (5.8 min), shorter total sleep time (14.0 min), lower AHI (14.4 points), and higher mean peripheral oxygen saturation (0.6 %; all p < 0.05). The prevalence of COMISA versus OSA only was 51.9 % vs. 48.1 % in participants under 50 years, compared to 78.1 % vs. 21.9 % in those aged 70 or older. Logistic regression analysis adjusted for sex showed a 3 % increase in the odds of COMISA (95 % CI: 1.02-1.04) with each additional year of age. CONCLUSIONS: Our findings reveal a significant association between increasing age and the development of COMISA, underscoring the need for heightened clinical awareness of this condition in elderly patients.
21The neurobiology, investigation, and treatment of chronic insomnia.PubMed
Dieter Riemann, Christoph Nissen, Laura Palagini, et al.
Lancet Neurol. 2015 May;14(5):547-58. doi: 10.1016/S1474-4422(15)00021-6. Epub 2015 Apr 12.
Chronic insomnia is defined by difficulties in falling asleep, maintaining sleep, and early morning awakening, and is coupled with daytime consequences such as fatigue, attention deficits, and mood instability. These symptoms persist over a period of at least 3 months (Diagnostic and Statistical Manual 5 criteria). Chronic insomnia can be a symptom of many medical, neurological, and mental disorders. As a disorder, it incurs substantial health-care and occupational costs, and poses substantial risks for the development of cardiovascular and mental disorders, including cognitive deficits. Family and twin studies confirm that chronic insomnia can have a genetic component (heritability coefficients between 42% and 57%), whereas the investigation of autonomous and central nervous system parameters has identified hyperarousal as a final common pathway of the pathophysiology, implicating an imbalance of sleep-wake regulation consisting of either overactivity of the arousal systems, hypoactivity of the sleep-inducing systems, or both. Insomnia treatments include benzodiazepines, benzodiazepine-receptor agonists, and cognitive behavioural therapy. Treatments currently under investigation include transcranial magnetic or electrical brain stimulation, and novel methods to deliver psychological interventions.
22The hyperarousal model of insomnia: a review of the concept and its evidence.PubMed
Dieter Riemann, Kai Spiegelhalder, Bernd Feige, et al.
Sleep Med Rev. 2010 Feb;14(1):19-31. doi: 10.1016/j.smrv.2009.04.002. Epub 2009 May 28.
Primary insomnia is defined as difficulties in falling asleep, maintaining sleep or non-restorative sleep accompanied by significantly impaired daytime functioning in the absence of a specific physical, mental or substance-related cause. The current review provides substantial support for the concept that hyperarousal processes from the molecular to the higher system level play a key role in the pathophysiology of primary insomnia. Autonomous, neuroendocrine, neuroimmunological, electrophysiological and neuroimaging studies demonstrate increased levels of arousal in primary insomnia during both night and daytime. In the light of neurobiological theories of sleep-wake regulation, primary insomnia may be conceptualized as a final common pathway resulting from the interplay between a genetic vulnerability for an imbalance between arousing and sleep-inducing brain activity, psychosocial/medical stressors and perpetuating mechanisms including dysfunctional sleep-related behavior, learned sleep preventing associations and other cognitive factors like tendency to worry/ruminate.
23Insomnia Neurobiology and Therapy.PubMed
Alexa Kane, Rachel Marie E Salas
Semin Neurol. 2025 May;45(3):401-409. doi: 10.1055/a-2624-5696. Epub 2025 Jun 26.
Insomnia is highly prevalent in clinical practice and can present independently or alongside other medical and mental health disorders. Insomnia is a risk factor for the development and exacerbation of medical and mental health conditions. Behavioral and pharmacological treatments for insomnia are available. In this article, we review important mechanisms associated with insomnia including the hyperarousal model of insomnia and the neurobiology of insomnia. We then review the treatment approaches and management strategies for insomnia including cognitive behavioral therapy for insomnia, transcranial magnetic stimulation, pharmacologic treatment, and adjunctive treatments for insomnia.
24BDNF in sleep, insomnia, and sleep deprivation.PubMed
Karen Schmitt, Edith Holsboer-Trachsler, Anne Eckert
Ann Med. 2016;48(1-2):42-51. doi: 10.3109/07853890.2015.1131327. Epub 2016 Jan 13.
The protein brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors involved in plasticity of neurons in several brain regions. There are numerous evidence that BDNF expression is decreased by experiencing psychological stress and that, accordingly, a lack of neurotrophic support causes major depression. Furthermore, disruption in sleep homeostatic processes results in higher stress vulnerability and is often associated with stress-related mental disorders. Recently, we reported, for the first time, a relationship between BDNF and insomnia and sleep deprivation (SD). Using a biphasic stress model as explanation approach, we discuss here the hypothesis that chronic stress might induce a deregulation of the hypothalamic-pituitary-adrenal system. In the long-term it leads to sleep disturbance and depression as well as decreased BDNF levels, whereas acute stress like SD can be used as therapeutic intervention in some insomniac or depressed patients as compensatory process to normalize BDNF levels. Indeed, partial SD (PSD) induced a fast increase in BDNF serum levels within hours after PSD which is similar to effects seen after ketamine infusion, another fast-acting antidepressant intervention, while traditional antidepressants are characterized by a major delay until treatment response as well as delayed BDNF level increase. Key messages Brain-derived neurotrophic factor (BDNF) plays a key role in the pathophysiology of stress-related mood disorders. The interplay of stress and sleep impacts on BDNF level. Partial sleep deprivation (PSD) shows a fast action on BDNF level increase.
25Bidirectional mechanism of comorbidity of depression and insomnia based on synaptic plasticity.PubMed
Fanhao Meng, Long Wang
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Oct 28;48(10):1518-1528. doi: 10.11817/j.issn.1672-7347.2023.230082.
Insomnia is one of the most common accompanying symptoms of depression, with both sharing highly overlapping molecular pathways. The same pathological changes can trigger comorbidity of insomnia and depression, which further forms a vicious cycle with the involvement of more mechanisms and disease progression. Thus, understanding the potential interaction mechanisms between insomnia and depression is critical for clinical diagnosis and treatment. Comorbidity genetic factors, the hypothalamic-pituitary-adrenal axis, along with circadian rhythms of cortisol and the brain reward mechanism, are important ways in contributing to the comorbidity occurrence and development. However, owing to lack of pertinent investigational data, intricate molecular mechanisms necessitate further elaboration. Synaptic plasticity is a solid foundation for neural homeostasis. Pathological alterations of depression and insomnia may perturb the production and release of neurotransmitter, dendritic spine remodeling and elimination, which converges and reflects in aberrant synaptic dynamics. Hence, the introduction of synaptic plasticity research route and the construction of a comprehensive model of depression and insomnia comorbidity can provide new ideas for clinical depression insomnia comorbidity treatment plans.
26Cannabinoids and Sleep/Wake Control.PubMed
Mónica Méndez-Díaz, Alejandra E Ruiz-Contreras, Jacqueline Cortés-Morelos, et al.
Adv Exp Med Biol. 2021;1297:83-95. doi: 10.1007/978-3-030-61663-2_6.
The sleep-wake cycle is a complex process that includes wake (W), non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep. Each phase is regulated by specialized brain structures that, by means of different neurotransmitters, maintain the constant expression of the sleep-wake cycle. Molecules like orexin, serotonin, noradrenaline, histamine, for waking; GABA, adenosine, prostaglandins, for NREM sleep and acetylcholine and glutamate for REM sleep, among other molecules are responsible for the expression and maintenance of each phase. When the endocannabinoid system was being described for the first time, almost three decades ago, oleamide's sleep promoting properties were highlighted. Nowadays, enough evidence has been cumulated to support the endocannabinoid system role in the sleep-wake cycle regulation. The endocannabinoids oleamide anandamide, and 2-arachidonylglycerol promote NREM and/or REM sleep via the CB1R, thereby making this system a target to treat sleep disorders, such as insomnia.
27Sleep Pharmacogenetics: Personalized Sleep-Wake Therapy.PubMed
Sebastian C Holst, Amandine Valomon, Hans-Peter Landolt
Annu Rev Pharmacol Toxicol. 2016;56:577-603. doi: 10.1146/annurev-pharmtox-010715-103801. Epub 2015 Nov 2.
Research spanning (genetically engineered) animal models, healthy volunteers, and sleep-disordered patients has identified the neurotransmitters and neuromodulators dopamine, serotonin, norepinephrine, histamine, hypocretin, melatonin, glutamate, acetylcholine, γ-amino-butyric acid, and adenosine as important players in the regulation and maintenance of sleep-wake-dependent changes in neuronal activity and the sleep-wake continuum. Dysregulation of these neurochemical systems leads to sleep-wake disorders. Most currently available pharmacological treatments are symptomatic rather than causal, and their beneficial and adverse effects are often variable and in part genetically determined. To evaluate opportunities for evidence-based personalized medicine with present and future sleep-wake therapeutics, we review here the impact of known genetic variants affecting exposure of and sensitivity to drugs targeting the neurochemistry of sleep-wake regulation and the pathophysiology of sleep-wake disturbances. Many functional polymorphisms modify drug response phenotypes relevant for sleep. To corroborate the importance of these and newly identified variants for personalized sleep-wake therapy, human sleep pharmacogenetics should be complemented with pharmacogenomic investigations, research about sleep-wake-dependent pharmacological actions, and studies in mice lacking specific genes. These strategies, together with future knowledge about epigenetic mechanisms affecting sleep-wake physiology and treatment outcomes, may lead to potent and safe novel therapies for the increasing number of sleep-disordered patients (e.g., in aged populations).
28Clinical and Experimental Human Sleep-Wake Pharmacogenetics.PubMed
Hans-Peter Landolt, Sebastian C Holst, Amandine Valomon
Handb Exp Pharmacol. 2019;253:207-241. doi: 10.1007/164_2018_175.
Sleep and wakefulness are highly complex processes that are elegantly orchestrated by fine-tuned neurochemical changes among neuronal and non-neuronal ensembles, nuclei, and networks of the brain. Important neurotransmitters and neuromodulators regulating the circadian and homeostatic facets of sleep-wake physiology include melatonin, γ-aminobutyric acid, hypocretin, histamine, norepinephrine, serotonin, dopamine, and adenosine. Dysregulation of these neurochemical systems may cause sleep-wake disorders, which are commonly classified into insomnia disorder, parasomnias, circadian rhythm sleep-wake disorders, central disorders of hypersomnolence, sleep-related movement disorders, and sleep-related breathing disorders. Sleep-wake disorders can have far-reaching consequences on physical, mental, and social well-being and health and, thus, need be treated with effective and rational therapies. Apart from behavioral (e.g., cognitive behavioral therapy for insomnia), physiological (e.g., chronotherapy with bright light), and mechanical (e.g., continuous positive airway pressure treatment of obstructive sleep apnea) interventions, pharmacological treatments often are the first-line clinical option to improve disturbed sleep and wake states. Nevertheless, not all patients respond to pharmacotherapy in uniform and beneficial fashion, partly due to genetic differences. The improved understanding of the neurochemical mechanisms regulating sleep and wakefulness and the mode of action of sleep-wake therapeutics has provided a conceptual framework, to search for functional genetic variants modifying individual drug response phenotypes. This article will summarize the currently known genetic polymorphisms that modulate drug sensitivity and exposure, to partly determine individual responses to sleep-wake pharmacotherapy. In addition, a pharmacogenetic strategy will be outlined how based upon classical and opto-/chemogenetic strategies in animals, as well as human genetic associations, circuit mechanisms regulating sleep-wake functions in humans can be identified. As such, experimental human sleep-wake pharmacogenetics forms a bridge spanning basic research and clinical medicine and constitutes an essential step for the search and development of novel sleep-wake targets and therapeutics.
29[Hypocretins and adenosine in the regulation of sleep].PubMed
R J Salín-Pascual
Rev Neurol. 2004;39(4):354-8.
OBJECTIVES: To review the recent discovery of hypocretins (orexins) and their link to the pathophysiology of narcolepsy and the role of adenosine in the integration of brain metabolism and sleep. DEVELOPMENT: The importance of the functions carried out by the hypothalamus in the regulation of sleep and the waking state has been consolidated by the discovery of hypocretins and the role played by cerebral adenosine. Hypocretins are two peptides made up of 33 and 28 amino acids whose neurons are located predominantly in the lateral hypothalamus and surrounding regions. In the Doberman canine narcolepsy model, in which this disease is presented with an autosomal recessive pattern, a mutation was detected in one of the receptors involved in the hypocretin system, namely the hypocretin-2 receptor. Failures in the hypocretin system have been confirmed as a key factor in narcolepsy by other findings in laboratory animals and humans. Adenosine, on the other hand, is accumulated during the waking state as a result of neuronal metabolism and this in turn is related to drowsiness. Sleep episodes lower the levels of this substance in the brain. Adenosine receptor antagonists increase wakefulness (e.g. caffeine), while the agonists promote slow-wave sleep. CONCLUSIONS: Hypocretins and adenosine from the hypothalamus perform functions involving the regulation of sleep and wakefulness. Understanding these two systems can have repercussions on clinical problems such as insomnia, hypersomnia and other neuropsychiatric disorders.
30Sleep, insomnia and mental health.PubMed
Laura Palagini, Elisabeth Hertenstein, Dieter Riemann, et al.
J Sleep Res. 2022 Aug;31(4):e13628. doi: 10.1111/jsr.13628. Epub 2022 May 4.
While sleep serves important regulatory functions for mental health, sleep disturbances, in particular insomnia, may favour a state of allostatic overload impairing brain neuroplasticity and stress immune pathways, hence contributing to mental disorders. In this framework, the aim of this work was to link current understanding about insomnia mechanisms with current knowledge about mental health dysregulatory mechanisms. The focus of the present work was on mood, anxiety, and psychotic disorders, which represent important challenges in clinical practice. Literature searches were conducted on clinical, neurobiological, and therapeutic implications for insomnia comorbid with these mental disorders. Given the complexity and heterogeneity of the existing literature, we ended up with a narrative review. Insomnia may play an important role as a risk factor, a comorbid condition and transdiagnostic symptom for many mental disorders including mood/anxiety disorders and schizophrenia. Insomnia may also play a role as a marker of disrupted neuroplasticity contributing to dysregulation of different neurobiological mechanisms involved in these different mental conditions. In this framework, insomnia treatment may not only foster normal sleep processes but also the stress system, neuroinflammation and brain plasticity. Insomnia treatment may play an important preventive and neuroprotective role with cognitive behavioural therapy for insomnia being the treatment with important new evidence of efficacy for insomnia, psychopathology, and indices of disrupted neuroplasticity. On the other hand, pharmacological pathways for insomnia treatment in these mental conditions are still not well defined. Therapeutic options acting on melatonergic systems and new therapeutic options acting on orexinergic systems may represents interesting pathways of interventions that may open new windows on insomnia treatment in mental disorders.
31Insomnia and depression.PubMed
Ruth M Benca, Michael J Peterson
Sleep Med. 2008 Sep;9 Suppl 1:S3-9. doi: 10.1016/S1389-9457(08)70010-8.
It is clear that insomnia and depression are intimately related, which may suggest an overlapping neurobiology. Although much progress has been made toward understanding how these disorders relate to each other, the exact neurobiological mechanisms that link them remain elusive. Sleep changes in depression may be associated with abnormal neurotransmission, genetic polymorphisms, HPA overactivity, impaired plasticity, or most likely a combination of factors. It is therefore crucial that sleep assessments go beyond traditional polysomnography to include a more expanded set of objective measures in the hope that these will uncover the common neurobiology that is thought to underlie insomnia and depression.
32Depression in sleep disturbance: A review on a bidirectional relationship, mechanisms and treatment.PubMed
Hong Fang, Sheng Tu, Jifang Sheng, et al.
J Cell Mol Med. 2019 Apr;23(4):2324-2332. doi: 10.1111/jcmm.14170. Epub 2019 Feb 7.
Sleep disturbance is the most prominent symptom in depressive patients and was formerly regarded as a main secondary manifestation of depression. However, many longitudinal studies have identified insomnia as an independent risk factor for the development of emerging or recurrent depression among young, middle-aged and older adults. This bidirectional association between sleep disturbance and depression has created a new perspective that sleep problems are no longer an epiphenomenon of depression but a predictive prodromal symptom. In this review, we highlight the treatment of sleep disturbance before, during and after depression, which probably plays an important role in improving outcomes and preventing the recurrence of depression. In clinical practice, pharmacological therapies, including hypnotics and antidepressants, and non-pharmacological therapies are typically applied. A better understanding of the pathophysiological mechanisms between sleep disturbance and depression can help psychiatrists better manage this comorbidity.
33Depression and lifestyle: Focusing on nutrition, exercise, and their possible relevance to molecular mechanisms.PubMed
Hiroshi Kunugi
Psychiatry Clin Neurosci. 2023 Aug;77(8):420-433. doi: 10.1111/pcn.13551. Epub 2023 Apr 25.
Accumulating evidence has suggested the important role of lifestyle factors in depressive disorder. This paper aimed to introduce and outline recent research on epidemiological and intervention studies on lifestyle-related factors in depressive disorder with a special focus on diet. Evidence on exercise, sleep. and related behaviors is also described. Here, findings from meta-analytic studies are emphasized and related studies by the author's research group are introduced. Dietary factors that increase the risk of the illness include energy overload, skipping breakfast, unhealthy diet styles such as Western diet, inflammation-prone diet, and high consumption of ultraprocessed food (UPF). Nutritional imbalances such as inadequate intake of protein, fish (Ω3 polyunsaturated fatty acids), vitamins (folate and vitamin D), and minerals (iron and zinc) increases the risk of depression. Poor oral hygiene, food allergy, addiction to alcohol, and smoking constitute risk factors. Sedentary lifestyle and increased screen time (e.g. video games and the internet) confer the risk of depression. Insomnia and disturbed sleep-wake rhythm are also involved in the pathogenesis of depression. There is accumulating evidence at the meta-analysis level for interventions to modify these lifestyle habits in the protection and treatment of depressive disorder. Main biological mechanisms of the link between lifestyle factors and depression include monoamine imbalance, inflammation, altered stress response, oxidative stress, and dysfunction of brain-derived neurotrophic factor, although other players such as insulin, leptin, and orexin also play a role. To increase resilience to modern stress and ameliorate depression through modification of lifestyle habits, a list of 30 recommendable interventions is presented.
34Insomnia and Risk of Cardiovascular Disease.PubMed
Sogol Javaheri, Susan Redline
Chest. 2017 Aug;152(2):435-444. doi: 10.1016/j.chest.2017.01.026. Epub 2017 Jan 30.
Insomnia is the most prevalent sleep disorder in the United States and has high comorbidity with a number of cardiovascular diseases (CVDs). In the past decade, a number of observational studies have demonstrated an association between insomnia and incident cardiovascular disease (CVD) morbidity and mortality, including hypertension (HTN), coronary heart disease (CHD), and heart failure (HF). Despite some inconsistencies in the literature, likely due to variations in how insomnia is defined and measured, the existing data suggest that insomnia, especially when accompanied by short sleep duration, is associated with increased risk for HTN, CHD and recurrent acute coronary syndrome, and HF. Purported mechanisms likely relate to dysregulation of the hypothalamic-pituitary axis, increased sympathetic nervous system activity, and increased inflammation. This paper reviews the most recent studies of insomnia and CVD and the potential pathophysiological mechanisms underlying this relationship and highlights the need for randomized trials to further elucidate the nature of the relationship between insomnia and CVD.
35The gut microbiota-bile acid axis links the positive association between chronic insomnia and cardiometabolic diseases.PubMed
Zengliang Jiang, Lai-Bao Zhuo, Yan He, et al.
Nat Commun. 2022 May 30;13(1):3002. doi: 10.1038/s41467-022-30712-x.
Evidence from human cohorts indicates that chronic insomnia is associated with higher risk of cardiometabolic diseases (CMD), yet whether gut microbiota plays a role is unclear. Here, in a longitudinal cohort (n = 1809), we find that the gut microbiota-bile acid axis may link the positive association between chronic insomnia and CMD. Ruminococcaceae UCG-002 and Ruminococcaceae UCG-003 are the main genera mediating the positive association between chronic insomnia and CMD. These results are also observed in an independent cross-sectional cohort (n = 6122). The inverse associations between those gut microbial biomarkers and CMD are mediated by certain bile acids (isolithocholic acid, muro cholic acid and nor cholic acid). Habitual tea consumption is prospectively associated with the identified gut microbiota and bile acids in an opposite direction compared with chronic insomnia. Our work suggests that microbiota-bile acid axis may be a potential intervention target for reducing the impact of chronic insomnia on cardiometabolic health.
36Obesity and sleep disorders: A bidirectional relationship.PubMed
Michela Figorilli, Fernanda Velluzzi, Stefania Redolfi
Nutr Metab Cardiovasc Dis. 2025 Jun;35(6):104014. doi: 10.1016/j.numecd.2025.104014. Epub 2025 Mar 15.
AIMS: Obesity and sleep disorders are highly prevalent conditions with profound implications for public health. Emerging evidence highlights a bidirectional relationship between these two conditions, with each exacerbating the other in a complex interplay of behavioral, physiological, and hormonal mechanisms. Sleep deprivation and poor sleep quality contribute to energy imbalance through dysregulation of appetite hormones (e.g., leptin and ghrelin), increased caloric intake, and reduced physical activity. Conversely, sleep disorders such as obstructive sleep apnea syndrome (OSAS), insomnia, and restless leg syndrome (RLS) are significantly more common in individuals with obesity. DATA SYNTHESIS: This review explores the pathophysiological mechanisms underlying this relationship, including the roles of inflammation, autonomic dysregulation, and neuroendocrine pathways. Sleep loss exacerbates metabolic syndrome components, including insulin resistance and dyslipidemia, further perpetuating weight gain. Similarly, obesity-induced sleep disorders lead to pro-inflammatory states, vascular dysfunction, and sympathetic overactivation, compounding cardiometabolic risks. Specific conditions like OSA and RLS are examined as models of this interdependence, emphasizing their shared pathways and clinical implications. CONCLUSIONS: The bidirectional link between obesity and sleep disorders underscores the importance of integrating sleep assessment and management into obesity treatment strategies. Addressing this relationship could mitigate the progression of cardiometabolic comorbidities and improve overall health outcomes. Moreover, the intertwined dynamics between obesity, sleep disorders, and mental health-mediated by inflammatory pathways, hormonal dysregulation, and neurobehavioral factors-highlight the critical need for integrated treatment approaches targeting physical, psychological, and sleep-related dimensions to enhance health and quality of life.
37Sleep Characteristics and Risk of Stroke and Dementia: An Observational and Mendelian Randomization Study.PubMed
Chutian Guo, Eric L Harshfield, Hugh S Markus
Neurology. 2024 Mar 12;102(5):e209141. doi: 10.1212/WNL.0000000000209141. Epub 2024 Feb 13.
BACKGROUND AND OBJECTIVES: Sleep disturbances are implicated as risk factors of both stroke and dementia. However, whether these associations are causal and whether treatment of sleep disorders could reduce stroke and dementia risk remain uncertain. We aimed to evaluate associations and ascertain causal relationships between sleep characteristics and stroke/dementia risk and MRI markers of small vessel disease (SVD). METHODS: We used data sets from a multicenter population-based study and summary statistics from genome-wide association studies (GWASs) of sleep characteristics and outcomes. We analyzed 502,383 UK Biobank participants with self-reported sleep measurements, including sleep duration, insomnia, chronotype, napping, daytime dozing, and snoring. In observational analyses, the primary outcomes were incident stroke, dementia, and their subtypes, alongside SVD markers. Hazard ratios (HRs) and odds ratios (ORs) were adjusted for age, sex, and ethnicity, and additional vascular risk factors. In Mendelian randomization (MR) analyses, ORs or risk ratios are reported for the association of each genetic score with clinical or MRI end points. RESULTS: Among 502,383 participants (mean [SD] age, 56.5 [8.1] years; 54.4% female), there were 7,668 cases of all-cause dementia and 10,334 strokes. In longitudinal analyses, after controlling for cardiovascular risk factors, participants with insomnia, daytime napping, and dozing were associated with increased risk of any stroke (HR 1.05, 95% CI 1.01-1.11, = 8.53 × 10; HR 1.09, 95% CI 1.05-1.14, = 3.20 × 10; HR 1.19, 95% CI 1.08-1.32, = 4.89 × 10, respectively). Almost all sleep measures were associated with dementia risk (all < 0.001, except insomnia). Cross-sectional analyses identified associations between napping, snoring, and MRI markers of SVD (all < 0.001). MR analyses supported a causal link between genetically predicted insomnia and increased stroke risk (OR 1.31, 95% CI 1.13-1.51, = 0.00072), but not with dementia or SVD markers. DISCUSSION: We found that multiple sleep measures predicted future risk of stroke and dementia, but these associations were attenuated after controlling for cardiovascular risk factors and were absent in MR analyses for Alzheimer disease. This suggests possible confounding or reverse causation, implying caution before proposing sleep disorder modifications for dementia treatment.
38Preclinical models of insomnia: advances, limitations, and future directions for drug discovery.PubMed
Oscar Arias-Carrión
Expert Opin Drug Discov. 2025 Aug;20(8):1061-1074. doi: 10.1080/17460441.2025.2528135. Epub 2025 Jul 2.
INTRODUCTION: Insomnia is a highly prevalent and clinically burdensome disorder that profoundly affects cognition, emotional regulation, cardiometabolic health, and neurodegenerative progression. Despite advances in understanding its neurobiology, current animal models fail to capture the chronic, heterogeneous, and comorbid nature of human insomnia, impeding progress in translational drug discovery. AREAS COVERED: This narrative review critically appraises genetic, environmental, pharmacological, and circuit-level models of insomnia, focusing on their translational relevance to drug discovery and is based on literature searches using PubMed and Scopus (2000-2025) where key systematic reviews were identified. The author also discusses how oversimplified paradigms and limited modeling of comorbidity constrain clinical applicability and highlight emerging tools - optogenetics, chemogenetics, CRISPR, wearable EEG, and AI - that enable high-resolution mapping of sleep - wake mechanisms. EXPERT OPINION: A paradigm shift toward integrated, multidimensional models is urgently needed to reflect the complexity of chronic insomnia better. Embedding these models into translational pipelines - through precision genetics, circuit manipulation, and AI-enhanced analytics - will accelerate mechanism-based drug discovery and support the development of durable, personalized treatments for this disabling and multifactorial disorder.
39European guideline for the diagnosis and treatment of insomnia.PubMed
Dieter Riemann, Chiara Baglioni, Claudio Bassetti, et al.
J Sleep Res. 2017 Dec;26(6):675-700. doi: 10.1111/jsr.12594. Epub 2017 Sep 5.
This European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia. The guideline is based on a systematic review of relevant meta-analyses published till June 2016. The target audience for this guideline includes all clinicians involved in the management of insomnia, and the target patient population includes adults with chronic insomnia disorder. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the evidence and guide recommendations. The diagnostic procedure for insomnia, and its co-morbidities, should include a clinical interview consisting of a sleep history (sleep habits, sleep environment, work schedules, circadian factors), the use of sleep questionnaires and sleep diaries, questions about somatic and mental health, a physical examination and additional measures if indicated (i.e. blood tests, electrocardiogram, electroencephalogram; strong recommendation, moderate- to high-quality evidence). Polysomnography can be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders), in treatment-resistant insomnia, for professional at-risk populations and when substantial sleep state misperception is suspected (strong recommendation, high-quality evidence). Cognitive behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (strong recommendation, high-quality evidence). A pharmacological intervention can be offered if cognitive behavioural therapy for insomnia is not sufficiently effective or not available. Benzodiazepines, benzodiazepine receptor agonists and some antidepressants are effective in the short-term treatment of insomnia (≤4 weeks; weak recommendation, moderate-quality evidence). Antihistamines, antipsychotics, melatonin and phytotherapeutics are not recommended for insomnia treatment (strong to weak recommendations, low- to very-low-quality evidence). Light therapy and exercise need to be further evaluated to judge their usefulness in the treatment of insomnia (weak recommendation, low-quality evidence). Complementary and alternative treatments (e.g. homeopathy, acupuncture) are not recommended for insomnia treatment (weak recommendation, very-low-quality evidence).
40The Insomnia Severity Index: psychometric indicators to detect insomnia cases and evaluate treatment response.PubMed
Charles M Morin, Geneviève Belleville, Lynda Bélanger, et al.
Sleep. 2011 May 1;34(5):601-8. doi: 10.1093/sleep/34.5.601.
BACKGROUND: Although insomnia is a prevalent complaint with significant morbidity, it often remains unrecognized and untreated. Brief and valid instruments are needed both for screening and outcome assessment. This study examined psychometric indices of the Insomnia Severity Index (ISI) to detect cases of insomnia in a population-based sample and to evaluate treatment response in a clinical sample. METHODS: Participants were 959 individuals selected from the community for an epidemiological study of insomnia (Community sample) and 183 individuals evaluated for insomnia treatment and 62 controls without insomnia (Clinical sample). They completed the ISI and several measures of sleep quality, fatigue, psychological symptoms, and quality of life; those in the Clinical sample also completed sleep diaries, polysomnography, and interviews to validate their insomnia/good sleep status and assess treatment response. In addition to standard psychometric indices of reliability and validity, item response theory analyses were computed to examine ISI item response patterns. Receiver operating curves were used to derive optimal cutoff scores for case identification and to quantify the minimally important changes in relation to global improvement ratings obtained by an independent assessor. RESULTS: ISI internal consistency was excellent for both samples (Cronbach α of 0.90 and 0.91). Item response analyses revealed adequate discriminatory capacity for 5 of the 7 items. Convergent validity was supported by significant correlations between total ISI score and measures of fatigue, quality of life, anxiety, and depression. A cutoff score of 10 was optimal (86.1% sensitivity and 87.7% specificity) for detecting insomnia cases in the community sample. In the clinical sample, a change score of -8.4 points (95% CI: -7.1, -9.4) was associated with moderate improvement as rated by an independent assessor after treatment. CONCLUSION: These findings provide further evidence that the ISI is a reliable and valid instrument to detect cases of insomnia in the population and is sensitive to treatment response in clinical patients.
41Test-retest reliability and validity of the Pittsburgh Sleep Quality Index in primary insomnia.PubMed
Jutta Backhaus, Klaus Junghanns, Andreas Broocks, et al.
J Psychosom Res. 2002 Sep;53(3):737-40. doi: 10.1016/s0022-3999(02)00330-6.
OBJECTIVE: Psychometric evaluation of the Pittsburgh Sleep Quality Index (PSQI) for primary insomnia. METHODS: The study sample consisted of 80 patients with primary insomnia (DSM-IV). The length of the test-retest interval was either 2 days or several weeks. Validity analyses were calculated for PSQI data and data from sleep diaries, as well as polysomnography. To evaluate the specificity of the PSQI, insomnia patients were compared with a control group of 45 healthy subjects. RESULTS: In primary insomnia patients, the overall PSQI global score correlation coefficient for test-retest reliability was .87. Validity analyses showed high correlations between PSQI and sleep log data and lower correlations with polysomnography data. A PSQI global score > 5 resulted in a sensitivity of 98.7 and specificity of 84.4 as a marker for sleep disturbances in insomnia patients versus controls. CONCLUSION: The PSQI has a high test-retest reliability and a good validity for patients with primary insomnia.
42[Insomnia].PubMed
Elisabeth Hertenstein, Carlotta Schneider, Christoph Nissen
Dtsch Med Wochenschr. 2023 Oct;148(21):1384-1390. doi: 10.1055/a-2182-0463. Epub 2023 Oct 11.
Patients with insomnia suffer from problems falling asleep and/or maintaining sleep. This has a negative effect on their daytime wellbeing and performance. Insomnia is primarily diagnosed by a detailed clinical history, supplemented by questionnaires and sleep diaries. Polysomnography may be necessary for the differential diagnosis of organic sleep disorders. Insomnia is a frequent comorbidity of most mental disorders and many physical diseases. It is treated according to guidelines with cognitive behavioural therapy for insomnia (CBT-I). CBT-I is offered in individual or group format as well as online-supported treatment. If behavioural therapy is not effective or not available, pharmacotherapy can be discussed.
43Effects of Tai Chi or Exercise on Sleep in Older Adults With Insomnia: A Randomized Clinical Trial.PubMed
Parco M Siu, Angus P Yu, Bjorn T Tam, et al.
JAMA Netw Open. 2021 Feb 1;4(2):e2037199. doi: 10.1001/jamanetworkopen.2020.37199.
IMPORTANCE: Previous studies that have shown tai chi to improve sleep were mainly based on subjective assessments, which might have produced results confounded by self-reporting bias. OBJECTIVE: To compare the effectiveness of tai chi for improving sleep in older adults with insomnia with conventional exercise and a passive control group using actigraphy-based objective measurements. DESIGN, SETTING, AND PARTICIPANTS: This randomized, 3-arm, parallel group, assessor-masked clinical trial was conducted at a single research unit in Hong Kong between August 2014 and August 2018. Eligible participants, aged 60 years or older and with chronic insomnia, were randomly allocated into tai chi training, exercise, and control groups. INTERVENTIONS: 12-week tai chi training, 12-week conventional exercise, and no intervention control. MAIN OUTCOMES AND MEASURES: Primary outcomes were measures taken from actigraphy sleep assessment. Secondary outcomes included remission of insomnia, insomnia treatment response, Pittsburgh Sleep Quality Index score, Insomnia Severity Index score, and self-reported sleep using a 7-day sleep diary. Assessments were performed at baseline, end of the intervention (postintervention), and 24 months after the intervention (follow-up). Data analysis was performed from September 2018 to August 2020. RESULTS: A total of 320 participants (mean [SD] age, 67.3 [6.8] years; mean [SD] insomnia duration, 124.4 [134.5] months; 256 [80.0%] women) were randomly allocated into control (110 participants), exercise (105 participants), and tai chi (105 participants) groups and included in the data analysis. Compared with the control group, the exercise and tai chi groups showed improved sleep efficiency (exercise vs control: adjusted mean difference, +3.5%; 95% CI, 1.8-5.2; P < .001; tai chi vs control: adjusted mean difference, +3.4%; 95% CI, 1.6-5.1; P < .001) and reductions of wake time after sleep onset (exercise vs control: -17.0 minutes; 95% CI, -24.9 to -9.0; P < .001; tai chi vs control: -13.3 minutes; 95% CI, -21.3 to -5.2; P = .001) and number of awakenings (exercise vs control: -2.8 times; 95% CI, -4.0 to -1.6; P < .001; tai chi vs control: -2.2 times; 95% CI, -3.5 to -1.0; P < .001) as assessed by actigraphy at postintervention; although there were no significant differences between the exercise and tai chi groups. The actigraphy-assessed beneficial effects were maintained in both intervention groups at follow-up. CONCLUSIONS AND RELEVANCE: Conventional exercise and tai chi improved sleep and the beneficial effects sustained for 24 months, although the absolute improvements in sleep parameters were modest. Improvements in objective sleep parameters were not different between the tai chi and exercise groups, suggesting that tai chi can be an alternative approach for managing insomnia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02260843.
44Sleep, circadian rhythm, and physical activity patterns in depressive and anxiety disorders: A 2-week ambulatory assessment study.PubMed
Sonia Difrancesco, Femke Lamers, Harriëtte Riese, et al.
Depress Anxiety. 2019 Oct;36(10):975-986. doi: 10.1002/da.22949. Epub 2019 Jul 26.
BACKGROUND: Actigraphy may provide a more valid assessment of sleep, circadian rhythm (CR), and physical activity (PA) than self-reported questionnaires, but has not been used widely to study the association with depression/anxiety and their clinical characteristics. METHODS: Fourteen-day actigraphy data of 359 participants with current (n = 93), remitted (n = 176), or no (n = 90) composite international diagnostic interview depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Objective estimates included sleep duration (SD), sleep efficiency, relative amplitude (RA) between day-time and night-time activity, mid sleep on free days (MSF), gross motor activity (GMA), and moderate-to-vigorous PA (MVPA). Self-reported measures included insomnia rating scale, SD, MSF, metabolic equivalent total, and MVPA. RESULTS: Compared to controls, individuals with current depression/anxiety had a significantly different objective, but not self-reported, PA and CR: lower GMA (23.83 vs. 27.4 milli-gravity/day, p = .022), lower MVPA (35.32 vs. 47.64 min/day, p = .023), lower RA (0.82 vs. 0.83, p = .033). In contrast, self-reported, but not objective, sleep differed between people with current depression/anxiety compared to those without current disorders; people with current depression/anxiety reported both shorter and longer SD and more insomnia. More depressive/anxiety symptoms and number of depressive/anxiety diagnoses were associated with larger disturbances of the actigraphy measures. CONCLUSION: Actigraphy provides ecologically valid information on sleep, CR, and PA that enhances data from self-reported questionnaires. As those with more severe or comorbid forms showed the lowest PA and most CR disruptions, the potential for adjunctive behavioral and chronotherapy interventions should be explored, as well as the potential of actigraphy to monitor treatment response to such interventions.
45Digital Cognitive Behavioral Therapy for Insomnia Using a Smartphone Application in China: A Pilot Randomized Clinical Trial.PubMed
Cheng Zhang, Yuxuan Liu, Xiaoming Guo, et al.
JAMA Netw Open. 2023 Mar 1;6(3):e234866. doi: 10.1001/jamanetworkopen.2023.4866.
IMPORTANCE: Digital cognitive behavioral therapy for insomnia (DCBT-I) requires adaptation to different sociocultural contexts. Moreover, studies comparing DCBT-I and sleep education in the same operating interface are lacking. OBJECTIVE: To investigate the efficacy of a smartphone-based Chinese culture-adapted DCBT-I application (app) for insomnia compared with sleep education using the same app. DESIGN, SETTING, AND PARTICIPANTS: This was a single-blinded, randomized clinical trial conducted from March 2021 to January 2022. Screening and randomization were conducted at Peking University First Hospital. Follow-up visits were performed online or in the same hospital. After assessing for eligibility, eligible participants were enrolled and allocated (1:1) to DCBT-I or sleep education groups. Data were analyzed from January to February 2022. INTERVENTIONS: A Chinese smartphone-based app with the same interface was used in both DCBT-I and sleep education groups over 6 weeks, with 1-, 3-, and 6-month follow-ups. MAIN OUTCOMES AND MEASURES: The primary outcome was Insomnia Severity Index (ISI) scores with the intention-to-treat principle. Secondary and exploratory outcomes included sleep diary measures; self-reported scales assessing dysfunctional beliefs about sleep, mental health, and quality of life; and smart bracelet measures. RESULTS: Of 82 participants (mean [SD] age, 49.67 [14.49] years; 61 [74.4%] females), with 41 randomized to sleep education and 41 randomized to DCBT-I; 77 participants completed the 6-week intervention (39 participants in the sleep education group and 38 participants in the DCBT-I group; full analysis data set) and 73 completed the 6-month follow-up (per protocol data set). Mean (SD) ISI scores in the DCBT-I group were significantly lower than those in the sleep education group after the 6-week intervention (12.7 [4.8] points vs 14.9 [5.0] points; Cohen d = 0.458; P = .048) and at the 3-month follow-up (12.1 [5.4] points vs 14.8 [5.5] points; Cohen d = 0.489; P = .04). There were significant improvements from before to after the intervention for both the sleep education and DCBT-I groups, with large effect sizes(sleep education: d = 1.13; DCBT-I: d = 1.71). Some of the sleep diary measures and self-reported scales showed more improvements in the DCBT-I group than sleep education group, such as total sleep time (mean [SD]: 3 months, 403.9 [57.6] minutes vs 363.2 [72.3] minutes; 6 months, 420.3 [58.0] minutes vs 389.7 [59.4] minutes) and sleep efficiency (mean [SD]: 3 months, 87.4% [8.3%] vs 76.7% [12.1%]; 6 months, 87.5% [8.2%] vs 78.1% [10.9%]). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the smartphone-based Chinese culture-adapted DCBT-I improved insomnia severity compared with sleep education. Future multicenter clinical trials with large sample sizes are needed to validate its effectiveness in the Chinese population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04779372.
46Bi-directional relationships between co-morbid insomnia and sleep apnea (COMISA).PubMed
Alexander Sweetman, Leon Lack, R Doug McEvoy, et al.
Sleep Med Rev. 2021 Dec;60:101519. doi: 10.1016/j.smrv.2021.101519. Epub 2021 Jun 23.
Insomnia and obstructive sleep apnea (OSA) commonly co-occur. Approximately 30-50% of patients with OSA report clinically significant insomnia symptoms, and 30-40% of patients with chronic insomnia fulfil diagnostic criteria for OSA. Compared to either insomnia or OSA alone, co-morbid insomnia and sleep apnea (COMISA) is associated with greater morbidity for patients, complex diagnostic decisions for clinicians, and reduced response to otherwise effective treatment approaches. Potential bi-directional causal relationships between the mechanisms and manifestations of insomnia and OSA could play an integral role in the development and management of COMISA. A greater understanding of these relationships is required to guide personalized diagnostic and treatment approaches for COMISA. This review summarizes the available evidence of bi-directional relationships between COMISA, including epidemiological research, case studies, single-arm treatment studies, randomized controlled treatment trials, and objective sleep study data. This evidence is integrated into a conceptual model of COMISA to help refine the understanding of potential bi-directional causal relationships between the two disorders. This theoretical framework is essential to help guide future research, improve diagnostic tools, determine novel therapeutic targets, and guide tailored sequenced and multi-faceted treatment approaches for this common, complex, and debilitating condition.
47Sleep Disorders.PubMed
Milena K Pavlova, Véronique Latreille
Am J Med. 2019 Mar;132(3):292-299. doi: 10.1016/j.amjmed.2018.09.021. Epub 2018 Oct 4.
Sleep disorders are frequent and can have serious consequences on patients' health and quality of life. While some sleep disorders are more challenging to treat, most can be easily managed with adequate interventions. We review the main diagnostic features of 6 major sleep disorders (insomnia, circadian rhythm disorders, sleep-disordered breathing, hypersomnia/narcolepsy, parasomnias, and restless legs syndrome/periodic limb movement disorder) to aid medical practitioners in screening and treating sleep disorders as part of clinical practice.
48Sex differences in obstructive sleep apnoea.PubMed
Maria R Bonsignore, Tarja Saaresranta, Renata L Riha
Eur Respir Rev. 2019 Nov 6;28(154). doi: 10.1183/16000617.0030-2019. Print 2019 Dec 31.
Obstructive sleep apnoea (OSA) and obstructive sleep apnoea/hypopnoea syndrome (OSAHS) have long been considered predominantly male-related conditions. The clinical presentation of sleep disordered breathing in females differs from males and can vary with age and physiological status, menopause and pregnancy. Overall, females appear to be more symptomatic, with lower apnoea-hypopnoea index scores compared to males. Furthermore, they appear to have more prolonged partial upper airway obstruction, and may report insomnia as a symptom of OSAHS more frequently. As a consequence of these differences in clinical presentation, females with sleep disordered breathing are often underdiagnosed and undertreated compared to males. This review is aimed at discussing the epidemiology, clinical presentation, pathophysiology and hormonal and metabolic differences in females who present with OSA/OSAHS in comparison to males.
49Comorbid insomnia and sleep apnoea is associated with all-cause mortality.PubMed
Bastien Lechat, Sarah Appleton, Yohannes Adama Melaku, et al.
Eur Respir J. 2022 Jul 13;60(1). doi: 10.1183/13993003.01958-2021. Print 2022 Jul.
BACKGROUND: Increased mortality has been reported in people with insomnia and in those with obstructive sleep apnoea (OSA). However, these conditions commonly co-occur and the combined effect of comorbid insomnia and sleep apnoea (COMISA) on mortality risk is unknown. This study used Sleep Heart Health Study (SHHS) data to assess associations between COMISA and all-cause mortality risk. METHODS: Insomnia was defined as difficulties falling asleep, maintaining sleep and/or early morning awakenings from sleep ≥16 times per month, and daytime impairments. OSA was defined as an apnoea-hypopnoea index ≥15 events·h. COMISA was defined if both conditions were present. Multivariable adjusted Cox proportional hazards models were used to determine the association between COMISA and all-cause mortality (n=1210) over 15 years of follow-up. RESULTS: 5236 participants were included. 2708 (52%) did not have insomnia/OSA (reference group), 170 (3%) had insomnia-alone, 2221 (42%) had OSA-alone and 137 (3%) had COMISA. COMISA participants had a higher prevalence of hypertension (OR 2.00, 95% CI 1.39-2.90) and cardiovascular disease (CVD) (OR 1.70, 95% CI 1.11-2.61) compared with the reference group. Insomnia-alone and OSA-alone were associated with higher risk of hypertension but not CVD compared with the reference group. Compared with the reference group, COMISA was associated with a 47% (hazard ratio 1.47, 95% CI 1.06-2.07) increased risk of mortality. The association between COMISA and mortality was consistent across multiple definitions of OSA and insomnia. CONCLUSIONS: COMISA was associated with higher rates of hypertension and CVD at baseline, and an increased risk of all-cause mortality compared with no insomnia/OSA.
50Exploring the link between comorbid insomnia and sleep apnea (COMISA) and erectile dysfunction: implications for male sexual health.PubMed
Monica Levy Andersen, David Gozal, Sergio Tufik
Sex Med Rev. 2025 Jan 31;13(1):105-115. doi: 10.1093/sxmrev/qeae068.
INTRODUCTION: This review explores the interplay between comorbid insomnia and sleep apnea (COMISA) and erectile dysfunction (ED), 2 conditions that significantly impact men's health. COMISA, a recently recognized condition characterized by the coexistence of insomnia and obstructive sleep apnea, has been shown to disrupt sleep architecture and cause intermittent hypoxia. These disturbances are increasingly linked to the exacerbation of ED, a prevalent issue among men. Understanding the connection between COMISA and ED is crucial for developing integrated treatment approaches that address both sleep and sexual health. OBJECTIVES: We aim to explore the epidemiological, physiological, and potential therapeutic intersections of COMISA and ED. This review sets out to develop a better understanding of the relationship between these conditions and to emphasize the need for an integrated diagnostic and therapeutic approach that addresses both sleep and sexual health. METHODS: Through a comprehensive analysis, including a detailed examination of extant studies, we address the hormonal imbalances and alterations in neural pathways that collectively contribute to the complex pathophysiology of ED and how these are particularly susceptible to the concurrent presence of COMISA. RESULTS: Our analysis indicates that disruptions in sleep architecture and intermittent hypoxia associated with COMISA can exacerbate ED. Hormonal imbalances, endothelial dysfunction, autonomic imbalance, and increased inflammation and oxidative stress are key mechanisms through which COMISA influences ED. These factors collectively impair vascular health, reduce testosterone levels, disrupt neural control of erections, and contribute to the severity of ED. CONCLUSIONS: This review underscores the necessity for an integrated approach to diagnosis and therapy that considers both sleep and sexual health to improve overall outcomes. These insights should foster a deeper understanding of the relationship between COMISA and ED, encourage further research in this area, and potentially lead to the development of innovative treatment strategies to manage these closely intertwined health concerns.
51Heart rate variability analysis in comorbid insomnia and sleep apnea (COMISA).PubMed
Adrián Martín-Montero, Fernando Vaquerizo-Villar, Clara García-Vicente, et al.
Sci Rep. 2025 May 21;15(1):17574. doi: 10.1038/s41598-025-02541-7.
Obstructive sleep apnea (OSA) and insomnia are the two most prevalent sleep disorders, often co-occurring in a condition termed comorbid insomnia and sleep apnea (COMISA). While autonomic nervous system (ANS) dysfunction resulting from each of these disorders has been separately established through heart rate variability (HRV) analysis, the specific overnight ANS alterations due to COMISA have not been explored. This study aims to characterize nocturnal ANS alterations attributable to COMISA through time and frequency HRV analysis, distinguishing them from those of isolated insomnia or OSA. A total of 5,335 electrocardiograms from the Sleep Heart Health Study (SHHS) dataset were included in this research. Based on overnight polysomnography and sleep questionnaires, participants were categorized into No-OSA (2,738 subjects), Insomnia (190 subjects), OSA (2,260 subjects), or COMISA (147 subjects) groups. Classic time and frequency HRV features, along with specific frequency measures, were computed to characterize HRV behavior throughout the whole night, in both wakefulness and sleep periods. The analysis revealed that COMISA-specific ANS dysfunction manifests as reduced parasympathetic activity during wakefulness and heightened sympathetic activation during sleep. While primary ANS dysfunctions seem to result from recurrent apneic events affecting frequency features present in both OSA and COMISA, insomnia significantly alters mean heart rate during sleep, thus being the only feature distinguishing these two conditions. In conclusion, the combined effects of OSA and insomnia induce specific ANS dysfunction at night, highlighting the need for further HRV studies to better understand the impact of COMISA on ANS and its cardiovascular implications.Clinical trial registration: The clinical trial identifier of the original SHHS database is NCT00005275, https://sleepdata.org/datasets/shhs .
52Restless legs syndrome and periodic limb movements during sleep: diagnosis and treatment.PubMed
Mehmet Karatas
Neurologist. 2007 Sep;13(5):294-301. doi: 10.1097/NRL.0b013e3181422589.
BACKGROUND: Restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS) have been known for over 300 years, and they may be present in as many as 25% of patients who have sleep disorders. These patients generally present with insomnia. These disorders often remain undiagnosed for an average of 16 years and patients have seen an average of 13 physicians for their symptoms. Therefore, these disorders merit the attention and interest of the practitioner, so that such patients can be evaluated and treated without delay. REVIEW SUMMARY: The important features of these disorders are the following: (1) their recognition since 1685, (2) they may comprise up to 25% of all sleep disorders, (3) they require differentiation from many other disorders, and (4) effective treatment is available. Although it is believed that RLS and PLMS are 2 clinical manifestations of the same central nervous system dysfunction, they are generally discussed separately, as different nosological entities. CONCLUSION: RLS and PLMS are common neurologic disorders and increase in prevalence with aging. These disorders can be disabling conditions, causing sleep disturbance at night and excessive sleepiness during the day. Polysomnography and the suggested immobilization test are used to support the clinical diagnosis of RLS and PLMS. Although levodopa alleviates symptoms, rebound and augmentation occur frequently, limiting the long-term usefulness of this agent. The direct dopamine receptor agonists such as pergolide, pramipexole, ropinirole, and cabergoline have largely replaced levodopa as the most effective treatment for RLS and PLMS.
53Insomnia.PubMed
Eliza L Sutton
Med Clin North Am. 2014 May;98(3):565-81. doi: 10.1016/j.mcna.2014.01.008.
Insomnia, as the term is used by patients and in primary care, is a symptom: dissatisfaction with the quality or quantity of sleep obtained, despite attempts. For acute insomnia, reversal of the trigger (if possible) and treatment with safe, effective sleep medication are advised. For chronic insomnia, as with other types of symptoms, trying to distinguish between several potential underlying causes is key, because no single treatment approach is appropriate for all situations. Specific conditions such as restless legs syndrome, circadian rhythm disorders, and sleep apnea have specific treatment approaches.
54Narcolepsy.PubMed
Lucie Barateau, Fabio Pizza, Giuseppe Plazzi, et al.
J Sleep Res. 2022 Aug;31(4):e13631. doi: 10.1111/jsr.13631. Epub 2022 May 27.
This article addresses the clinical presentation, diagnosis, pathophysiology and management of narcolepsy type 1 and 2, with a focus on recent findings. A low level of hypocretin-1/orexin-A in the cerebrospinal fluid is sufficient to diagnose narcolepsy type 1, being a highly specific and sensitive biomarker, and the irreversible loss of hypocretin neurons is responsible for the main symptoms of the disease: sleepiness, cataplexy, sleep-related hallucinations and paralysis, and disrupted nocturnal sleep. The process responsible for the destruction of hypocretin neurons is highly suspected to be autoimmune, or dysimmune. Over the last two decades, remarkable progress has been made for the understanding of these mechanisms that were made possible with the development of new techniques. Conversely, narcolepsy type 2 is a less well-defined disorder, with a variable phenotype and evolution, and few reliable biomarkers discovered so far. There is a dearth of knowledge about this disorder, and its aetiology remains unclear and needs to be further explored. Treatment of narcolepsy is still nowadays only symptomatic, targeting sleepiness, cataplexy and disrupted nocturnal sleep. However, new psychostimulants have been recently developed, and the upcoming arrival of non-peptide hypocretin receptor-2 agonists should be a revolution in the management of this rare sleep disease, and maybe also for disorders beyond narcolepsy.
55Sleep disturbance and psychiatric disorders.PubMed
Daniel Freeman, Bryony Sheaves, Felicity Waite, et al.
Lancet Psychiatry. 2020 Jul;7(7):628-637. doi: 10.1016/S2215-0366(20)30136-X.
Signs of mental ill health that cut across psychiatric diagnostic categories at high rates are typically viewed as non-specific occurrences, downgraded in importance and disregarded. However, problems not associated with particular diagnoses should be expected if there is shared causation across mental health conditions. If dynamic networks of interacting symptoms are the reality of mental health presentations, then particularly disruptive and highly connected problems should be especially common. The non-specific occurrence might be highly consequential. One non-specific occurrence that is often overlooked is patients' chronic difficulty in getting good sleep. In this Review, we consider whether disrupted sleep might be a contributory causal factor in the occurrence of major types of mental health disorders. It is argued that insomnia and other mental health conditions not only share common causes but also show a bidirectional relationship, with typically the strongest pathway being disrupted sleep as a causal factor in the occurrence of other psychiatric problems. Treating insomnia lessens other mental health problems. Intervening on sleep at an early stage might be a preventive strategy for the onset of clinical disorders. Our recommendations are that insomnia is assessed routinely in the occurrence of mental health disorders; that sleep disturbance is treated in services as a problem in its own right, yet also recognised as a pathway to reduce other mental health difficulties; and that access to evidence-based treatment for sleep difficulties is expanded in mental health services.
56Cognitive behavioral therapy for insomnia in patients with mental disorders and comorbid insomnia: A systematic review and meta-analysis.PubMed
Elisabeth Hertenstein, Ersilia Trinca, Marina Wunderlin, et al.
Sleep Med Rev. 2022 Apr;62:101597. doi: 10.1016/j.smrv.2022.101597. Epub 2022 Feb 9.
Almost 70% of patients with mental disorders report sleep difficulties and 30% fulfill the criteria for insomnia disorder. Cognitive behavioral therapy for insomnia (CBT-I) is the first-line treatment for insomnia according to current treatment guidelines. Despite this circumstance, insomnia is frequently treated only pharmacologically especially in patients with mental disorders. The aim of the present meta-analysis was to quantify the effects of CBT-I in patients with mental disorders and comorbid insomnia on two outcome parameters: the severity of insomnia and mental health. The databases PubMed, CINHAL (Ebsco) und PsycINFO (Ovid) were searched for randomized controlled trials on adult patients with comorbid insomnia and any mental disorder comparing CBT-I to placebo, waitlist or treatment as usual using self-rating questionnaires as outcomes for either insomnia or mental health or both. The search resulted in 1994 records after duplicate removal of which 22 fulfilled the inclusion criteria and were included for the meta-analysis. The comorbidities were depression (eight studies, 491 patients), post-traumatic stress disorder (PTSD, four studies, 216 patients), alcohol dependency (three studies, 79 patients), bipolar disorder (one study, 58 patients), psychosis (one study, 50 patients) and mixed comorbidities within one study (five studies, 189 patients). The effect sizes for the reduction of insomnia severity post treatment were 0.5 (confidence interval, CI, 0.3-0.8) for patients with depression, 1.5 (CI 1.0-1.9) for patients with PTSD, 1.4 (CI 0.9-1.9) for patients with alcohol dependency, 1.2 (CI 0.8-1.7) for patients with psychosis/bipolar disorder, and 0.8 (CI 0.1-1.6) for patients with mixed comorbidities. Effect sizes for the reduction of insomnia severity were moderate to large at follow-up. Regarding the effects on comorbid symptom severity, effect sizes directly after treatment were 0.5 (CI 0.1-0.8) for depression, 1.3 (CI 0.6-1.9) for PTSD, 0.9 (CI 0.3-1.4) for alcohol dependency in only one study, 0.3 (CI -0.1 - 0.7, insignificant) for psychosis/bipolar, and 0.8 (CI 0.1-1.5) for mixed comorbidities. There were no significant effects on comorbid symptoms at follow-up. Together, these significant, stable medium to large effects indicate that CBT-I is an effective treatment for patients with insomnia and a comorbid mental disorder, especially depression, PTSD and alcohol dependency. CBT-I is also an effective add-on treatment with the aim of improving mental health in patients with depression, PTSD, and symptom severity in outpatients with mixed diagnoses. Thus, in patients with mental disorders and comorbid insomnia, given the many side effects of medication, CBT-I should be considered as a first-line treatment.
57The Many Faces of Sleep Disorders in Post-Traumatic Stress Disorder: An Update on Clinical Features and Treatment.PubMed
Franziska C Weber, Thomas C Wetter
Neuropsychobiology. 2022;81(2):85-97. doi: 10.1159/000517329. Epub 2021 Sep 2.
Sleep disorders and nightmares are core symptoms of post-traumatic stress disorder (PTSD). The relationship seems to be bidirectional, and persistent disturbed sleep may influence the course of the disorder. With regard to sleep quality, insomnia and nocturnal anxiety symptoms, as well as nightmares and stressful dreams, are the most prominent sleep symptoms. Polysomnographic measurements reveal alterations of the sleep architecture and fragmentation of rapid eye movement sleep. In addition, sleep disorders, such as sleep-related breathing disorders and parasomnias are frequent comorbid conditions. The complex etiology and symptomatology of trauma-related sleep disorders with frequent psychiatric comorbidity require the application of multimodal treatment concepts, including psychological and pharmacological interventions. However, there is little empirical evidence on the effectiveness of long-term drug treatment for insomnia and nightmares. For nondrug interventions, challenges arise from the current lack of PTSD-treatment concepts integrating sleep- and trauma-focused therapies. Effective therapy for sleep disturbances may consequently also improve well-being during the day and probably even the course of PTSD. Whether early sleep interventions exert a preventive effect on the development of PTSD remains to be clarified in future studies.
58Sleep disturbances, TBI and PTSD: Implications for treatment and recovery.PubMed
Karina Stavitsky Gilbert, Sarah M Kark, Philip Gehrman, et al.
Clin Psychol Rev. 2015 Aug;40:195-212. doi: 10.1016/j.cpr.2015.05.008. Epub 2015 Jun 3.
Post-Traumatic Stress Disorder (PTSD), traumatic brain injury (TBI), and sleep problems significantly affect recovery and functional status in military personnel and Veterans returning from combat. Despite recent attention, sleep is understudied in the Veteran population. Few treatments and rehabilitation protocols target sleep, although poor sleep remains at clinical levels and continues to adversely impact functioning even after the resolution of PTSD or mild TBI symptoms. Recent developments in non-pharmacologic sleep treatments have proven efficacious as stand-alone interventions and have potential to improve treatment outcomes by augmenting traditional behavioral and cognitive therapies. This review discusses the extensive scope of work in the area of sleep as it relates to TBI and PTSD, including pathophysiology and neurobiology of sleep; existing and emerging treatment options; as well as methodological issues in sleep measurements for TBI and PTSD. Understanding sleep problems and their role in the development and maintenance of PTSD and TBI symptoms may lead to improvement in overall treatment outcomes while offering a non-stigmatizing entry in mental health services and make current treatments more comprehensive by helping to address a broader spectrum of difficulties.
59Post-traumatic stress disorder symptoms and quality of life among older patients with cancer during the COVID-19 pandemic.PubMed
Francois Cherifi, François Gernier, Fabrice Jardin, et al.
J Geriatr Oncol. 2023 Nov;14(8):101634. doi: 10.1016/j.jgo.2023.101634. Epub 2023 Sep 25.
INTRODUCTION: The Coronavirus (COVID-19) pandemic and its associated health restrictions have harmed the population psychologically. We aimed to compare the post-traumatic stress disorder (PTSD) symptoms and Quality of Life (QoL) in older French patients with cancer to the younger ones. MATERIALS AND METHODS: This longitudinal multicenter study named COVIPACT began in April 2020 during the first French lockdown and has included 579 outpatients receiving treatment for a solid or hematological malignancy. Data were collected every three months, namely at the first release period (M3), at the second lockdown (M6), at the second release period (M9), and finally at the last curfew period (M12) in France. Standardized validated self-questionnaires were used to assess PTSD symptoms (using the Event Scale-Revised self-questionnaire), insomnia (through the Insomnia Severity Index questionnaire), QoL (using the Functional Assessment of Cancer Therapy - General questionnaire), and cognitive complaints (through the Functional Assessment of Cancer Therapy - Cognition questionnaire). Student (or Wilcoxon) tests and Chi-squared tests were used for continuous or discrete variables, respectively. We conducted linear mixed model to study the change during follow-up. RESULTS: Out of 579 included patients, 157 (27%) were ≥ 70 years old at baseline, of whom 104 participated in the longitudinal study. At baseline, older patients reported fewer PTSD symptoms (17% versus 23%, p = .06), insomnia (17% versus 27%, p = .02), and cognitive complaint (3% versus 16%, p < .01) than younger patients. QoL at baseline was similar between age subgroups. We observed no significant difference in the trajectory of PTSD symptoms, insomnia, or emotional well-being between both groups during the follow-up. Cognitive complaints were lower at baseline in older patients but steadily increased during the follow-up and reached the same level as younger patients at one year. DISCUSSION: One in five older patients reported PTSD symptoms, evolving similarly to younger patients during the first year of the COVID-19 pandemic. While cognitive complaints tend to recover in a bell-shaped curve at one year in younger patients, the trend is increasing in older ones. Screening for PTSD symptoms and late cognitive impairment should be given special attention in older patients. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04366154.
60Posttraumatic Stress Symptoms in Patients With Cancer During the COVID-19 Pandemic: A One-Year Longitudinal Study.PubMed
Etienne Bastien, Sophie Lefèvre-Arbogast, Justine Lequesne, et al.
J Natl Compr Canc Netw. 2023 Feb 22;21(3):265-272.e7. doi: 10.6004/jnccn.2023.7085.
BACKGROUND: Patients with cancer may be particularly vulnerable to psychological consequences of the COVID-19 pandemic. We studied the prevalence and evolution of posttraumatic stress symptoms (PTSS) in patients with cancer during the pandemic waves, and we investigated factors associated with high symptoms. METHODS: COVIPACT is a 1-year longitudinal prospective study of French patients with solid/hematologic malignancies receiving treatment during the first nationwide lockdown. PTSS were measured every 3 months from April 2020 using the Impact of Event Scale-Revised. Patients also completed questionnaires on their quality of life, cognitive complaints, insomnia, and COVID-19 lockdown experience. RESULTS: Longitudinal analyses involved 386 patients with at least one PTSS assessment after baseline (median age, 63 years; 76% female). Among them, 21.5% had moderate/severe PTSS during the first lockdown. The rate of patients reporting PTSS decreased at lockdown release (13.6%), increased again at second lockdown (23.2%), and slightly declined from the second release period (22.7%) to the third lockdown (17.5%). Patients were grouped into 3 trajectories of evolution. Most patients had stable low symptoms throughout the period, 6% had high baseline symptoms slowly decreasing over time, and 17.6% had moderate symptoms worsening during the second lockdown. Female sex, feeling socially isolated, worrying about COVID-19 infection, and using psychotropic drugs were associated with PTSS. PTSS were associated with impaired quality of life, sleep, and cognition. CONCLUSIONS: Approximately one-fourth of patients with cancer experienced high and persistent PTSS over the first year of the COVID-19 pandemic and may benefit from psychological support. CLINICALTRIALS: gov identifier: NCT04366154.
61Sleep Disturbances in Chronic Pain: Neurobiology, Assessment, and Treatment in Physical Therapist Practice.PubMed
Jo Nijs, Olivier Mairesse, Daniel Neu, et al.
Phys Ther. 2018 May 1;98(5):325-335. doi: 10.1093/ptj/pzy020.
Among people with chronic pain, insomnia is highly prevalent, closely related to the mechanism of central sensitization, characterized by low-grade neuroinflammation, and commonly associated with stress or anxiety; in addition, it often does not respond effectively to drug treatments. This review article applies the current understanding of insomnia to clinical practice, including assessment and conservative treatment of insomnia in people with chronic pain. Cognitive-behavioral therapy for insomnia can be efficacious for improvements in sleep initiation, sleep maintenance, perceived sleep quality, and pain interference with daily functioning in people with chronic pain. A recent systematic review concluded that with additional training, physical therapist-led cognitive-behavioral interventions are efficacious for low back pain, allowing their implementation within the field. Cognitive-behavioral therapy for insomnia, as provided to people with chronic pain, typically includes education, sleep restriction measures, stimulus control instructions, sleep hygiene, and cognitive therapy.
62Cognitive Behavioral Therapy for Insomnia in Pain Management for Nonspecific Chronic Spinal Pain: A Randomized Clinical Trial.PubMed
Anneleen Malfliet, Liesbet De Baets, Thomas Bilterys, et al.
JAMA Netw Open. 2024 Aug 1;7(8):e2425856. doi: 10.1001/jamanetworkopen.2024.25856.
IMPORTANCE: Insomnia is highly prevalent in patients with nonspecific chronic spinal pain (nCSP). Given the close interaction between insomnia and pain, targeting sleep problems during therapy could improve treatment outcomes. OBJECTIVE: To evaluate the effectiveness of cognitive behavioral therapy for insomnia (CBTi) integrated in best-evidence pain management (BEPM) vs BEPM only in patients with nCSP and insomnia. DESIGN, SETTING, AND PARTICIPANTS: A multicenter randomized clinical trial with 1-year follow-up was conducted between April 10, 2018, and April 30, 2022. Data and statistical analysis were performed between May 1, 2022, and April 24, 2023. Patients with nCSP and insomnia were evaluated using self-report and at-home polysomnography, to exclude underlying sleep pathologic factors. Participants were treated at the University Hospital Brussels or University Hospital Ghent, Belgium. Intention-to-treat analysis was performed. INTERVENTIONS: Participants were randomized to either CBTi-BEPM or BEPM only. Both groups received 18 treatment sessions over 14 weeks. The CBTi-BEPM treatment included 6 CBTi sessions and 12 BEPM sessions. The BEPM treatment included pain neuroscience education (3 sessions) and exercise therapy (9 sessions in the CBTi-BEPM group, 15 sessions in the BEPM-only group). MAIN OUTCOMES AND MEASURES: The primary outcome was change in mean pain intensity (assessed with Brief Pain Inventory [BPI]) at 12 months after the intervention. Exploratory secondary outcomes included several pain- and sleep-related outcomes. Blinded outcome assessment took place at baseline, posttreatment, and at 3-, 6-, and 12-month follow-up. RESULTS: A total of 123 patients (mean [SD] age, 40.2 [11.18] years; 84 women [68.3%]) were included in the trial. In 99 participants (80.5%) with 12-month BPI data, the mean pain intensity at 12 months decreased by 1.976 points (reduction of 40%) in the CBTi-BEPM group and 1.006 points (reduction of 24%) points in the BEPM-only group. At 12 months, there was no significant difference in pain intensity change between groups (mean group difference, 0.970 points; 95% CI, -0.051 to 1.992; Cohen d, 2.665). Treatment with CBTi-BEPM resulted in a response for BPI average pain with a number needed to treat (NNT) of 4 observed during 12 months. On a preliminary basis, CBTi-BEPM was, consistently over time and analyses, more effective than BEPM only for improving insomnia severity (Cohen d, 4.319-8.961; NNT for response ranging from 2 to 4, and NNT for remission ranging from 5 to 12), sleep quality (Cohen d, 3.654-6.066), beliefs about sleep (Cohen d, 5.324-6.657), depressive symptoms (Cohen d, 2.935-3.361), and physical fatigue (Cohen d, 2.818-3.770). No serious adverse effects were reported. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, adding CBTi to BEPM did not further improve pain intensity reduction for patients with nCSP and comorbid insomnia more than BEPM alone. Yet, as CBTi-BEPM led to significant and clinically important changes in insomnia severity and sleep quality, CBTi integrated in BEPM should be considered in the treatment of patients with nCSP and comorbid insomnia. Further research can investigate the patient characteristics that moderate the response to CBTi-BEPM in terms of pain-related outcomes, as understanding of these moderators may be of utmost clinical importance. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT03482856.
63Anterior cingulate cortex projections to the dorsal medial striatum underlie insomnia associated with chronic pain.PubMed
Ya-Dong Li, Yan-Jia Luo, Wei-Kun Su, et al.
Neuron. 2024 Apr 17;112(8):1328-1341.e4. doi: 10.1016/j.neuron.2024.01.014. Epub 2024 Feb 13.
Chronic pain often leads to the development of sleep disturbances. However, the precise neural circuit mechanisms responsible for sleep disorders in chronic pain have remained largely unknown. Here, we present compelling evidence that hyperactivity of pyramidal neurons (PNs) in the anterior cingulate cortex (ACC) drives insomnia in a mouse model of nerve-injury-induced chronic pain. After nerve injury, ACC PNs displayed spontaneous hyperactivity selectively in periods of insomnia. We then show that ACC PNs were both necessary for developing chronic-pain-induced insomnia and sufficient to mimic sleep loss in naive mice. Importantly, combining optogenetics and electrophysiological recordings, we found that the ACC projection to the dorsal medial striatum (DMS) underlies chronic-pain-induced insomnia through enhanced activity and plasticity of ACC-DMS dopamine D1R neuron synapses. Our findings shed light on the pivotal role of ACC PNs in developing chronic-pain-induced sleep disorders.
64Pain and Analgesic Related Insomnia.PubMed
Jana Mlíchová, Zoltán Paluch, Ondřej Šimandl
Pain Manag Nurs. 2023 Jun;24(3):254-264. doi: 10.1016/j.pmn.2022.11.002. Epub 2022 Dec 19.
OBJECTIVES: The aim of this review is to describe the effects of analgesics on sleep. DATA SOURCES: Systematic search of the databases of PubMed and the Cochrane Library was performed between January and September 2021. REVIEW/ANALYSIS METHODS: The search included all articles on the topic published during the past 20 years (2000-2020). The search strategy was developed using a controlled vocabulary of known studies meeting the inclusion criteria and focused on the following terms: chronic pain, pain, sleep disturbance, insomnia, analgesic, analgesic medication, antidepressants, antiepileptic drugs, nonsteroidal drugs, opioids, and quality of life. Two reviewers independently considered the studies for inclusion in the review, assessed the risk of bias, and extracted data. DESIGN: Review and analysis. RESULTS: A total of 37 studies met the inclusion criteria: 15 analyzed the effects of opioids, 6 those of nonsteroidal anti-inflammatory drugs and acetaminophen, and 16 the effects of adjuvant analgesics. CONCLUSIONS: Sleep quality may be adversely affected by a variety of medications used in clinical practice, including those used in analgesic indications. The class of analgesics most affecting sleep quality are opioids.
65Cancer-related insomnia.PubMed
Raghava R Induru, Declan Walsh
Am J Hosp Palliat Care. 2014 Nov;31(7):777-85. doi: 10.1177/1049909113508302. Epub 2013 Oct 17.
Insomnia increases cancer symptom burden and impairs quality of life. The lack of standard definitions and treatment guidelines makes management difficult. Insomnia is common in most cancers but appears particularly so in lung, breast, and head and neck tumors. Older women seem most susceptible. Insomnia not only affects patients with cancer but also caregivers and families. Systematic screening is important. Few validated assessment scales are available. Nonpharmacologic therapies like cognitive behavioral therapy may help. New nonbenzodiazepine hypnotics may have some therapeutic advantages over older agents. Management of associated or contributory symptoms like fatigue, pain, and hot flashes with appropriate symptom-specific agents is important. Successful management may have a significant positive impact on global quality of life.
66Insomnia in adult patients with cancer: ESMO Clinical Practice Guideline.PubMed
L Grassi, R Zachariae, R Caruso, et al.
ESMO Open. 2023 Dec;8(6):102047. doi: 10.1016/j.esmoop.2023.102047. Epub 2023 Nov 21.
• Insomnia is common in patients with cancer, with a higher prevalence than observed in the general population. • Insomnia is often under-recognised and inadequately treated in patients with cancer. • Brief validated screening tools are available for the evaluation of insomnia in clinical practice. • First-line therapy should be based on international guidelines recommending cognitive behavioural therapy for insomnia.
67Impact of insomnia on ovarian cancer risk and survival: a Mendelian randomization study.PubMed
Heming Wang, Brett M Reid, Rebecca C Richmond, et al.
EBioMedicine. 2024 Jun;104:105175. doi: 10.1016/j.ebiom.2024.105175. Epub 2024 Jun 1.
BACKGROUND: Insomnia is the most common sleep disorder in patients with epithelial ovarian cancer (EOC). We investigated the causal association between genetically predicted insomnia and EOC risk and survival through a two-sample Mendelian randomization (MR) study. METHODS: Insomnia was proxied using genetic variants identified in a genome-wide association study (GWAS) meta-analysis of UK Biobank and 23andMe. Using genetic associations with EOC risk and overall survival from the Ovarian Cancer Association Consortium (OCAC) GWAS in 66,450 women (over 11,000 cases with clinical follow-up), we performed Iterative Mendelian Randomization and Pleiotropy (IMRP) analysis followed by a set of sensitivity analyses. Genetic associations with survival and response to treatment in ovarian cancer study of The Cancer Genome Atlas (TCGA) were estimated controlling for chemotherapy and clinical factors. FINDINGS: Insomnia was associated with higher risk of endometrioid EOC (OR = 1.60, 95% CI 1.05-2.45) and lower risk of high-grade serous EOC (HGSOC) and clear cell EOC (OR = 0.79 and 0.48, 95% CI 0.63-1.00 and 0.27-0.86, respectively). In survival analysis, insomnia was associated with shorter survival of invasive EOC (OR = 1.45, 95% CI 1.13-1.87) and HGSOC (OR = 1.4, 95% CI 1.04-1.89), which was attenuated after adjustment for body mass index and reproductive age. Insomnia was associated with reduced survival in TCGA HGSOC cases who received standard chemotherapy (OR = 2.48, 95% CI 1.13-5.42), but was attenuated after adjustment for clinical factors. INTERPRETATION: This study supports the impact of insomnia on EOC risk and survival, suggesting treatments targeting insomnia could be pivotal for prevention and improving patient survival. FUNDING: National Institutes of Health, National Cancer Institute. Full funding details are provided in acknowledgments.
68Undiagnosed and comorbid disorders in patients with presumed chronic fatigue syndrome.PubMed
An Mariman, Liesbeth Delesie, Els Tobback, et al.
J Psychosom Res. 2013 Nov;75(5):491-6. doi: 10.1016/j.jpsychores.2013.07.010. Epub 2013 Aug 20.
OBJECTIVE: To assess undiagnosed and comorbid disorders in patients referred to a tertiary care center with a presumed diagnosis of chronic fatigue syndrome (CFS). METHODS: Patients referred for chronic unexplained fatigue entered an integrated diagnostic pathway, including internal medicine assessment, psychodiagnostic screening, physiotherapeutic assessment and polysomnography+multiple sleep latency testing. Final diagnosis resulted from a multidisciplinary team discussion. Fukuda criteria were used for the diagnosis of CFS, DSM-IV-TR criteria for psychiatric disorders, ICSD-2 criteria for sleep disorders. RESULTS: Out of 377 patients referred, 279 (74.0%) were included in the study [84.9% female; mean age 38.8years (SD 10.3)]. A diagnosis of unequivocal CFS was made in 23.3%. In 21.1%, CFS was associated with a sleep disorder and/or psychiatric disorder, not invalidating the diagnosis of CFS. A predominant sleep disorder was found in 9.7%, 19.0% had a psychiatric disorder and 20.8% a combination of both. Only 2.2% was diagnosed with a classical internal disease. In the total sample, a sleep disorder was found in 49.8%, especially obstructive sleep apnea syndrome, followed by psychophysiologic insomnia and periodic limb movement disorder. A psychiatric disorder was diagnosed in 45.2%; mostly mood and anxiety disorder. CONCLUSIONS: A multidisciplinary approach to presumed CFS yields unequivocal CFS in only a minority of patients, and reveals a broad spectrum of exclusionary or comorbid conditions within the domains of sleep medicine and psychiatry. These findings favor a systematic diagnostic approach to CFS, suitable to identify a wide range of diagnostic categories that may be subject to dedicated care.
69Insomnia in the Older Adult.PubMed
Glenna S Brewster, Barbara Riegel, Philip R Gehrman
Sleep Med Clin. 2022 Jun;17(2):233-239. doi: 10.1016/j.jsmc.2022.03.004.
Although insomnia is not a normal part of the aging process, its prevalence increases with age. Factors such as medications and medical and psychiatric disorders can increase the risk for insomnia. In order to diagnose insomnia, it is important for older adults to complete comprehensive sleep and health histories. Cognitive behavioral therapy for insomnia, which includes stimulus control, sleep restriction, sleep hygiene, and cognitive therapy, is the recommended first-line treatment of insomnia and is more effective that medications for the long-term management of insomnia. Medications such as benzodiazepines and antidepressants should be avoided for the treatment of insomnia in older adults.
70Behavioral and psychological treatments for chronic insomnia disorder in adults: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.PubMed
Jack D Edinger, J Todd Arnedt, Suzanne M Bertisch, et al.
J Clin Sleep Med. 2021 Feb 1;17(2):263-298. doi: 10.5664/jcsm.8988.
INTRODUCTION: The purpose of this systematic review is to provide supporting evidence for a clinical practice guideline on the use of behavioral and psychological treatments for chronic insomnia disorder in adult populations. METHODS: The American Academy of Sleep Medicine commissioned a task force of 9 experts in sleep medicine and sleep psychology. A systematic review was conducted to identify randomized controlled trials that addressed behavioral and psychological interventions for the treatment of chronic insomnia disorder in adults. Statistical analyses were performed to determine if the treatments produced clinically significant improvements in a range of critical and important outcomes. Finally, the Grading of Recommendations Assessment, Development, and Evaluation process was used to evaluate the evidence for making specific treatment recommendations. RESULTS: The literature search identified 1,244 studies; 124 studies met the inclusion criteria, and 89 studies provided data suitable for statistical analyses. Evidence for the following interventions is presented in this review: cognitive-behavioral therapy for insomnia, brief therapies for insomnia, stimulus control, sleep restriction therapy, relaxation training, sleep hygiene, biofeedback, paradoxical intention, intensive sleep retraining, and mindfulness. This review provides a detailed summary of the evidence along with the quality of evidence, the balance of benefits vs harms, patient values and preferences, and resource use considerations.
71Cognitive Behavioral Therapy for Chronic Insomnia: A Systematic Review and Meta-analysis.PubMed
James M Trauer, Mary Y Qian, Joseph S Doyle, et al.
Ann Intern Med. 2015 Aug 4;163(3):191-204. doi: 10.7326/M14-2841.
BACKGROUND: Because psychological approaches are likely to produce sustained benefits without the risk for tolerance or adverse effects associated with pharmacologic approaches, cognitive behavioral therapy for insomnia (CBT-i) is now commonly recommended as first-line treatment for chronic insomnia. PURPOSE: To determine the efficacy of CBT-i on diary measures of overnight sleep in adults with chronic insomnia. DATA SOURCES: Searches of MEDLINE, EMBASE, PsycINFO, CINAHL, the Cochrane Library, and PubMed Clinical Queries from inception to 31 March 2015, supplemented with manual screening. STUDY SELECTION: Randomized, controlled trials assessing the efficacy of face-to-face, multimodal CBT-i compared with inactive comparators on overnight sleep in adults with chronic insomnia. Studies of insomnia comorbid with medical, sleep, or psychiatric disorders were excluded. DATA EXTRACTION: Study characteristics, quality, and data were assessed independently by 2 reviewers. Main outcome measures were sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), and sleep efficiency (SE%). DATA SYNTHESIS: Among 292 citations and 91 full-text articles reviewed, 20 studies (1162 participants [64% female; mean age, 56 years]) were included. Approaches to CBT-i incorporated at least 3 of the following: cognitive therapy, stimulus control, sleep restriction, sleep hygiene, and relaxation. At the posttreatment time point, SOL improved by 19.03 (95% CI, 14.12 to 23.93) minutes, WASO improved by 26.00 (CI, 15.48 to 36.52) minutes, TST improved by 7.61 (CI, -0.51 to 15.74) minutes, and SE% improved by 9.91% (CI, 8.09% to 11.73%). Changes seemed to be sustained at later time points. No adverse outcomes were reported. LIMITATION: Narrow inclusion criteria limited applicability to patients with comorbid insomnia and other sleep problems, and accuracy of estimates at later time points was less clear. CONCLUSION: CBT-i is an effective treatment for adults with chronic insomnia, with clinically meaningful effect sizes. PRIMARY FUNDING SOURCE: None. (PROSPERO registration number: CRD42012002863).
72Acupuncture Versus Cognitive Behavioral Therapy for Insomnia in Cancer Survivors: A Randomized Clinical Trial.PubMed
Sheila N Garland, Sharon X Xie, Kate DuHamel, et al.
J Natl Cancer Inst. 2019 Dec 1;111(12):1323-1331. doi: 10.1093/jnci/djz050.
BACKGROUND: Insomnia is a common and debilitating disorder experienced by cancer survivors. Although cancer survivors express a preference for using nonpharmacological treatment to manage insomnia, the comparative effectiveness between acupuncture and Cognitive Behavioral Therapy for Insomnia (CBT-I) for this disorder is unknown. METHODS: This randomized trial compared 8 weeks of acupuncture (n = 80) and CBT-I (n = 80) in cancer survivors. Acupuncture involved stimulating specific points on the body with needles. CBT-I included sleep restriction, stimulus control, cognitive restructuring, relaxation training, and education. We measured insomnia severity (primary outcome), pain, fatigue, mood, and quality of life posttreatment (8 weeks) with follow-up until 20 weeks. We used linear mixed-effects models for analyses. All statistical tests were two-sided. RESULTS: The mean age was 61.5 years and 56.9% were women. CBT-I was more effective than acupuncture posttreatment (P < .001); however, both acupuncture and CBT-I produced clinically meaningful reductions in insomnia severity (acupuncture: -8.31 points, 95% confidence interval = -9.36 to -7.26; CBT-I: -10.91 points, 95% confidence interval = -11.97 to -9.85) and maintained improvements up to 20 weeks. Acupuncture was more effective for pain at the end of treatment; both groups had similar improvements in fatigue, mood, and quality of life and reduced prescription hypnotic medication use. CBT-I was more effective for those who were male (P < .001), white (P = .003), highly educated (P < .001), and had no pain at baseline (P < .001). CONCLUSIONS: Although both treatments produced meaningful and durable improvements, CBT-I was more effective and should be the first line of therapy. The relative differences in the comparative effectiveness between the two interventions for specific groups should be confirmed in future adequately powered trials to guide more tailored interventions for insomnia.
73[Insomnia in psychiatry and psychotherapy].PubMed
Elisabeth Hertenstein, Lampros Perogamvros, Carlotta L Schneider, et al.
Rev Med Suisse. 2023 Sep 20;19(842):1686-1689. doi: 10.53738/REVMED.2023.19.842.1686.
Insomnia disorder is characterized by disturbed sleep continuity and associated daytime impairment. Insomnia is frequent in patients with psychiatric disorders ; 30-40% fulfill the criteria for insomnia disorder as a comorbidity. According to current guidelines, cognitive behavioral therapy for insomnia (CBT-I) is the first-line treatment, comprising sleep education, bedtime restriction, relaxation and cognitive restructuring. Despite guideline recommendations, CBT-I is insufficiently implemented, and insomnia is frequently over-treated with hypnotics. 'Become your own SLEEPexpert' is a behavioral treatment program based on CBT-I with the aim of empowering patients to take care of their own sleep health.
74The efficacy of cognitive and behavior therapies for insomnia on daytime symptoms: A systematic review and network meta-analysis.PubMed
Fee Benz, Teresa Knoop, Andrea Ballesio, et al.
Clin Psychol Rev. 2020 Aug;80:101873. doi: 10.1016/j.cpr.2020.101873. Epub 2020 Jun 5.
Insomnia disorder, defined by nocturnal and daytime symptoms, is highly prevalent worldwide and is associated with the onset of mental illness. Although daytime symptoms are often the reason insomnia patients seek help, it is not clear whether recommended treatment is effective on daytime symptoms. We aimed to investigate the efficacy of cognitive and behavior therapies for insomnia (CBT-I) on all daytime symptoms explored in the literature using both direct and indirect data. 86 studies (15,578 participants) met inclusion criteria. Results showed significant effects of CBT-I administered face-to-face individually, in group and different self-help settings on depressive symptoms, anxiety, daytime sleepiness, fatigue, quality of life, daytime and social functioning and mental state, with Cohen's d's ranging from -0.52 and 0.81. Our results suggest that CBT-I is effective in the treatment of daytime symptoms, albeit with predominantly small to moderate effects compared to far stronger effects on the core symptoms of insomnia. Effects may be biased for depressive and anxiety symptoms, since many included studies excluded patients with severe levels of these complaints. Further, small to moderate effects may reflect that CBT-I, by improving nighttime symptoms, has a positive effect on daytime symptoms, but it does not target the daytime symptoms directly. Future studies may benefit from adding therapeutic techniques that address daytime symptoms more directly.
75The effectiveness of behavioural and cognitive behavioural therapies for insomnia on depressive and fatigue symptoms: A systematic review and network meta-analysis.PubMed
Andrea Ballesio, Maria Raisa Jessica V Aquino, Bernd Feige, et al.
Sleep Med Rev. 2018 Feb;37:114-129. doi: 10.1016/j.smrv.2017.01.006. Epub 2017 Feb 7.
This review aimed to assess the impact of behavioural therapy for insomnia administered alone (BT-I) or in combination with cognitive techniques (cognitive-behavioural therapy for insomnia, CBT-I) on depressive and fatigue symptoms using network meta-analysis. PubMed, Scopus and Web of Science were searched from 1986 to May 2015. Studies were included if they incorporated sleep restriction, a core technique of BT-I treatment, and an adult insomnia sample, a control group and a standardised measure of depressive and/or fatigue symptoms. Face-to-face, group, self-help and internet therapies were all considered. Forty-seven studies were included in the meta-analysis. Eleven classes of treatment or control conditions were identified in the network. Cohen's d at 95% confidence interval (CI) was calculated to assess the effect sizes of each treatment class as compared with placebo. Results showed significant effects for individual face-to-face CBT-I on depressive (d = 0.34, 95% CI: 0.06-0.63) but not on fatigue symptoms, with high heterogeneity between studies. The source of heterogeneity was not identified even after including sex, age, comorbidity and risk of bias in sensitivity analyses. Findings highlight the need to reduce variability between study methodologies and suggest potential effects of individual face-to-face CBT-I on daytime symptoms.
76Clinical and cost-effectiveness of nurse-delivered sleep restriction therapy for insomnia in primary care (HABIT): a pragmatic, superiority, open-label, randomised controlled trial.PubMed
Simon D Kyle, A Niroshan Siriwardena, Colin A Espie, et al.
Lancet. 2023 Sep 16;402(10406):975-987. doi: 10.1016/S0140-6736(23)00683-9. Epub 2023 Aug 10.
BACKGROUND: Insomnia is prevalent and distressing but access to the first-line treatment, cognitive behavioural therapy (CBT), is extremely limited. We aimed to assess the clinical and cost-effectiveness of sleep restriction therapy, a key component of CBT, which has the potential to be widely implemented. METHODS: We did a pragmatic, superiority, open-label, randomised controlled trial of sleep restriction therapy versus sleep hygiene. Adults with insomnia disorder were recruited from 35 general practices across England and randomly assigned (1:1) using a web-based randomisation programme to either four sessions of nurse-delivered sleep restriction therapy plus a sleep hygiene booklet or a sleep hygiene booklet only. There was no restriction on usual care for either group. Outcomes were assessed at 3 months, 6 months, and 12 months. The primary endpoint was self-reported insomnia severity at 6 months measured with the insomnia severity index (ISI). The primary analysis included participants according to their allocated group and who contributed at least one outcome measurement. Cost-effectiveness was evaluated from the UK National Health Service and personal social services perspective and expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. The trial was prospectively registered (ISRCTN42499563). FINDINGS: Between Aug 29, 2018, and March 23, 2020 we randomly assigned 642 participants to sleep restriction therapy (n=321) or sleep hygiene (n=321). Mean age was 55·4 years (range 19-88), with 489 (76·2%) participants being female and 153 (23·8%) being male. 580 (90·3%) participants provided data for at least one outcome measurement. At 6 months, mean ISI score was 10·9 (SD 5·5) for sleep restriction therapy and 13·9 (5·2) for sleep hygiene (adjusted mean difference -3·05, 95% CI -3·83 to -2·28; p<0·0001; Cohen's d -0·74), indicating that participants in the sleep restriction therapy group reported lower insomnia severity than the sleep hygiene group. The incremental cost per QALY gained was £2076, giving a 95·3% probability that treatment was cost-effective at a cost-effectiveness threshold of £20 000. Eight participants in each group had serious adverse events, none of which were judged to be related to intervention. INTERPRETATION: Brief nurse-delivered sleep restriction therapy in primary care reduces insomnia symptoms, is likely to be cost-effective, and has the potential to be widely implemented as a first-line treatment for insomnia disorder. FUNDING: The National Institute for Health and Care Research Health Technology Assessment Programme.
77Components and Delivery Formats of Cognitive Behavioral Therapy for Chronic Insomnia in Adults: A Systematic Review and Component Network Meta-Analysis.PubMed
Yuki Furukawa, Masatsugu Sakata, Ryuichiro Yamamoto, et al.
JAMA Psychiatry. 2024 Apr 1;81(4):357-365. doi: 10.1001/jamapsychiatry.2023.5060.
IMPORTANCE: Chronic insomnia disorder is highly prevalent, disabling, and costly. Cognitive behavioral therapy for insomnia (CBT-I), comprising various educational, cognitive, and behavioral strategies delivered in various formats, is the recommended first-line treatment, but the effect of each component and delivery method remains unclear. OBJECTIVE: To examine the association of each component and delivery format of CBT-I with outcomes. DATA SOURCES: PubMed, Cochrane Central Register of Controlled Trials, PsycInfo, and International Clinical Trials Registry Platform from database inception to July 21, 2023. STUDY SELECTION: Published randomized clinical trials comparing any form of CBT-I against another or a control condition for chronic insomnia disorder in adults aged 18 years and older. Insomnia both with and without comorbidities was included. Concomitant treatments were allowed if equally distributed among arms. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers identified components, extracted data, and assessed trial quality. Random-effects component network meta-analyses were performed. MAIN OUTCOMES AND MEASURES: The primary outcome was treatment efficacy (remission defined as reaching a satisfactory state) posttreatment. Secondary outcomes included all-cause dropout, self-reported sleep continuity, and long-term remission. RESULTS: A total of 241 trials were identified including 31 452 participants (mean [SD] age, 45.4 [16.6] years; 21 048 of 31 452 [67%] women). Results suggested that critical components of CBT-I are cognitive restructuring (remission incremental odds ratio [iOR], 1.68; 95% CI, 1.28-2.20) third-wave components (iOR, 1.49; 95% CI, 1.10-2.03), sleep restriction (iOR, 1.49; 95% CI, 1.04-2.13), and stimulus control (iOR, 1.43; 95% CI, 1.00-2.05). Sleep hygiene education was not essential (iOR, 1.01; 95% CI, 0.77-1.32), and relaxation procedures were found to be potentially counterproductive(iOR, 0.81; 95% CI, 0.64-1.02). In-person therapist-led programs were most beneficial (iOR, 1.83; 95% CI, 1.19-2.81). Cognitive restructuring, third-wave components, and in-person delivery were mainly associated with improved subjective sleep quality. Sleep restriction was associated with improved subjective sleep quality, sleep efficiency, and wake after sleep onset, and stimulus control with improved subjective sleep quality, sleep efficiency, and sleep latency. The most efficacious combination-consisting of cognitive restructuring, third wave, sleep restriction, and stimulus control in the in-person format-compared with in-person psychoeducation, was associated with an increase in the remission rate by a risk difference of 0.33 (95% CI, 0.23-0.43) and a number needed to treat of 3.0 (95% CI, 2.3-4.3), given the median observed control event rate of 0.14. CONCLUSIONS AND RELEVANCE: The findings suggest that beneficial CBT-I packages may include cognitive restructuring, third-wave components, sleep restriction, stimulus control, and in-person delivery but not relaxation. However, potential undetected interactions could undermine the conclusions. Further large-scale, well-designed trials are warranted to confirm the contribution of different treatment components in CBT-I.
78Nurse-delivered sleep restriction therapy to improve insomnia disorder in primary care: the HABIT RCT.PubMed
Simon D Kyle, Peter Bower, Ly-Mee Yu, et al.
Health Technol Assess. 2024 Aug;28(36):1-107. doi: 10.3310/RJYT4275.
BACKGROUND: Insomnia is a prevalent and distressing sleep disorder. Multicomponent cognitive-behavioural therapy is the recommended first-line treatment, but access remains extremely limited, particularly in primary care where insomnia is managed. One principal component of cognitive-behavioural therapy is a behavioural treatment called sleep restriction therapy, which could potentially be delivered as a brief single-component intervention by generalists in primary care. OBJECTIVES: The primary objective of the Health-professional Administered Brief Insomnia Therapy trial was to establish whether nurse-delivered sleep restriction therapy in primary care improves insomnia relative to sleep hygiene. Secondary objectives were to establish whether nurse-delivered sleep restriction therapy was cost-effective, and to undertake a process evaluation to understand intervention delivery, fidelity and acceptability. DESIGN: Pragmatic, multicentre, individually randomised, parallel-group, superiority trial with embedded process evaluation. SETTING: National Health Service general practice in three regions of England. PARTICIPANTS: Adults aged ≥ 18 years with insomnia disorder were randomised using a validated web-based randomisation programme. INTERVENTIONS: Participants in the intervention group were offered a brief four-session nurse-delivered behavioural treatment involving two in-person sessions and two by phone. Participants were supported to follow a prescribed sleep schedule with the aim of restricting and standardising time in bed. Participants were also provided with a sleep hygiene leaflet. The control group received the same sleep hygiene leaflet by e-mail or post. There was no restriction on usual care. MAIN OUTCOME MEASURES: Outcomes were assessed at 3, 6 and 12 months. Participants were included in the primary analysis if they contributed at least one post-randomisation outcome. The primary end point was self-reported insomnia severity with the Insomnia Severity Index at 6 months. Secondary outcomes were health-related and sleep-related quality of life, depressive symptoms, work productivity and activity impairment, self-reported and actigraphy-defined sleep, and hypnotic medication use. Cost-effectiveness was evaluated using the incremental cost per quality-adjusted life-year. For the process evaluation, semistructured interviews were carried out with participants, nurses and practice managers or general practitioners. Due to the nature of the intervention, both participants and nurses were aware of group allocation. RESULTS: We recruited 642 participants ( = 321 for sleep restriction therapy; = 321 for sleep hygiene) between 29 August 2018 and 23 March 2020. Five hundred and eighty participants (90.3%) provided data at a minimum of one follow-up time point; 257 (80.1%) participants in the sleep restriction therapy arm and 291 (90.7%) participants in the sleep hygiene arm provided primary outcome data at 6 months. The estimated adjusted mean difference on the Insomnia Severity Index was -3.05 (95% confidence interval -3.83 to -2.28; < 0.001, Cohen's = -0.74), indicating that participants in the sleep restriction therapy arm [mean (standard deviation) Insomnia Severity Index = 10.9 (5.5)] reported lower insomnia severity compared to sleep hygiene [mean (standard deviation) Insomnia Severity Index = 13.9 (5.2)]. Large treatment effects were also found at 3 ( = -0.95) and 12 months ( = -0.72). Superiority of sleep restriction therapy over sleep hygiene was evident at 3, 6 and 12 months for self-reported sleep, mental health-related quality of life, depressive symptoms, work productivity impairment and sleep-related quality of life. Eight participants in each group experienced serious adverse events but none were judged to be related to the intervention. The incremental cost per quality-adjusted life-year gained was £2075.71, giving a 95.3% probability that the intervention is cost-effective at a cost-effectiveness threshold of £20,000. The process evaluation found that sleep restriction therapy was acceptable to both nurses and patients, and delivered with high fidelity. LIMITATIONS: While we recruited a clinical sample, 97% were of white ethnic background and 50% had a university degree, which may limit generalisability to the insomnia population in England. CONCLUSIONS: Brief nurse-delivered sleep restriction therapy in primary care is clinically effective for insomnia disorder, safe, and likely to be cost-effective. FUTURE WORK: Future work should examine the place of sleep restriction therapy in the insomnia treatment pathway, assess generalisability across diverse primary care patients with insomnia, and consider additional methods to enhance patient engagement with treatment. TRIAL REGISTRATION: This trial is registered as ISRCTN42499563. FUNDING: The award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/84/01) and is published in full in ; Vol. 28, No. 36. See the NIHR Funding and Awards website for further award information.
79Network meta-analysis examining efficacy of components of cognitive behavioural therapy for insomnia.PubMed
Lisa Steinmetz, Laura Simon, Bernd Feige, et al.
Clin Psychol Rev. 2024 Dec;114:102507. doi: 10.1016/j.cpr.2024.102507. Epub 2024 Oct 28.
Cognitive behavioural therapy for insomnia (CBTI) is recommended as first-line treatment for insomnia. CBT-I is a multi-component intervention comprising psychoeducation, sleep restriction, stimulus control, cognitive, and relaxation therapy. The relative efficacy of its components has yet to be investigated with state-of-the-art meta-analytic methods. PubMed, MEDLINE, PsycINFO, PsycARTICLES, and CINAHL were searched according to a pre-registered protocol using search terms indicative of insomnia and CBTI. Baseline-to-post-treatment effect sizes (Cohen's d) were calculated in a component network meta-analysis. Eighty studies representing 15,351 participants (mean age 44.9 years, 70.1 % female) were included. For the primary outcome insomnia severity, a significant positive effect for sleep restriction therapy (d = -0.45; 95 % CI: [-0.63; -0.36]) was found. Overall, the results suggest that sleep restriction therapy improves self-reported sleep continuity and sleep quality, and stimulus control therapy improves self-reported and objective total sleep time. No significant effects of psychoeducation, relaxation therapy, and cognitive therapy, and no further significant effects of any CBT-I component on objective sleep parameters were found. The most common sources of bias were a lack of blinding, missing outcome data, and the absence of study protocols. The current results suggest that sleep restriction therapy and stimulus control therapy are the most effective components of CBT-I.
80Effect of Telephone Cognitive Behavioral Therapy for Insomnia in Older Adults With Osteoarthritis Pain: A Randomized Clinical Trial.PubMed
Susan M McCurry, Weiwei Zhu, Michael Von Korff, et al.
JAMA Intern Med. 2021 Apr 1;181(4):530-538. doi: 10.1001/jamainternmed.2020.9049.
IMPORTANCE: Scalable delivery models of cognitive behavioral therapy for insomnia (CBT-I), an effective treatment, are needed for widespread implementation, particularly in rural and underserved populations lacking ready access to insomnia treatment. OBJECTIVE: To evaluate the effectiveness of telephone CBT-I vs education-only control (EOC) in older adults with moderate to severe osteoarthritis pain. DESIGN, SETTING, AND PARTICIPANTS: This is a randomized clinical trial of 327 participants 60 years and older who were recruited statewide through Kaiser Permanente Washington from September 2016 to December 2018. Participants were double screened 3 weeks apart for moderate to severe insomnia and osteoarthritis (OA) pain symptoms. Blinded assessments were conducted at baseline, after 2 months posttreatment, and at 12-month follow-up. INTERVENTIONS: Six 20- to 30-minute telephone sessions provided over 8 weeks. Participants submitted daily diaries and received group-specific educational materials. The CBT-I instruction included sleep restriction, stimulus control, sleep hygiene, cognitive restructuring, and homework. The EOC group received information about sleep and OA. MAIN OUTCOMES AND MEASURES: The primary outcome was score on the Insomnia Severity Index (ISI) at 2 months posttreatment and 12-month follow-up. Secondary outcomes included pain (score on the Brief Pain Inventory-short form), depression (score on the 8-item Patient Health Questionnaire), and fatigue (score on the Flinders Fatigue Scale). RESULTS: Of the 327 participants, the mean (SD) age was 70.2 (6.8) years, and 244 (74.6%) were women. In the 282 participants with follow-up ISI data, the total 2-month posttreatment ISI scores decreased 8.1 points in the CBT-I group and 4.8 points in the EOC group, an adjusted mean between-group difference of -3.5 points (95% CI, -4.4 to -2.6 points; P < .001). Results were sustained at 12-month follow-up (adjusted mean difference, -3.0 points; 95% CI, -4.1 to -2.0 points; P < .001). At 12-month follow-up, 67 of 119 (56.3%) participants receiving CBT-I remained in remission (ISI score, ≤7) compared with 33 of 128 (25.8%) participants receiving EOC. Fatigue was also significantly reduced in the CBT-I group compared with the EOC group at 2 months posttreatment (mean between-group difference, -2.0 points; 95% CI, -3.1 to -0.9 points; P = <.001) and 12-month follow-up (mean between-group difference, -1.8 points; 95% CI, -3.1 to -0.6 points; P = .003). Posttreatment significant differences were observed for pain, but these differences were not sustained at 12-month follow-up. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, telephone CBT-I was effective in improving sleep, fatigue, and, to a lesser degree, pain among older adults with comorbid insomnia and OA pain in a large statewide health plan. Results support provision of telephone CBT-I as an accessible, individualized, effective, and scalable insomnia treatment. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT02946957.
81A scoping review of self-help cognitive behavioural therapy for insomnia.PubMed
R C Lake, R E Tucker, A L Murphy, et al.
Sleep Med Rev. 2025 Feb;79:102021. doi: 10.1016/j.smrv.2024.102021. Epub 2024 Nov 10.
Uptake of cognitive behavioural therapy for insomnia (CBTI) as first-line therapy of chronic insomnia has been restricted by a shortage of trained therapists, access barriers, and limited awareness of self-help alternatives. Self-help CBTI has emerged as a practical alternative, offering ready access, convenience, and dissemination and scalability efficiency. Yet, evidence syntheses of limited data have suggested its effectiveness and acceptability may be inferior to face-to-face CBTI and others have questioned its fidelity with CBTI standards. We conducted a scoping review to map and characterize self-help CBTI research, focusing on its core components, delivery methods, use of coaching support, and growth. Our review included 174 reports of 145 unique studies, 106 of which were randomized trials, with 65 published since 2020. Findings revealed that self-help CBTI maintained the essential core components (time-in-bed restriction, stimulus control, relaxation techniques, cognitive therapy, and sleep hygiene/education) and structure of conventional CBTI with many, but not all, including different types and formats of coaching support. The expanding body of evidence suggests that self-help CBTI is an evolving field, warranting further analysis to delineate its role in filling the treatment gap for chronic insomnia.
82Innovative Digital Cognitive Behavioral Treatment for Insomnia Disorder in Adults (dCBT-i): Framework Development.PubMed
Emilie Stern, Severine Brune, Stéphane Mouchabac, et al.
JMIR Hum Factors. 2025 May 27;12:e70193. doi: 10.2196/70193.
BACKGROUND: Chronic insomnia, or insomnia disorder, is a major health issue with a prevalence of up to 15%. The recommended first-line treatment is cognitive behavioral therapy for insomnia (CBT-i), which, unfortunately, remains insufficiently accessible. Digitalization has the potential to reduce health care access inequalities by offering more flexible and accessible care options. Digital CBT-i (dCBT-i) has been shown to be as effective as in-person CBT-i, highlighting its potential for broader implementation. OBJECTIVE: This study aimed to develop an evidence-based dCBT-i program grounded in theoretical and clinical knowledge, designed for efficient integration into health care systems, and to establish it as the first prescribed digital treatment in France. METHODS: The program was constructed based on validated CBT-i theory and practice, incorporating the latest scientific data on CBT for insomnia. It was designed as a robust multicomponent therapy, integrating an initial standardized assessment and daily intelligent adaptation to enable digital phenotyping and provide personalized treatment. RESULTS: We developed an innovative digital solution that combines scientific rigor with practical application. The program includes a standardized initial evaluation and dynamic personalization through intelligent algorithms. These features allow for the adaptation of therapy based on patient progress and needs, ensuring individualized care. CONCLUSIONS: The development of this dCBT-i program represents a significant milestone in digital health care, offering a scalable solution to the accessibility challenges of traditional CBT-i. Future steps involve conducting clinical studies to further evaluate its effectiveness and optimize its implementation within health care systems.
83Efficacy of digital cognitive behavioural therapy for insomnia: a meta-analysis of randomised controlled trials.PubMed
Hui Ling Soh, Roger C Ho, Cyrus S Ho, et al.
Sleep Med. 2020 Nov;75:315-325. doi: 10.1016/j.sleep.2020.08.020. Epub 2020 Aug 26.
OBJECTIVES: Although cognitive behavioural therapy for insomnia (CBT-I) has been recommended the initial therapy for insomnia, its clinical usage remains limited due to the lack of therapists. Digital CBT-I (dCBT-I) can potentially circumvent this problem. This meta-analysis aims to evaluate the short-term and long-term efficacy of dCBT-I for adults with insomnia. METHODS: Systematic search of PubMed, EMBASE, PsycINFO, and CENTRAL from inception till 5 March 2020 was conducted. Randomised controlled trials (RCTs) comparing dCBT-I with controls (wait-list/treatment-as-usual/online education) in adults with insomnia were eligible. The primary outcome was insomnia severity index (ISI) at post-intervention, short-term follow-up (ranging 4 weeks to 6 months) and 1-year follow-up. Mean differences were pooled using the random-effects model. RESULTS: 94 articles were assessed full-text independently by two team members and 33 studies were included in this meta-analysis. 4719 and 4645 participants were randomised to dCBT-I and control respectively. dCBT-I significantly reduces ISI at post-intervention with mean difference -5.00 (95% CI -5.68 to -4.33, p < 0.0001) (I = 79%) compared to control. The improvements were sustained at short-term follow-up, -3.99 (95% CI -4.82 to -3.16, p < 0.0001) and 1-year follow-up, -3.48 (95% CI -4.21 to -2.76, p < 0.0001). Compared to dCBT-I, face-to-face CBT-I produced greater improvement in ISI, 3.07 (95% CI 1.18 to 4.95, p = 0.001). However, this was within the non-inferiority interval of 4 points on ISI. CONCLUSION: This meta-analysis provides strong support for the effectiveness of dCBT-I in treating insomnia. dCBT-I has potential to revolutionise the delivery of CBT-I, improving the accessibility and availability of CBT-I content for insomnia patients worldwide.
84Effectiveness of Digital Cognitive Behavioral Therapy for Insomnia in Young People: Preliminary Findings from Systematic Review and Meta-Analysis.PubMed
Hsin-Jung Tsai, Albert C Yang, Jun-Ding Zhu, et al.
J Pers Med. 2022 Mar 16;12(3):481. doi: 10.3390/jpm12030481.
Various forms of cognitive behavioral therapy for insomnia (CBT-i) have been developed to improve its scalability and accessibility for insomnia management in young people, but the efficacy of digitally-delivered cognitive behavioral therapy for insomnia (dCBT-i) remains uncertain. This study systematically reviewed and evaluated the effectiveness of dCBT-i among young individuals with insomnia. We conducted comprehensive searches using four electronic databases (PubMed, Cochrane Library, PsycINFO, and Embase; until October 2021) and examined eligible records. The search strategy comprised the following three main concepts: (1) participants were adolescents or active college students; (2) dCBT-I was employed; (3) standardized tools were used for outcome measurement. Four randomized controlled trials qualified for meta-analysis. A significant improvement in self-reported sleep quality with a medium-to-large effect size after treatment (Hedges's = -0.58~-0.80) was noted. However, a limited effect was detected regarding objective sleep quality improvement (total sleep time and sleep efficiency measured using actigraphy). These preliminary findings from the meta-analysis suggest that dCBT-i is a moderately effective treatment in managing insomnia in younger age groups, and CBT-i delivered through the web or a mobile application is an acceptable approach for promoting sleep health in young people.
85Enhancing sleep and mood in depressed adolescents: A randomized trial on nurse-led digital cognitive behavioral therapy for insomnia.PubMed
Nan Bai, Min Yin
Sleep Med. 2024 Dec;124:627-636. doi: 10.1016/j.sleep.2024.10.030. Epub 2024 Oct 28.
BACKGROUND: Despite the effectiveness of digital cognitive behavior therapy for insomnia (dCBT-I) in treating comorbid insomnia and depression, its accessibility and high dropout rates among adolescents and young adults remain significant limitations. A potential solution could be nurse-led dCBT-I. This study evaluates the feasibility and efficacy of nurse-led dCBT-I in reducing insomnia symptoms and improving mood in adolescents and young adults with depression. AIMS: Our objective was to evaluate the feasibility and effectiveness of a nurse-led dCBT-I in reducing insomnia severity among adolescents and young adults with depression. METHODS: A parallel-group randomized controlled trial involved 40 adolescents and young adults aged 14 to 24 with major depressive disorder and insomnia. They were assigned to receive either a nurse-led 6-week dCBT-I or usual care. The study evaluated outcomes such as insomnia severity, depression severity, and sleep parameters. Measurements were taken at baseline, immediately after the intervention (6 weeks), and during a follow-up at 18 weeks. RESULTS: The intention-to-treat analysis was performed using a generalized linear mixed model (GLMM). Results indicated that, compared to the control group, participants in the intervention group exhibited a significant reduction in insomnia severity at the 18-week follow-up, with a large effect size (Cohen's d = -0.965, p < 0.001). Additionally, the intervention group demonstrated a significant decrease in depression severity both at the end of the intervention (Cohen's d = -0.686, p = 0.001) and at the 18-week follow-up (Cohen's d = -0.508, p = 0.011), indicating a medium effect size. CONCLUSIONS: Nurse-led dCBT-I is an effective treatment for adolescents and young adults with depression and insomnia.
86Digital CBT-I in Comorbid Insomnia and Depression: Clinical Outcomes From a Pragmatic Randomized Controlled Trial.PubMed
Jennifer Schuffelen, Leonie F Maurer, Annika Gieselmann
Depress Anxiety. 2025 May 26;2025:2171041. doi: 10.1155/da/2171041. eCollection 2025.
Depression affects 8.1% of the German population annually, yet many patients remain resistant to conventional treatments. Given that 85% of individuals with depression also experience chronic insomnia, sleep may represent both a contributing and modifiable treatment factor. This study examines whether adding a fully automated digital cognitive behavioral therapy for insomnia (dCBT-I) to care-as-usual (CAU) improves depressive symptoms. Participants with comorbid depression and insomnia were randomized to either the intervention group (dCBT-I) or the waiting group (WLC). The intervention was delivered via a mobile app or web platform, consisting of 10 sequential core modules based on evidence-based CBT-I techniques. Assessments took place at baseline, 12- and 24-weeks post randomization. The primary outcome was the severity of depressive symptoms (Patient Health Questionnaire-9; PHQ-9). Secondary outcomes included insomnia severity, daytime sleepiness, fatigue, well-being and mechanistic effect measures. Linear mixed models were calculated to determine between-group effects. A total of 140 participants (120 women, mean age: = 39.76 ± 11.65 years) were randomized to dCBT-I (=70) or WLC (=70). Large treatment effects at 12- and 24 weeks showed significant reductions in depressive symptoms (-3.34 and -2.83; s <0.001; s = 0.66-0.78) in the dCBT-I group. Treatment effects in favor of dCBT-I were also found for insomnia severity (s = 1.46-1.94) and most secondary outcomes (s = 0.33-1.14). This study demonstrates that digital dCBT-I can be effective not only for individuals with primary insomnia but also for those with depression. These findings align with previous research, highlighting the crucial role of sleep disturbances in depression management. Moreover, the effects remained stable even in the heterogeneous sample investigated in this study, reinforcing the robustness of dCBT-I across diverse patient groups. Thus, dCBT-I emerges as a promising adjunctive treatment. Considering these findings, it is essential to explore the integration of sleep-focused interventions into standard depression treatment. German Clinical Trial Registry identifier: DRKS00030919.
87Sleep physiology, pathophysiology, and sleep hygiene.PubMed
Navya Baranwal, Phoebe K Yu, Noah S Siegel
Prog Cardiovasc Dis. 2023 Mar-Apr;77:59-69. doi: 10.1016/j.pcad.2023.02.005. Epub 2023 Feb 24.
Despite sleep's fundamental role in maintaining and improving physical and mental health, many people get less than the recommended amount of sleep or suffer from sleeping disorders. This review highlights sleep's instrumental biological functions, various sleep problems, and sleep hygiene and lifestyle interventions that can help improve sleep quality. Quality sleep allows for improved cardiovascular health, mental health, cognition, memory consolidation, immunity, reproductive health, and hormone regulation. Sleep disorders, such as insomnia, sleep apnea, and circadian-rhythm-disorders, or disrupted sleep from lifestyle choices, environmental conditions, or other medical issues can lead to significant morbidity and can contribute to or exacerbate medical and psychiatric conditions. The best treatment for long-term sleep improvement is proper sleep hygiene through behavior and sleep habit modification. Recommendations to improve sleep include achieving 7 to 9 h of sleep, maintaining a consistent sleep/wake schedule, a regular bedtime routine, engaging in regular exercise, and adopting a contemplative practice. In addition, avoiding many substances late in the day can help improve sleep. Caffeine, alcohol, heavy meals, and light exposure later in the day are associated with fragmented poor-quality sleep. These sleep hygiene practices can promote better quality and duration of sleep, with corresponding health benefits.
88Sleep hygiene - What do we mean? A bibliographic review.PubMed
Carla De Pasquale, Mary El Kazzi, Kate Sutherland, et al.
Sleep Med Rev. 2024 Jun;75:101930. doi: 10.1016/j.smrv.2024.101930. Epub 2024 Apr 16.
There is no consensus on the definition of sleep hygiene and its components. We examined the definition of sleep hygiene based on its use in published studies. Four databases (Medline, EMBASE, PsycINFO and CINAHL) were searched from inception until December 31, 2021 for the phrase 'sleep hygiene' in the title or abstract. We identified 548 relevant studies in adults: 250 observational and 298 intervention studies. A definition of sleep hygiene was provided in only 44% of studies and converged on three themes: behavioural factors, environmental factors, and an aspect of control. Sleep hygiene components were explicitly defined in up to 70% of observational studies, but in only 35% of intervention studies. The most commonly considered components of sleep hygiene were caffeine (in 51% of studies), alcohol (46%), exercise (46%), sleep timing (45%), light (42%), napping (39%), smoking (38%), noise (37%), temperature (34%), wind-down routine (33%), stress (32%), and stimulus control (32%), although the specific details of each component varied. Lack of consistency in definitions of sleep hygiene and its components may hinder communication between researchers, clinicians, and the public, and likely limits the utility of sleep hygiene as an intervention.
89Sleep quality: An evolutionary concept analysis.PubMed
Kathy L Nelson, Jean E Davis, Cynthia F Corbett
Nurs Forum. 2022 Jan;57(1):144-151. doi: 10.1111/nuf.12659. Epub 2021 Oct 5.
AIM: To clarify the meaning of the concept sleep quality. BACKGROUND: Sleep loss and sleep quality are global health concerns. Poor sleep quality has significant adverse health outcomes. A clarification of the term is necessary to inform patients and healthcare providers, promote consistent theoretical and operational definitions in research, and develop prevention and treatment strategies. DESIGN: Concept analysis. DATA SOURCES: Scientific literature from electronic databases (CINAHL, PsycINFO, PubMED, Web of Science, and JSTOR) and definitions from online dictionaries. REVIEW METHODS: Rodgers' Evolutionary method was applied to guide the concept analysis to identify and determine the attributes, antecedents, and consequences. RESULTS: Sleep quality is defined as an individual's self-satisfaction with all aspects of the sleep experience. Sleep quality has four attributes: sleep efficiency, sleep latency, sleep duration, and wake after sleep onset. Antecedents include physiological (e.g., age, circadian rhythm, body mass index, NREM, REM), psychological (e.g., stress, anxiety, depression), and environmental factors (e.g., room temperature, television/device use), and family/social commitments. Good sleep quality has positive effects such as feeling rested, normal reflexes, and positive relationships. Poor sleep quality consequences include fatigue, irritability, daytime dysfunction, slowed responses, and increased caffeine/alcohol intake. CONCLUSIONS: Sleep quality is essential, and poor sleep quality contributes to disease and poor health outcomes. Given the extensive consequences of poor sleep quality, nurses and clinicians are vital in instructing the importance of good sleep.
90Sleep Quality: A Narrative Review on Nutrition, Stimulants, and Physical Activity as Important Factors.PubMed
Monika Sejbuk, Iwona Mirończuk-Chodakowska, Anna Maria Witkowska
Nutrients. 2022 May 2;14(9):1912. doi: 10.3390/nu14091912.
Sleep is a cyclically occurring, transient, and functional state that is controlled primarily by neurobiological processes. Sleep disorders and insomnia are increasingly being diagnosed at all ages. These are risk factors for depression, mental disorders, coronary heart disease, metabolic syndrome, and/or high blood pressure. A number of factors can negatively affect sleep quality, including the use of stimulants, stress, anxiety, and the use of electronic devices before sleep. A growing body of evidence suggests that nutrition, physical activity, and sleep hygiene can significantly affect the quality of sleep. The aim of this review was to discuss the factors that can affect sleep quality, such as nutrition, stimulants, and physical activity.
91The effect of caffeine on subsequent sleep: A systematic review and meta-analysis.PubMed
Carissa Gardiner, Jonathon Weakley, Louise M Burke, et al.
Sleep Med Rev. 2023 Jun;69:101764. doi: 10.1016/j.smrv.2023.101764. Epub 2023 Feb 6.
The consumption of caffeine in response to insufficient sleep may impair the onset and maintenance of subsequent sleep. This systematic review and meta-analysis investigated the effect of caffeine on the characteristics of night-time sleep, with the intent to identify the time after which caffeine should not be consumed prior to bedtime. A systematic search of the literature was undertaken with 24 studies included in the analysis. Caffeine consumption reduced total sleep time by 45 min and sleep efficiency by 7%, with an increase in sleep onset latency of 9 min and wake after sleep onset of 12 min. Duration (+6.1 min) and proportion (+1.7%) of light sleep (N1) increased with caffeine intake and the duration (-11.4 min) and proportion (-1.4%) of deep sleep (N3 and N4) decreased with caffeine intake. To avoid reductions in total sleep time, coffee (107 mg per 250 mL) should be consumed at least 8.8 h prior to bedtime and a standard serve of pre-workout supplement (217.5 mg) should be consumed at least 13.2 h prior to bedtime. The results of the present study provide evidence-based guidance for the appropriate consumption of caffeine to mitigate the deleterious effects on sleep.
92Coffee, caffeine, and sleep: A systematic review of epidemiological studies and randomized controlled trials.PubMed
Ian Clark, Hans Peter Landolt
Sleep Med Rev. 2017 Feb;31:70-78. doi: 10.1016/j.smrv.2016.01.006. Epub 2016 Jan 30.
Caffeine is the most widely consumed psychoactive substance in the world. It is readily available in coffee and other foods and beverages, and is used to mitigate sleepiness, enhance performance, and treat apnea in premature infants. This review systematically explores evidence from epidemiological studies and randomized controlled trials as to whether coffee and caffeine have deleterious effects on sleep. Caffeine typically prolonged sleep latency, reduced total sleep time and sleep efficiency, and worsened perceived sleep quality. Slow-wave sleep and electroencephalographic (EEG) slow-wave activity were typically reduced, whereas stage-1, wakefulness, and arousals were increased. Dose- and timing-response relationships were established. The sleep of older adults may be more sensitive to caffeine compared to younger adults. Pronounced individual differences are also present in young people, and genetic studies isolated functional polymorphisms of genes implicated in adenosine neurotransmission and metabolism contributing to individual sensitivity to sleep disruption by caffeine. Most studies were conducted in male adults of Western countries, which limits the generalizability of the findings. Given the importance of good sleep for general health and functioning, longitudinal investigations aimed at establishing possible causal relationships among coffee- and caffeine-induced changes in sleep quality and health development are warranted.
93Effects of exercise training on sleep quality and heart rate variability in middle-aged and older adults with poor sleep quality: a randomized controlled trial.PubMed
Tseng-Hau Tseng, Hsi-Chung Chen, Li-Ying Wang, et al.
J Clin Sleep Med. 2020 Sep 15;16(9):1483-1492. doi: 10.5664/jcsm.8560.
STUDY OBJECTIVES: We aimed (1) to investigate the effect of a 12-week exercise training on sleep quality and heart rate variability in middle-aged and older adults with poor sleep quality and (2) to examine the factors associated with the improvements in sleep quality and heart rate variability parameters. METHODS: Forty adults aged ≥ 40 years with poor sleep quality (mean age = 62 years; 82.5% female) participated in this study. They were randomized into the exercise group or control group. Each exercise training program consisted of 40 minutes of supervised aerobic exercise training and 10 minutes of stretching class, 3 times a week for 12 weeks. Outcome measures included both subjective (Pittsburgh Sleep Quality Index) and objective (actigraphy recordings) sleep quality assessments, a cardiopulmonary exercise test, and heart rate variability assessment. RESULTS: The exercise group showed significant improvements in the global score (P = .003), on all subscales of Pittsburgh Sleep Quality Index (P < .05), and in some heart rate variability parameters compared to the control group. Multiple regression analysis indicated that exercise participation was associated with either the sleep quality (β = -0.617, R² = .407; F = 6.226, P < .001) or heart rate monitor high frequency normalized units (β = 0.503, R² = .225; F = 3.200, P = .003) after adjustment for basic characteristics. However, the statistical significance between exercise participation and heart rate monitor high frequency normalized units diminished after controlling for the Pittsburgh Sleep Quality Index. CONCLUSIONS: Our results indicated that moderate-intensity exercise training had a beneficial effect on sleep quality and cardiac autonomic function. Middle-aged and older adults with poor sleep quality should be encouraged to engage in a moderate-intensity aerobic exercise training to improve their sleep quality and cardiac autonomic function. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: The Effects of Exercise Training in Community-dwelling Elderly With Sleep Disturbances With Follow-up; URL: https://clinicaltrials.gov/ct2/show/NCT03005990; Identifier: NCT03005990.
94Aerobic exercise improves self-reported sleep and quality of life in older adults with insomnia.PubMed
Kathryn J Reid, Kelly Glazer Baron, Brandon Lu, et al.
Sleep Med. 2010 Oct;11(9):934-40. doi: 10.1016/j.sleep.2010.04.014. Epub 2010 Sep 1.
OBJECTIVE: To assess the efficacy of moderate aerobic physical activity with sleep hygiene education to improve sleep, mood and quality of life in older adults with chronic insomnia. METHODS: Seventeen sedentary adults aged >or=55 years with insomnia (mean age 61.6 [SD±4.3] years; 16 female) participated in a randomized controlled trial comparing 16 weeks of aerobic physical activity plus sleep hygiene to non-physical activity plus sleep hygiene. Eligibility included primary insomnia for at least 3 months, habitual sleep duration <6.5h and a Pittsburgh Sleep Quality Index (PSQI) score >5. Outcomes included sleep quality, mood and quality of life questionnaires (PSQI, Epworth Sleepiness Scale [ESS], Short-form 36 [SF-36], Center for Epidemiological Studies Depression Scale [CES-D]). RESULTS: The physical activity group improved in sleep quality on the global PSQI (p<.0001), sleep latency (p=.049), sleep duration (p=.04), daytime dysfunction (p=.027), and sleep efficiency (p=.036) PSQI sub-scores compared to the control group. The physical activity group also had reductions in depressive symptoms (p=.044), daytime sleepiness (p=.02) and improvements in vitality (p=.017) compared to baseline scores. CONCLUSION: Aerobic physical activity with sleep hygiene education is an effective treatment approach to improve sleep quality, mood and quality of life in older adults with chronic insomnia.
95Effectiveness of Aerobic Exercise and Tai Chi Interventions on Sleep Quality in Patients With Advanced Lung Cancer: A Randomized Clinical Trial.PubMed
Naomi Takemura, Denise Shuk Ting Cheung, Daniel Yee Tak Fong, et al.
JAMA Oncol. 2024 Feb 1;10(2):176-184. doi: 10.1001/jamaoncol.2023.5248.
IMPORTANCE: Sleep disturbances prevalent among patients with advanced lung cancer can aggravate physical and psychological symptoms, contributing to decreased quality of life and survival. OBJECTIVE: To compare the effectiveness of 2 physical activities of different modalities and intensities, namely aerobic exercise (AE) and tai chi (TC), on subjective sleep quality, physical and psychological outcomes, and survival in patients with advanced lung cancer. DESIGN, SETTING, AND PARTICIPANTS: This assessor-blinded, randomized clinical trial was conducted in 3 public hospitals in Hong Kong between December 19, 2018, and September 7, 2022. A total of 226 patients with advanced lung cancer were recruited and randomized 1:1:1 to AE, TC, or the control group. INTERVENTIONS: For 16 weeks, the AE group received two 60-minute supervised group exercise sessions and home-based exercises per month, and the TC group received 60-minute group sessions twice weekly. The control group received physical activity guidelines. MAIN OUTCOMES AND MEASURES: The primary outcome was subjective sleep quality. Secondary outcomes included objective sleep measures, anxiety, depression, fatigue, quality of life, physical function, circadian rhythm, and 1-year survival. Assessments were conducted at baseline, 16 weeks (T1), and 1 year (T2). RESULTS: The 226 participants had a mean (SD) age of 61.41 (8.73) years, and 122 (54.0%) were female. Compared with the control group, participants in the AE and TC groups showed statistically significant improvements in subjective sleep quality from baseline to T1 (AE: between-group difference, -2.72; 95% CI, -3.97 to -1.46; P < .001; TC: between-group difference, -4.21; 95% CI, -5.48 to -2.94; P < .001) and T2 (AE: between-group difference, -1.75; 95% CI, -3.24 to -0.26; P = .02; TC: between-group difference, -3.95; 95% CI, -5.41 to -2.49; P < .001), psychological distress, physical function, step count, and circadian rhythm. The TC group had a statistically significant greater improvement in sleep than the AE group at T1 (between-group difference, -1.49; 95% CI, -2.77 to -0.22; P = .02) and T2 (between-group difference, -2.20; 95% CI, -3.57 to -0.83; P < .001). Participants in the TC group showed statistically significant improvement in survival compared with the control group. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, AE and TC improved sleep, psychological distress, physical function, and circadian rhythm, with TC demonstrating greater benefits on sleep and survival. Both exercises, but particularly TC, can be incorporated into lung cancer survivorship care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04119778.
96Effect of High-Intensity Interval Training on Quality of Life, Sleep Quality, Exercise Motivation and Enjoyment in Sedentary People with Type 1 Diabetes Mellitus.PubMed
Jesús Alarcón-Gómez, Iván Chulvi-Medrano, Fernando Martin-Rivera, et al.
Int J Environ Res Public Health. 2021 Nov 30;18(23):12612. doi: 10.3390/ijerph182312612.
(1) Background: Type 1 diabetes mellitus (T1DM) people's health-related quality of life (HRQoL) is affected by glycemic control. Regular exercise is strongly recommended to these patients due to its cardiovascular and metabolic benefits. However, a large percentage of patients with T1DM people present a sedentary behavior because of the fear of a post-exercise hypoglycemia event, lack of time, lack of motivation and the complicated management of exercise, glycemic and insulin dose interaction. High-intensity interval training (HIIT) is an efficient and safe methodology since it prevents hypoglycemia and does not require much time, which are the main barriers for this population to doing exercise and increasing physical conditioning. (2) Methods: Nineteen sedentary adults (37 ± 6.5 years) with T1DM, were randomly assigned to 6 weeks of either HIIT (12-16-20 × 30-s intervals interspersed with 1-min rest periods) performed thrice weekly, or to the control group, which did not train. HRQoL, sleep quality, exercise motivation and enjoyment were measured as psychological variables. (4) Results: HRQoL improved in physical and social domains, PF (1.9%); PR (80.3%); GH (16.6); SF (34.1%). Sleep quality improved in the HIIT group by 21.4%. Enjoyment improved by 7% and intrinsic motivation was increased by 13%. (5) Conclusions: We suggest that the 6-week HIIT program used in the present study is safe, since no severe hypoglycemia were reported, and an effective strategy in improving HRQoL, sleep quality, exercise motivation and enjoyment which are important psychological well-being factors in T1DM people.
97Comparative efficacy of exercise regimens on sleep quality in older adults: A systematic review and network meta-analysis.PubMed
Faizul Hasan, Yu-Kang Tu, Chih-Ming Lin, et al.
Sleep Med Rev. 2022 Oct;65:101673. doi: 10.1016/j.smrv.2022.101673. Epub 2022 Aug 27.
The efficacies of various exercise modalities in improving older adults' sleep quality remain unclear. Therefore, in this study, network meta-analysis was performed by comparing the efficacies of various exercise regimens in improving sleep quality in this age group. Six electronic databases were searched for relevant studies between the date of database creation and August 13, 2021. Only randomized controlled trials reporting the effects of exercise on sleep quality in this population were included. Random-effects network meta-analysis based on a frequentist framework was conducted. In total, 35 trials involving 3519 older adults were included. Cognitive behavioral therapy for insomnia, muscle endurance training combined with walking, Tai chi, Baduanjin, resistance training combined with walking, and resistance training significantly improved sleep quality to a greater degree than did usual care (P < 0.05). Muscle endurance training combined with walking led to significantly higher sleep quality than did regimens involving sleep hygiene, Pilates, only walking, health education, resistance training, Taichi, resistance training combined with walking, or yoga. Muscle endurance training combined with walking was identified as the optimal exercise program (88.9%) for enhancing sleep quality in older adults. The results of this study support the claim that exercise can improve sleep quality in this population. PROSPERO registration number: CRD42020178209.
98The effect of mindfulness meditation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.PubMed
Heather L Rusch, Michael Rosario, Lisa M Levison, et al.
Ann N Y Acad Sci. 2019 Jun;1445(1):5-16. doi: 10.1111/nyas.13996. Epub 2018 Dec 21.
There is a growing interest in the effectiveness of mindfulness meditation for sleep disturbed populations. Our study sought to evaluate the effect of mindfulness meditation interventions on sleep quality. To assess for relative efficacy, comparator groups were restricted to specific active controls (such as evidenced-based sleep treatments) and nonspecific active controls (such as time/attention-matched interventions to control for placebo effects), which were analyzed separately. From 3303 total records, 18 trials with 1654 participants were included. We determined the strength of evidence using four domains (risk of bias, directness of outcome measures, consistency of results, and precision of results). At posttreatment and follow-up, there was low strength of evidence that mindfulness meditation interventions had no effect on sleep quality compared with specific active controls (ES 0.03 (95% CI -0.43 to 0.49)) and (ES -0.14 (95% CI -0.62 to 0.34)), respectively. Additionally, there was moderate strength of evidence that mindfulness meditation interventions significantly improved sleep quality compared with nonspecific active controls at postintervention (ES 0.33 (95% CI 0.17-0.48)) and at follow-up (ES 0.54 (95% CI 0.24-0.84)). These preliminary findings suggest that mindfulness meditation may be effective in treating some aspects of sleep disturbance. Further research is warranted.
99Mindfulness-based interventions: an overall review.PubMed
Dexing Zhang, Eric K P Lee, Eva C W Mak, et al.
Br Med Bull. 2021 Jun 10;138(1):41-57. doi: 10.1093/bmb/ldab005.
INTRODUCTION: This is an overall review on mindfulness-based interventions (MBIs). SOURCES OF DATA: We identified studies in PubMed, EMBASE, CINAHL, PsycINFO, AMED, Web of Science and Google Scholar using keywords including 'mindfulness', 'meditation', and 'review', 'meta-analysis' or their variations. AREAS OF AGREEMENT: MBIs are effective for improving many biopsychosocial conditions, including depression, anxiety, stress, insomnia, addiction, psychosis, pain, hypertension, weight control, cancer-related symptoms and prosocial behaviours. It is found to be beneficial in the healthcare settings, in schools and workplace but further research is warranted to look into its efficacy on different problems. MBIs are relatively safe, but ethical aspects should be considered. Mechanisms are suggested in both empirical and neurophysiological findings. Cost-effectiveness is found in treating some health conditions. AREAS OF CONTROVERSY: Inconclusive or only preliminary evidence on the effects of MBIs on PTSD, ADHD, ASD, eating disorders, loneliness and physical symptoms of cardiovascular diseases, diabetes, and respiratory conditions. Furthermore, some beneficial effects are not confirmed in subgroup populations. Cost-effectiveness is yet to confirm for many health conditions and populations. GROWING POINTS: Many mindfulness systematic reviews and meta-analyses indicate low quality of included studies, hence high-quality studies with adequate sample size and longer follow-up period are needed. AREAS TIMELY FOR DEVELOPING RESEARCH: More research is needed on online mindfulness trainings and interventions to improve biopsychosocial health during the COVID-19 pandemic; Deeper understanding of the mechanisms of MBIs integrating both empirical and neurophysiological findings; Long-term compliance and effects of MBIs; and development of mindfulness plus (mindfulness+) or personalized mindfulness programs to elevate the effectiveness for different purposes.
100A randomized controlled trial of mindfulness meditation for chronic insomnia.PubMed
Jason C Ong, Rachel Manber, Zindel Segal, et al.
Sleep. 2014 Sep 1;37(9):1553-63. doi: 10.5665/sleep.4010.
STUDY OBJECTIVES: To evaluate the efficacy of mindfulness meditation for the treatment of chronic insomnia. DESIGN: Three-arm, single-site, randomized controlled trial. SETTING: Academic medical center. PARTICIPANTS: Fifty-four adults with chronic insomnia. INTERVENTIONS: Participants were randomized to either mindfulness-based stress reduction (MBSR), mindfulness-based therapy for insomnia (MBTI), or an eight-week self-monitoring (SM) condition. MEASUREMENTS AND RESULTS: Patient-reported outcome measures were total wake time (TWT) from sleep diaries, the pre-sleep arousal scale (PSAS), measuring a prominent waking correlate of insomnia, and the Insomnia Severity Index (ISI) to determine remission and response as clinical endpoints. Objective sleep measures were derived from laboratory polysomnography and wrist actigraphy. Linear mixed models showed that those receiving a meditation-based intervention (MBSR or MBTI) had significantly greater reductions on TWT minutes (43.75 vs 1.09), PSAS (7.13 vs 0.16), and ISI (4.56 vs 0.06) from baseline-to-post compared to SM. Post hoc analyses revealed that each intervention was superior to SM on each of the patient-reported measures, but no significant differences were found when comparing MBSR to MBTI from baseline-to-post. From baseline to 6-month follow-up, MBTI had greater reductions in ISI scores than MBSR (P < 0.05), with the largest difference occurring at the 3-month follow-up. Remission and response rates in MBTI and MBSR were sustained from post-treatment through follow-up, with MBTI showing the highest rates of treatment remission (50%) and response (78.6%) at the 6-month follow-up. CONCLUSIONS: Mindfulness meditation appears to be a viable treatment option for adults with chronic insomnia and could provide an alternative to traditional treatments for insomnia. TRIAL REGISTRATION: Mindfulness-Based Approaches to Insomnia: clinicaltrials.gov, identifier: NCT00768781.
101Bedtime music therapy for college students with insomnia: A randomized assessor-blinded controlled trial.PubMed
Danni Yan, Yufei Wu, Ruihan Luo, et al.
Sleep Med. 2024 Sep;121:326-335. doi: 10.1016/j.sleep.2024.07.018. Epub 2024 Jul 18.
BACKGROUND: Insomnia, a prevalent sleep disorder in contemporary society, frequently coexists with other mental health conditions such as depression, schizophrenia, and obsessive-compulsive disorder. Sleep disorders can compromise daytime functioning and overall quality of life. While music has been explored as an adjunct therapy for insomnia, its efficacy in improving insomnia among students remains unclear. METHODS: Seventy-five students, aged between 18 and 30 years with an average age of 20.97 years (SD: 1.92), presenting sleep issues were randomly allocated to one of three groups: the classical music group, the jazz music group, and the control group, each with 25 participants. Participants in the classical and jazz music group were instructed to listen to classical or jazz music for a minimum of 30 min preceding bedtime. This was paired with deep breathing and relaxation techniques, practiced two consecutive nights per week from 23:00 to 01:00 over a five-week intervention period. Conversely, participants in the control group were only directed to follow the deep breathing and relaxation techniques before sleep on two consecutive nights weekly. Insomnia severity with the Insomnia Severity Index (ISI), sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), depressive symptoms with the Beck Depression Inventory-II (BDI- II), and anxiety symptoms with the Self-rating Anxiety Scale (SAS). Measurements were taken at baseline, after the second week of intervention, at the intervention's conclusion (five weeks), and two months post-intervention (follow-up). RESULTS: 1. The music groups showed a significant difference in insomnia severity compared with the control group after five weeks of intervention(p < .05). 2. music groups exhibited significant enhancements in sleep quality relative to the control group after a five-week intervention (p < .05). 3. Regarding mood enhancement, music groups showed significant improvements in depression and anxiety symptoms compared to the baseline after the five-week intervention. Notably, the control group also displayed improvements in these symptoms post-intervention. CONCLUSION: 1. Integrating music into a consistent bedtime routine ameliorates sleep quality and insomnia severity. However, no specific genre of music emerged as the superior choice for pre-sleep listening. 2. While music can considerably enhance mood indicators like depression and anxiety, techniques such as deep breathing and mindfulness also contribute positively. 3. Incorporating music before sleep tangibly elevates overall quality of life and daytime functioning. TRIAL REGISTRATION: ChiCTR2300073953.
102Can music improve sleep quality in adults with primary insomnia? A systematic review and network meta-analysis.PubMed
Fan Feng, Yingshi Zhang, Jun Hou, et al.
Int J Nurs Stud. 2018 Jan;77:189-196. doi: 10.1016/j.ijnurstu.2017.10.011. Epub 2017 Oct 23.
BACKGROUND: Primary insomnia is one of the most common issues for adults. However, whether to use music intervention as a non-pharmacological method of treatment, as well as which treatment should be preferred, is still a matter of controversy. Therefore, we aimed to compare and rank music interventions and no-music controls for primary insomnia patients. METHODS: A network meta-analysis was used to identify evidence from relevant clinical trials. We searched PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure Library for publications up to May 2017, pertaining to music intervention for primary insomnia patients. The prespecified primary outcome was sleep quality (scored by the PSQI and overall), and the secondary outcomes were sleep onset latency and sleep efficiency. We did pairwise meta-analyses using the random-effects model, later completing the random-effects network meta-analyses. The study was registered with PROSPERO, number CRD42017064750. RESULTS: We deemed 20 trials to be eligible, involving 1339 patients and 12 intervention arms. For PSQI scores, all intervention arms were statistically more effective than the usual care, with patients ranking listening to music as the best means of intervention (SMD: -0.61, 95%CrI: -1.01 to -0.20). For overall sleep quality, only music-associated relaxation was statistically more effective than the patients' usual care (-0.28, -0.48 to -0.08). In terms of sleep onset latency, music-associated relaxation and listening to music had significant advantages (-0.26, -0.64 to -0.09, and -0.28, -0.53 to -0.02); listening to music and music with exercise displayed a tendency to improve sleep efficiency. CONCLUSIONS: When considering the efficacy, music intervention seemed to offer clear advantages for adults with primary insomnia. Listening to music and music-associated relaxation are probably the best options to consider in the application of music intervention.
103Evidence for music therapy and music medicine in psychiatry: transdiagnostic meta-review of meta-analyses.PubMed
Alexander Lassner, Spyridon Siafis, Emanuel Wiese, et al.
BJPsych Open. 2024 Dec 13;11(1):e4. doi: 10.1192/bjo.2024.826.
BACKGROUND: Music therapy is a commonly used intervention added to usual care for psychiatric disorders. AIMS: We review the evidence for music therapy and assess its efficacy as an adjunct therapy across psychiatric disorders. METHOD: A systematic literature search was conducted in four scientific databases to identify relevant meta-analyses. Articles were assessed with the AMSTAR-2 tool. The results of the high-quality articles were recalculated with the data from the primary studies. We decided to add the results of the lower-rated articles, using a narrative approach. We pooled the primary studies and calculated standardised mean differences (SMD) for the transdiagnostic outcomes of depression, anxiety and quality of life. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool to assess the level of evidence. RESULTS: Meta-analyses were available for autism, dementia, depression, insomnia, schizophrenia and substance use disorders. We identified 40 relevant articles. One article per domain was identified as high quality. Music therapy added to treatment as usual showed therapeutic value in each disorder. The transdiagnostic results showed a positive effect of music therapy on depression (SMD = 0.57, 95% CI 0.36-0.78), anxiety (SMD = 0.47, 95% CI 0.27-0.66) and quality of life (SMD = 0.47, 95% CI 0.24-0.71). However, these effects were not maintained at follow-up, and all results were based on low or very low evidence. CONCLUSIONS: Music therapy shows promising potential as an adjunctive treatment for psychiatric disorders, but methodological weaknesses and variability limit the evidence. More high-quality, well-powered studies are needed to reliably confirm its effect size.
104Acupuncture for primary insomnia: Effectiveness, safety, mechanisms and recommendations for clinical practice.PubMed
Fei-Yi Zhao, Sarah J Spencer, Gerard A Kennedy, et al.
Sleep Med Rev. 2024 Apr;74:101892. doi: 10.1016/j.smrv.2023.101892. Epub 2023 Dec 11.
Primary insomnia (PI) is an increasing concern in modern society. Cognitive-behavioral therapy for insomnia is the first-line recommendation, yet limited availability and cost impede its widespread use. While hypnotics are frequently used, balancing their benefits against the risk of adverse events poses challenges. This review summarizes the clinical and preclinical evidence of acupuncture as a treatment for PI, discussing its potential mechanisms and role in reliving insomnia. Clinical trials show that acupuncture improves subjective sleep quality, fatigue, cognitive impairments, and emotional symptoms with minimal adverse events. It also positively impacts objective sleep processes, including prolonging total sleep time, improving sleep efficiency, reducing sleep onset latency and wake after sleep onset, and enhancing sleep architecture/structure, including increasing N3% and REM%, and decreasing N1%. However, methodological shortcomings in some trials diminish the overall quality of evidence. Animal studies suggest that acupuncture restores circadian rhythms in sleep-deprived rodents and improves their performance in behavioral tests, possibly mediated by various clinical variables and pathways. These may involve neurotransmitters, brain-derived neurotrophic factors, inflammatory cytokines, the hypothalamic-pituitary-adrenal axis, gut microbiota, and other cellular events. While the existing findings support acupuncture as a promising therapeutic strategy for PI, additional high-quality trials are required to validate its benefits.
105Efficacy and safety of acupuncture treatment on primary insomnia: a randomized controlled trial.PubMed
Xuan Yin, Minghui Gou, Jian Xu, et al.
Sleep Med. 2017 Sep;37:193-200. doi: 10.1016/j.sleep.2017.02.012. Epub 2017 Mar 8.
OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of acupuncture treatment for primary insomnia. METHODS: We conducted a single-center, single-blinded, and randomized controlled clinical trial. Seventy-two patients with primary insomnia were randomly assigned into two groups - the acupuncture group, who received acupuncture treatment, and the control group, who received sham acupuncture treatment. The treatment was given three times a week for four weeks. Patients were asked to wear sleep monitors and complete questionnaires every two weeks for a total of eight weeks. The primary outcome was the Insomnia Severity Index (ISI). The secondary outcomes were sleep parameters including sleep efficiency (SE), sleep awakenings (SA) and total sleep time (TST) recorded by the Actigraphy, as well as scores of the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS). RESULTS: Compared with pretreatment baseline, patients in both groups had varying degrees of improvements in their sleep conditions. Paired t-test showed that there was a significant difference in all indicators in the acupuncture group before and after acupuncture treatment. One-way analysis of covariance adjusted for baseline scores indicated that the ISI improved dramatically in the acupuncture group at two weeks post-treatment (F = 11.3, p = 0.001), four weeks post-treatment (F = 33.6, p < 0.001), 2 weeks follow-up (F = 39.4, p < 0.001) and four weeks follow-up (F = 34.1, p < 0.001). Similar significant improvements can also be observed in the SE, TST and SDS scores. Although no differences in SA and SAS were shown between the two groups until the end of the treatment, remarkable decrements in SA and SAS were found in the acupuncture treatment group after the two-week and four-week follow-ups. CONCLUSION: Acupuncture treatment is more effective than sham acupuncture treatment in increasing insomnia patients' sleep quality and improving their psychological health. TRIAL REGISTRATION: Chinese Clinical Trial Registry: Chi CTR-TRC-14004859.
106Effect of Electroacupuncture on Insomnia in Patients With Depression: A Randomized Clinical Trial.PubMed
Xuan Yin, Wei Li, Tingting Liang, et al.
JAMA Netw Open. 2022 Jul 1;5(7):e2220563. doi: 10.1001/jamanetworkopen.2022.20563.
IMPORTANCE: Electroacupuncture (EA) is a widely recognized therapy for depression and sleep disorders in clinical practice, but its efficacy in the treatment of comorbid insomnia and depression remains uncertain. OBJECTIVE: To assess the efficacy and safety of EA as an alternative therapy in improving sleep quality and mental state for patients with insomnia and depression. DESIGN, SETTING, AND PARTICIPANTS: A 32-week patient- and assessor-blinded, randomized, sham-controlled clinical trial (8-week intervention plus 24-week observational follow-up) was conducted from September 1, 2016, to July 30, 2019, at 3 tertiary hospitals in Shanghai, China. Patients were randomized to receive EA treatment and standard care, sham acupuncture (SA) treatment and standard care, or standard care only as control. Patients were 18 to 70 years of age, had insomnia, and met the criteria for depression as classified in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Data were analyzed from May 4 to September 13, 2020. INTERVENTIONS: All patients in the 3 groups were provided with standard care guided by psychiatrists. Patients in the EA and SA groups received real or sham acupuncture treatment, 3 sessions per week for 8 weeks, for a total of 24 sessions. MAIN OUTCOMES AND MEASURES: The primary outcome was change in Pittsburgh Sleep Quality Index (PSQI) from baseline to week 8. Secondary outcomes included PSQI at 12, 20, and 32 weeks of follow-up; sleep parameters recorded in actigraphy; Insomnia Severity Index; 17-item Hamilton Depression Rating Scale score; and Self-rating Anxiety Scale score. RESULTS: Among the 270 patients (194 women [71.9%] and 76 men [28.1%]; mean [SD] age, 50.3 [14.2] years) included in the intention-to-treat analysis, 247 (91.5%) completed all outcome measurements at week 32, and 23 (8.5%) dropped out of the trial. The mean difference in PSQI from baseline to week 8 within the EA group was -6.2 (95% CI, -6.9 to -5.6). At week 8, the difference in PSQI score was -3.6 (95% CI, -4.4 to -2.8; P < .001) between the EA and SA groups and -5.1 (95% CI, -6.0 to -4.2; P < .001) between the EA and control groups. The efficacy of EA in treating insomnia was sustained during the 24-week postintervention follow-up. Significant improvement in the 17-item Hamilton Depression Rating Scale (-10.7 [95% CI, -11.8 to -9.7]), Insomnia Severity Index (-7.6 [95% CI, -8.5 to -6.7]), and Self-rating Anxiety Scale (-2.9 [95% CI, -4.1 to -1.7]) scores and the total sleep time recorded in the actigraphy (29.1 [95% CI, 21.5-36.7] minutes) was observed in the EA group during the 8-week intervention period (P < .001 for all). No between-group differences were found in the frequency of sleep awakenings. No serious adverse events were reported. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of EA treatment for insomnia in patients with depression, quality of sleep improved significantly in the EA group compared with the SA or control group at week 8 and was sustained at week 32. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03122080.
107Acupuncture for cancer-related insomnia: A systematic review and meta-analysis.PubMed
Jialing Zhang, Zhinan Zhang, Shengtao Huang, et al.
Phytomedicine. 2022 Jul 20;102:154160. doi: 10.1016/j.phymed.2022.154160. Epub 2022 May 14.
BACKGROUND: Cancer-related insomnia is a highly prevalent complaint in cancer patients. However, there is no meta-analytic synthesis explored the efficacy of acupuncture for cancer-related insomnia among cancer patients undergoing active cancer treatments. OBJECTIVE: This systematic review and meta-analysis were performed to explore the efficacy and safety of acupuncture for insomnia in people diagnosed with cancer. STUDY DESIGN: Systematic review and meta-analysis of existing randomized controlled trials on acupuncture in the treatment of cancer-related insomnia. METHODS: According to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement, we identified and extracted the trials through November 2021 from ten databases and two trials record platforms (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PUBMED, Web of Science, PsycINFO, Allied and Complementary Medicine, Cumulative Index to Nursing and Allied Health Literature, China National Knowledge Infrastructure, Wanfang Digital Journals, ClinicalTrials, World Health Organization International Clinical Trials Registry Platform). The quality of the trials was assessed using Jadad score and Risk of Bias (2.0). A meta-analysis was synthesized using the random-effects model if the included studies were in high methodological quality. RESULTS: A total of 690 studies were identified, with 22 were included in the review, and 6 of them were included in the quantitative synthesis. Studies were highly heterogeneous in terms of participant characteristics and study methodologies. Most studies recruited patients diagnosed with a specific cancer type, and breast cancer patients were the subgroup most represented. The qualitative review of available evidence suggested a beneficial efficacy of acupuncture on sleep without serious adverse events in several studies (55%). The meta-analysis revealed that acupuncture produced a significant improvement in the total Pittsburgh Sleep Quality Index (PSQI) score relative to the wait-list control among breast cancer patients undergoing active cancer treatments (MD -1.92, 95% CI -3.25 to -0.59, p = 0.005). Similar improvement of real and sham acupuncture on PSQI score change post-intervention was found (MD: -0.68, 95% CI: -2.44 to 1.07, p = 0.44). Manual acupuncture had similar effective rate as compared to estazolam immediately post-intervention (RR: 0.94, 95% CI: 0.87 to 1.01, p = 0.09), and had significantly better effective rate than estazolam at 1-week post-intervention follow-up (RR: 1.25, 95% CI: 1.10 to 1.43, p = 0.0009). All reported acupuncture related adverse events were mild or moderate in severity. CONCLUSION: Acupuncture has great potential to be used to manage cancer-related insomnia for cancer patients or survivors. More studies with rigorous designs and larger sample size are warranted to verify the efficacy and safety of acupuncture for insomnia among people diagnosed with cancer, in particular among those with clinically significant insomnia. REGISTRATION: PROSPERO (ID: CRD42021285844).
108Acupuncture for cancer-related conditions: An overview of systematic reviews.PubMed
Xiao-Wen Zhang, Wen-Bin Hou, Feng-Lan Pu, et al.
Phytomedicine. 2022 Nov;106:154430. doi: 10.1016/j.phymed.2022.154430. Epub 2022 Sep 5.
BACKGROUND: Acupuncture is commonly used for cancer-related conditions worldwide, and evidence is increasing year on year. There is a need to summarize the evidence of acupuncture for cancer-related conditions comprehensively and critically. OBJECTIVE: To evaluate and summarize the systematic reviews (SRs) that assess the effects and safety of acupuncture for cancer-related conditions, and to inform clinical practice and future studies. METHODS: A comprehensive search was conducted on Pubmed, Embase, the Cochrane Library, Web of Science, CNKI, VIP, Sinomed, and Wanfang from their inception to October 16, 2021. SRs of randomized controlled trials (RCTs) on acupuncture for cancer-related conditions were to be included. Two reviewers screened the eligible articles, and four reviewers in pair extracted data and assessed the methodological quality/risk of bias of all included reviews by AMSTAR 2 and ROBIS tools. The overlap of primary studies was measured by calculating corrected covered areas. Data from the included reviews were synthesized with a summary of meta-analysis or narrative description. RESULTS: Fifty-one SRs of RCTs on acupuncture for cancer-related conditions were included and synthesized. The methodological quality of SRs included 1 "high", 5 "low" and 45 "very low" by AMSTAR 2. Sixteen SRs assessed as low risk of bias (31.37%), and 35 SRs had high risk of bias (68.63%) by ROBIS. Acupuncture showed effective on systemic conditions in relation to different cancers, including cancer-related pain (17 SRs, 80 RCTs), fatigue (7 SRs, 18 RCTs), insomnia (4 SRs, 10 RCTs), quality of life (2 SRs, 15 RCTs); conditions in relation to chemo-radiotherapy, including nausea and vomiting (3 SRs, 36 RCTs) and bone marrow suppression (2 SRs, 21 RCTs); and conditions in relation to specific cancers, including breast cancer-related menopause (3 SRs, 6 RCTs), hot flashes (12 SRs, 13 RCTs), arthralgia (5 SRs, 10 RCTs), and nasopharyngeal cancer-related dysphagia (1 SRs, 7 RCTs). Acupuncture appeared to have benefit for patients with lymphoedema (3 SRs, 3 RCTs), gastrointestinal function (5 SRs, 27 RCTs), and xerostomia (4 SRs, 7 RCTs). Limited evidence showed inconsistent results on acupuncture for chemotherapy-induced peripheral neuropathy (3 SRs, 6 RCTs), depression and anxiety (3 SRs, 9 RCTs). Acupuncture was regarded as a safe therapy for cancer patients as no severe adverse events related were reported. CONCLUSION: Evidence from SRs showed that acupuncture is beneficial to cancer survivors with cancer-related pain, fatigue, insomnia, improved quality of life, nausea and vomiting, bone marrow suppression, menopausal symptoms, arthralgia, and dysphagia, and may also be potential for lymphoedema, gastrointestinal function, and xerostomia. For neuropathy, depression and anxiety, acupuncture should be used as an option based on individual conditions. Acupuncture is relatively safe without serious adverse events. More well-designed clinical trials of acupuncture are recommended on cancer-related depression and anxiety, arthralgia, xerostomia, gastrointestinal dysfunction and dysphagia.
109Acupuncture for chemotherapy-associated insomnia in breast cancer patients: an assessor-participant blinded, randomized, sham-controlled trial.PubMed
Jialing Zhang, Zongshi Qin, Tsz Him So, et al.
Breast Cancer Res. 2023 Apr 26;25(1):49. doi: 10.1186/s13058-023-01645-0.
BACKGROUND: Insomnia is a highly prevalent symptom occurred during and post-chemotherapy. Acupuncture may have beneficial effects in the management of chemotherapy-associated insomnia. This study was conducted to determine the efficacy and safety of acupuncture in improving chemotherapy-associated insomnia in breast cancer patients. METHODS: This assessor-participant blinded, randomized, sham-controlled trial was conducted from November 2019 to January 2022 (follow-up completed July 2022). Participants were referred by oncologists from two Hong Kong hospitals. Assessments and interventions were conducted at the outpatient clinic of School of Chinese Medicine, the University of Hong Kong. The 138 breast cancer patients with chemotherapy-associated insomnia were randomly assigned to receive either 15 sessions of active acupuncture regimen by combining needling into body acupoints and acupressure on auricular acupoints or sham acupuncture control (69 each) for 18 weeks, followed by 24 weeks of follow-up. The primary outcome was measured using Insomnia Severity Index (ISI). Secondary outcomes included the Pittsburgh Sleep Quality Index, Actiwatch and sleep diary for sleep parameters, depression and anxiety, fatigue and pain, and quality of life. RESULTS: There were 87.7% (121/138) participants who completed the primary endpoint (week-6). The active acupuncture regimen was not superior to the sham control in reducing ISI score from baseline to 6 weeks (mean difference: - 0.4, 95% CI - 1.8-1.1; P = 0.609), but produced short-term treatment and long-term follow-up better outcomes in improving sleep onset latency, total sleep time, sleep efficiency, anxiety, depression, and quality of life. Participants of the active acupuncture group had a pronouncedly higher cessation rate of sleeping medications than the sham control (56.5% vs. 14.3%, P = 0.011). All treatment-related adverse events were mild. No participants discontinued treatments due to adverse events. CONCLUSION: The active acupuncture regimen could be considered as an effective option for the management of chemotherapy-associated insomnia. It also could serve as a tapering approach to reduce and even replace the use of sleeping medications in breast cancer patients. Trial registration Clinicaltrials.gov : NCT04144309. Registered 30 October 2019.
110Acupuncture for comorbid depression and insomnia in perimenopause: A feasibility patient-assessor-blinded, randomized, and sham-controlled clinical trial.PubMed
Fei-Yi Zhao, Zhen Zheng, Qiang-Qiang Fu, et al.
Front Public Health. 2023 Feb 6;11:1120567. doi: 10.3389/fpubh.2023.1120567. eCollection 2023.
BACKGROUND AND OBJECTIVE: Whilst acupuncture is widely used for treating psychosomatic diseases, there is little high-quality evidence supporting its application in comorbid perimenopausal depression (PMD) and insomnia (PMI) which are common complaints during climacteric. This feasibility, patient-assessor-blinded, randomized, sham-controlled clinical trial addresses this gap by investigating the efficacy and safety of acupuncture on depressed mood and poor sleep in women with comorbid PMD and PMI. METHODS: Seventy eligible participants were randomly assigned to either real-acupuncture (RA) or sham-acupuncture (SA) groups. Either RA or SA treatment were delivered in 17 sessions over 8 weeks. The primary outcomes for mood and sleep were changes on 17-items Hamilton Depression Rating Scale (HAM-D) and Pittsburgh Sleep Quality Index (PSQI) scores, from baseline to 16-week follow-up. Secondary outcome measures involved anxiety symptoms, perimenopausal symptoms, quality of life, participants' experience of and satisfaction with the acupuncture treatment. Blood samples were taken to measure reproductive hormone levels. Intention-To-Treat and Per-Protocol analyses were conducted with linear mixed-effects models. The James' and Bang's blinding indices were used to assess the adequacy of blinding. RESULTS: Sixty-five participants completed all treatment sessions, and 54 and 41 participants completed the eight- and 16-week follow-ups, respectively. At post-treatment and 8-week follow-up, the RA group showed a significantly greater reduction in PSQI scores than the SA group did; although the reduction of HAM-D scores in RA group was significant, the change was not statistically different from that of SA. There were no significant mean differences between baseline and 16-week follow-up in either HAM-D or PSQI in either group. There were no significant between-group differences in serum reproductive hormone levels. All treatments were tolerable and no serious adverse events were reported, and the blinding was successful. CONCLUSION: Acupuncture is safe and can contribute to clinically relevant improvements in comorbid PMD and PMI, with satisfactory short-and medium-term effects. Whether the anti-depressive benefit of acupuncture is specific or non-specific remains to be determined. No evidence was found for any longer-term benefit of acupuncture compared to sham at 16 weeks. Further research is required to elucidate mechanisms underlying the short to medium term effects of acupuncture.
111Transcutaneous Auricular Vagus Nerve Stimulation for Chronic Insomnia Disorder: A Randomized Clinical Trial.PubMed
Shuai Zhang, Yanan Zhao, Zongshi Qin, et al.
JAMA Netw Open. 2024 Dec 2;7(12):e2451217. doi: 10.1001/jamanetworkopen.2024.51217.
IMPORTANCE: Evidence from randomized clinical trials of transcutaneous auricular vagus nerve stimulation (taVNS) for chronic insomnia disorder is lacking. OBJECTIVE: To evaluate the efficacy and safety of taVNS for chronic insomnia compared with the sham taVNS. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted from October 2021 to December 2022 at a single center in Beijing, China. Patients with chronic insomnia disorder with a Pittsburgh Sleep Quality Index (PSQI) of at least 8 were enrolled. Statistical analysis was performed from June to September 2023. INTERVENTIONS: Patients were allocated to the active taVNS group or sham taVNS group with a 1:1 ratio. Both groups received the stimulation for 30 minutes each time, twice a day, 5 consecutive days a week, with an 8-week treatment and a 12-week follow-up. MAIN OUTCOMES AND MEASURES: The primary end point was the mean change from baseline through week 8 in PSQI scores. Minimal clinically important difference was 2.5 points. Secondary outcomes included mental health, sleepiness, and fatigue. Safety was also evaluated. RESULTS: A total of 72 participants were randomized to either active taVNS group (36 participants; mean [SD] age, 45.2 [14.5] years; 27 [75.0%] female) or the sham taVNS group (36 participants; mean [SD] age, 44.6 [13.9] years; 31 [86.1%] female); 68 participants completed the 8-week intervention. The least-square mean changes from baseline to week 8 in PSQI were -8.2 (95% CI, -9.3 to -7.0) points in the taVNS group and -3.9 (95% CI, -5.1 to -2.7) points in the sham group. Both groups experienced statistically significant improvements from before to after the intervention. However, active taVNS showed a clinically meaningful 4.2-point greater reduction (95% CI, -5.9 to -2.6 points; P < .001; Cohen d effect size, 1.2) in PSQI compared with the sham group (minimal clinically important difference = 2.5 points). Secondary outcomes, including mental health and fatigue, showed similar favorable results. The efficacy of taVNS was sustained throughout the 20-week study period. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, taVNS significantly reduced insomnia severity. Clinically meaningful enhancements in PSQI scores were observed compared with sham stimulation, with the benefits of taVNS sustained over a 20-week period. Future multicenter clinical trials with large sample sizes are needed to validate its effectiveness across diverse populations. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2100051319.
112A critical review on clinical evidence of the efficacy of lavender in sleep disorders.PubMed
Jing Luo, Wubian Jiang
Phytother Res. 2022 Jun;36(6):2342-2351. doi: 10.1002/ptr.7448. Epub 2022 Apr 12.
Sleep disorders are one of the most prevalent psychiatric diseases. Insomnia is the most common sleep disorder amongst the general population. It is also one of the most frequent complaints in primary healthcare centers. Lavender is called "the broom of the brain" in different oriental traditional medicines. It is one of the most used plants for patients with sleep disorders. This study reviews what is currently known about the use of lavender for sleep disorders in patients with different diseases, from cancers and end-stage renal disease to neurological-psychiatric diseases (e.g., depression, dementia, and autism), respiratory, cardiac, and metabolic diseases. Additionally, its most used administration route is the inhalation of its essential oil (i.e., aromatherapy) alone or in combination by massage. Some limitations of the reviewed literature were discussed briefly. Overall, this critical review provides promising evidence of the lavender efficacy for sleep disorders in a wide variety of populations and diseases. However, further clinical studies with robust design and longer durations of intervention are necessary for more evidence-based judgment on its effect on sleep problems and to investigate its mechanism of action.
113Insufficient Evidence to Recommend in Managing Depression With or Without Comorbid Insomnia: A Systematic Review With Meta-Analysis and Trial Sequential Analysis.PubMed
Fei-Yi Zhao, Peijie Xu, Gerard A Kennedy, et al.
Neuropsychiatr Dis Treat. 2025 Jan 31;21:167-183. doi: 10.2147/NDT.S499574. eCollection 2025.
AIM: This systematic review with trial sequential analysis (TSA) aims to evaluate the efficacy and safety of Shu Mian Capsule (SMC), a commercial Chinese polyherbal preparation, for managing depression with or without comorbid insomnia. METHODS: Controlled clinical trials assessing SMC against waitlist control, placebo or active controls, or as an adjunct treatment were searched across seven databases. Risk of bias and evidence quality were assessed using Cochrane criteria and GRADE framework, respectively. RESULTS: Fourteen studies were analyzed, involving 1207 participants. Trials comparing SMC with placebo or standard antidepressive treatments were limited. In depressed patients without comorbid insomnia, combining SMC with antidepressants reduced the incidence of antidepressants-induced sleep disorders (from 12.2% to 3.8%) but did not significantly lower Hamilton Rating Scale for Depression (HAM-D) scores compared to antidepressants alone [SMD = -0.09, 95% CI (-0.32, 0.14), = 0.45]. In depressed patients with comorbid insomnia, the combination of SMC and psychotropic drugs significantly reduced HAM-D [SMD = -1.29, 95% CI (-1.96, -0.62), < 0.01] and Pittsburgh Sleep Quality Index scores [SMD = -1.53, 95% CI (-1.95, -1.11), < 0.01], and exhibited a lower incidence of various drug-related adverse effects compared to psychotropic drugs alone. TSA validated the sample size adequacy; nevertheless, the methodological quality of supporting studies varied from very low to low due to substantial bias risk. Additionally, 92.9% of trials lacked follow-ups. CONCLUSION: The effectiveness of SMC as an alternative to conventional antidepressive treatment is unclear. For depressed patients with comorbid insomnia, adding SMC to standard care demonstrates augmented efficacy and improved safety, though the supporting evidence is methodologically limited. Further rigorous trials are warranted to confirm SMC's short-term efficacy and explore its medium- to long-term effects as either an alternative or complementary therapy. Current evidence precludes recommendations for the administration of SMC in depression.
114The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023.PubMed
Dieter Riemann, Colin A Espie, Ellemarije Altena, et al.
J Sleep Res. 2023 Dec;32(6):e14035. doi: 10.1111/jsr.14035.
Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).
115Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery.PubMed
Tobias Atkin, Stefano Comai, Gabriella Gobbi
Pharmacol Rev. 2018 Apr;70(2):197-245. doi: 10.1124/pr.117.014381.
Although the GABAergic benzodiazepines (BZDs) and Z-drugs (zolpidem, zopiclone, and zaleplon) are FDA-approved for insomnia disorders with a strong evidence base, they have many side effects, including cognitive impairment, tolerance, rebound insomnia upon discontinuation, car accidents/falls, abuse, and dependence liability. Consequently, the clinical use of off-label drugs and novel drugs that do not target the GABAergic system is increasing. The purpose of this review is to analyze the neurobiological and clinical evidence of pharmacological treatments of insomnia, excluding the BZDs and Z-drugs. We analyzed the melatonergic agonist drugs, agomelatine, prolonged-release melatonin, ramelteon, and tasimelteon; the dual orexin receptor antagonist suvorexant; the modulators of the subunit of voltage-sensitive calcium channels, gabapentin and pregabalin; the H antagonist, low-dose doxepin; and the histamine and serotonin receptor antagonists, amitriptyline, mirtazapine, trazodone, olanzapine, and quetiapine. The pharmacology and mechanism of action of these treatments and the evidence-base for the use of these drugs in clinical practice is outlined along with novel pipelines. There is evidence to recommend suvorexant and low-dose doxepin for sleep maintenance insomnia; there is also sufficient evidence to recommend ramelteon for sleep onset insomnia. Although there is limited evidence for the use of the quetiapine, trazodone, mirtazapine, amitriptyline, pregabalin, gabapentin, agomelatine, and olanzapine as treatments for insomnia disorder, these drugs may improve sleep while successfully treating comorbid disorders, with a different side effect profile than the BZDs and Z-drugs. The unique mechanism of action of each drug allows for a more personalized and targeted medical management of insomnia.
116Insomnia: Pharmacologic Treatment.PubMed
Becky X Lou, Margarita Oks
Clin Geriatr Med. 2021 Aug;37(3):401-415. doi: 10.1016/j.cger.2021.04.003. Epub 2021 Jun 4.
Insomnia afflicts many geriatric patients worldwide and results in both clinical and economic consequences. Prescribing hypnotics to the elderly is particularly challenging due to multitudes of adverse effects and drug interactions. Although benzodiazepines and "Z" drugs such as zolpidem have been popular in the past, they carry a high risk of adverse effects in the elderly, such as devastating falls and injuries as well as potentially an increase in mortality. Newer classes of hypnotics such as dual orexin receptor antagonists are much better tolerated and can be explored as a potential treatment for insomnia in the elderly.
117Efficacy and tolerability of pharmacological treatments for insomnia in adults: A systematic review and network meta-analysis.PubMed
Jing-Li Yue, Xiang-Wen Chang, Jun-Wei Zheng, et al.
Sleep Med Rev. 2023 Apr;68:101746. doi: 10.1016/j.smrv.2023.101746. Epub 2023 Jan 14.
Insomnia is one of the most common and burdensome disorders in adults. We compared and ranked insomnia medication on the basis of their efficacy and tolerability. We performed a systematic review and network meta-analysis of placebo-controlled or head-to-head randomized controlled trials for primary insomnia in adults comparing 20 drugs. We searched eight databases and seven trial registers from inception to March 1st, 2022. Primary outcomes included sleep latency (SL), awake time after sleep onset (WASO) and discontinuation for adverse events (AED), and secondary outcomes included total sleep time (TST), sleep efficiency (SE), sleep quality (SQ) and adverse events (ADE). Pooled standardized mean differences or odds ratios with 95% credible intervals were estimated using pairwise and network meta-analysis with random-effects. Differences among trial findings were explored in subgroup and sensitivity analyses. Confidence in evidence was assessed using GRADE. The PROSPERO registered number is CRD42020182144. We identified 22,538 records and included 69 studies (17,319 patients). Orexin receptor antagonists (ORAs) are more efficacious than benzodiazepine-like drugs (Z-drugs) and placebo for WASO and SE, and better than melatonin receptor agonists (MRAs) for SL, WASO and SE. ORAs ranked the best in SL (SUCRA value: 0.84), WASO (0.93), TST (0.86) and SE (0.96). Lemborexant and daridorexant (two ORAs) showed greater efficacy than placebo for SL, WASO, and TST, with good tolerability. Z-drugs were more efficacious than placebo for SL, WASO, TST and SE, but with higher risk to safety. Zaleplon and eszopiclone had better efficacy than placebo for TST and SQ respectively. MRAs may also be efficacious for sleep-onset insomnia with good safety. However, the long-term adverse effects of all medications are unclear. Insomnia medications differ in their efficacy and tolerability. ORAs have superior efficacy and tolerability. These findings should aid clinicians in matching risk/benefits of drugs available in their countries to insomnia symptoms.
118Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis.PubMed
Franco De Crescenzo, Gian Loreto D'Alò, Edoardo G Ostinelli, et al.
Lancet. 2022 Jul 16;400(10347):170-184. doi: 10.1016/S0140-6736(22)00878-9.
BACKGROUND: Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently used worldwide. We aimed to estimate the comparative effectiveness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder. METHODS: In this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, PsycINFO, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and websites of regulatory agencies from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials. We included studies comparing pharmacological treatments or placebo as monotherapy for the treatment of adults (≥18 year) with insomnia disorder. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework. Primary outcomes were efficacy (ie, quality of sleep measured by any self-rated scale), treatment discontinuation for any reason and due to side-effects specifically, and safety (ie, number of patients with at least one adverse event) both for acute and long-term treatment. We estimated summary standardised mean differences (SMDs) and odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with Open Science Framework, https://doi.org/10.17605/OSF.IO/PU4QJ. FINDINGS: We included 170 trials (36 interventions and 47 950 participants) in the systematic review and 154 double-blind, randomised controlled trials (30 interventions and 44 089 participants) were eligible for the network meta-analysis. In terms of acute treatment, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more efficacious than placebo (SMD range: 0·36-0·83 [CINeMA estimates of certainty: high to moderate]). Benzodiazepines, eszopiclone, zolpidem, and zopiclone were more efficacious than melatonin, ramelteon, and zaleplon (SMD 0·27-0·71 [moderate to very low]). Intermediate-acting benzodiazepines, long-acting benzodiazepines, and eszopiclone had fewer discontinuations due to any cause than ramelteon (OR 0·72 [95% CI 0·52-0·99; moderate], 0·70 [0·51-0·95; moderate] and 0·71 [0·52-0·98; moderate], respectively). Zopiclone and zolpidem caused more dropouts due to adverse events than did placebo (zopiclone: OR 2·00 [95% CI 1·28-3·13; very low]; zolpidem: 1·79 [1·25-2·50; moderate]); and zopiclone caused more dropouts than did eszopiclone (OR 1·82 [95% CI 1·01-3·33; low]), daridorexant (3·45 [1·41-8·33; low), and suvorexant (3·13 [1·47-6·67; low]). For the number of individuals with side-effects at study endpoint, benzodiazepines, eszopiclone, zolpidem, and zopiclone were worse than placebo, doxepin, seltorexant, and zaleplon (OR range 1·27-2·78 [high to very low]). For long-term treatment, eszopiclone and lemborexant were more effective than placebo (eszopiclone: SMD 0·63 [95% CI 0·36-0·90; very low]; lemborexant: 0·41 [0·04-0·78; very low]) and eszopiclone was more effective than ramelteon (0.63 [0·16-1·10; very low]) and zolpidem (0·60 [0·00-1·20; very low]). Compared with ramelteon, eszopiclone and zolpidem had a lower rate of all-cause discontinuations (eszopiclone: OR 0·43 [95% CI 0·20-0·93; very low]; zolpidem: 0·43 [0·19-0·95; very low]); however, zolpidem was associated with a higher number of dropouts due to side-effects than placebo (OR 2·00 [95% CI 1·11-3·70; very low]). INTERPRETATION: Overall, eszopiclone and lemborexant had a favorable profile, but eszopiclone might cause substantial adverse events and safety data on lemborexant were inconclusive. Doxepin, seltorexant, and zaleplon were well tolerated, but data on efficacy and other important outcomes were scarce and do not allow firm conclusions. Many licensed drugs (including benzodiazepines, daridorexant, suvorexant, and trazodone) can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available. Melatonin, ramelteon, and non-licensed drugs did not show overall material benefits. These results should serve evidence-based clinical practice. FUNDING: UK National Institute for Health Research Oxford Health Biomedical Research Centre.
119Insomnia disorder.PubMed
Luigi Ferini-Strambi
Minerva Med. 2025 Aug;116(4):309-322. doi: 10.23736/S0026-4806.25.09690-9. Epub 2025 Feb 11.
Insomnia is a prevalent public health issue, characterized by dissatisfaction with the duration, continuity, and quality of sleep. It is closely associated with daytime symptoms, which are essential for diagnosing insomnia disorder. The condition is more common among women, middle-aged and older adults, and individuals with coexisting mental or physical health conditions. Evidence suggests that insomnia increases the risk of various health problems. Addressing insomnia is therefore crucial not only to enhance patients' quality of life but also to mitigate its significant health, social, and economic impacts. However, further studies are needed to evaluate the cost-effectiveness of insomnia treatments. Cognitive behavioral therapy for insomnia (CBT-I) is recommended as the first-line treatment for chronic insomnia in adults. When CBT-I proves ineffective or is unavailable, pharmacological treatments may be considered. Benzodiazepines (BZs) and benzodiazepine receptor agonists (BZRAs) are suitable for short-term treatment (up to 4 weeks). Among BZs, triazolam is notable for its short half-life and demonstrated efficacy in treating sleep-onset and middle-of-the-night (MOTN) insomnia, supported by robust clinical evidence. Additionally, triazolam does not impair psychomotor performance. In certain cases, longer-term use of BZs or BZRAs may be appropriate; however, this approach requires careful individual assessment of the benefits and risks. Non-nightly use of hypnotic medications may also be a viable option for patients who do not require nightly treatment. Low-dose sedating antidepressants may be considered for short-term insomnia management (off-label), while antipsychotics and antihistamines are not recommended for this purpose. Orexin receptor antagonists are an option for treating insomnia for up to three months. It is important to note that although insomnia guidelines are based on daily use as evaluated in randomized controlled trials, clinical practice may vary.
120Antidepressants for insomnia in adults.PubMed
Hazel Everitt, David S Baldwin, Beth Stuart, et al.
Cochrane Database Syst Rev. 2018 May 14;5(5):CD010753. doi: 10.1002/14651858.CD010753.pub2.
BACKGROUND: Insomnia disorder is a subjective condition of unsatisfactory sleep (e.g. sleep onset, maintenance, early waking, impairment of daytime functioning). Insomnia disorder impairs quality of life and is associated with an increased risk of physical and mental health problems including anxiety, depression, drug and alcohol abuse, and increased health service use. hypnotic medications (e.g. benzodiazepines and 'Z' drugs) are licensed for sleep promotion, but can induce tolerance and dependence, although many people remain on long-term treatment. Antidepressant use for insomnia is widespread, but none is licensed for insomnia and the evidence for their efficacy is unclear. This use of unlicensed medications may be driven by concern over longer-term use of hypnotics and the limited availability of psychological treatments. OBJECTIVES: To assess the effectiveness, safety and tolerability of antidepressants for insomnia in adults. SEARCH METHODS: This review incorporated the results of searches to July 2015 conducted on electronic bibliographic databases: the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 6), MEDLINE (1950 to 2015), Embase (1980 to 2015) and PsycINFO (1806 to 2015). We updated the searches to December 2017, but these results have not yet been incorporated into the review. SELECTION CRITERIA: Randomised controlled trials (RCTs) of adults (aged 18 years or older) with a primary diagnosis of insomnia and all participant types including people with comorbidities. Any antidepressant as monotherapy at any dose whether compared with placebo, other medications for insomnia (e.g. benzodiazepines and 'Z' drugs), a different antidepressant, waiting list control or treatment as usual. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility and extracted data using a data extraction form. A third review author resolved disagreements on inclusion or data extraction. MAIN RESULTS: The search identified 23 RCTs (2806 participants).Selective serotonin reuptake inhibitors (SSRIs) compared with placebo: three studies (135 participants) compared SSRIs with placebo. Combining results was not possible. Two paroxetine studies showed significant improvements in subjective sleep measures at six (60 participants, P = 0.03) and 12 weeks (27 participants, P < 0.001). There was no difference in the fluoxetine study (low quality evidence).There were either no adverse events or they were not reported (very low quality evidence).Tricyclic antidepressants (TCA) compared with placebo: six studies (812 participants) compared TCA with placebo; five used doxepin and one used trimipramine. We found no studies of amitriptyline. Four studies (518 participants) could be pooled, showing a moderate improvement in subjective sleep quality over placebo (standardised mean difference (SMD) -0.39, 95% confidence interval (CI) -0.56 to -0.21) (moderate quality evidence). Moderate quality evidence suggested that TCAs possibly improved sleep efficiency (mean difference (MD) 6.29 percentage points, 95% CI 3.17 to 9.41; 4 studies; 510 participants) and increased sleep time (MD 22.88 minutes, 95% CI 13.17 to 32.59; 4 studies; 510 participants). There may have been little or no impact on sleep latency (MD -4.27 minutes, 95% CI -9.01 to 0.48; 4 studies; 510 participants).There may have been little or no difference in adverse events between TCAs and placebo (risk ratio (RR) 1.02, 95% CI 0.86 to 1.21; 6 studies; 812 participants) (low quality evidence).'Other' antidepressants with placebo: eight studies compared other antidepressants with placebo (one used mianserin and seven used trazodone). Three studies (370 participants) of trazodone could be pooled, indicating a moderate improvement in subjective sleep outcomes over placebo (SMD -0.34, 95% CI -0.66 to -0.02). Two studies of trazodone measured polysomnography and found little or no difference in sleep efficiency (MD 1.38 percentage points, 95% CI -2.87 to 5.63; 169 participants) (low quality evidence).There was low quality evidence from two studies of more adverse effects with trazodone than placebo (i.e. morning grogginess, increased dry mouth and thirst). AUTHORS' CONCLUSIONS: We identified relatively few, mostly small studies with short-term follow-up and design limitations. The effects of SSRIs compared with placebo are uncertain with too few studies to draw clear conclusions. There may be a small improvement in sleep quality with short-term use of low-dose doxepin and trazodone compared with placebo. The tolerability and safety of antidepressants for insomnia is uncertain due to limited reporting of adverse events. There was no evidence for amitriptyline (despite common use in clinical practice) or for long-term antidepressant use for insomnia. High-quality trials of antidepressants for insomnia are needed.
121Review of Safety and Efficacy of Sleep Medicines in Older Adults.PubMed
Jennifer L Schroeck, James Ford, Erin L Conway, et al.
Clin Ther. 2016 Nov;38(11):2340-2372. doi: 10.1016/j.clinthera.2016.09.010. Epub 2016 Oct 15.
PURPOSE: Insomnia is problematic for older adults. After behavioral modifications fail to show adequate response, pharmacologic options are used. The pharmacokinetics of agents used to treat insomnia may be altered. This review focuses on the safety and efficacy of medications used to treat insomnia. METHODS: A literature search of Medline, PubMed, and Embase was conducted (January 1966-June 2016). It included systematic reviews, randomized controlled trials, observational studies, and case series that had an emphasis on insomnia in an older population. Search terms included medications approved by the US Food and Drug Administration for insomnia: benzodiazepines (triazolam, estazolam, temazepam, flurazepam, and quazepam), nonbenzodiazepine receptor agonists (non-BzRAs; zaleplon, zolpidem, and eszopiclone), suvorexant, ramelteon, doxepin and trazodone. Off-label drugs such as other antidepressants, antihistamines, antipsychotics, gabapentin, pramipexole, tiagabine, valerian, and melatonin were also included. FINDINGS: Cognitive behavioral therapy and sleep hygiene are considered initial therapy for insomnia. Benzodiazepines are discouraged in the geriatric population, especially for long-term use. Although non-BzRAs have improved safety profiles compared with benzodiazepines, their side effects include dementia, serious injury, and fractures, which should limit their use. Ramelteon has a minimal adverse effect profile and is effective for sleep-onset latency and increased total sleep time, making it a valuable first-line option. Although the data on suvorexant are limited, this drug improves sleep maintenance and has mild adverse effects, including somnolence; residual daytime sedation has been reported, however. Sedating low-dose antidepressants should only be used for insomnia when the patient has comorbid depression. Antipsychotic agents, pramipexole, and tiagabine have all been used for insomnia, but none has been extensively studied in an older population, and all have considerable adverse effects. Gabapentin may be useful in patients with restless leg syndrome or chronic neuropathic pain and insomnia. Diphenhydramine should be avoided in the elderly. Valerian and melatonin are unregulated products that have a small impact on sleep latency and can produce residual sedation. IMPLICATIONS: An ideal treatment for insomnia should help to improve sleep latency and sleep duration with limited awakenings and be without significant adverse effects such as daytime somnolence or decreased alertness. Cognitive behavioral therapy should always be first line treatment. Clinical inertia regarding previous prominent use of benzodiazepines and non-BzRAs will be a significant challenge for patients accustomed to their issuance. The future direction of insomnia treatment should have an emphasis on nonpharmacologic interventions, treating comorbid conditions, and focusing therapy on using benzodiazepines and non-BzRAs as last resorts.
122Melatonin receptor agonists: new options for insomnia and depression treatment.PubMed
Gilberto Spadoni, Annalida Bedini, Silvia Rivara, et al.
CNS Neurosci Ther. 2011 Dec;17(6):733-41. doi: 10.1111/j.1755-5949.2010.00197.x.
The circadian nature of melatonin (MLT) secretion, coupled with the localization of MLT receptors to the suprachiasmatic nucleus, has led to numerous studies of the role of MLT in modulation of the sleep-wake cycle and circadian rhythms in humans. Although much more needs to be understood about the various functions exerted by MLT and its mechanisms of action, three therapeutic agents (ramelteon, prolonged-release MLT, and agomelatine) are already in use, and MLT receptor agonists are now appearing as new promising treatment options for sleep and circadian-rhythm related disorders. In this review, emphasis has been placed on medicinal chemistry strategies leading to MLT receptor agonists, and on the evidence supporting therapeutic efficacy of compounds undergoing clinical evaluation. A wide range of clinical trials demonstrated that ramelteon, prolonged-release MLT and tasimelteon have sleep-promoting effects, providing an important treatment option for insomnia and transient insomnia, even if the improvements of sleep maintenance appear moderate. Well-documented effects of agomelatine suggest that this MLT agonist offers an attractive alternative for the treatment of depression, combining efficacy with a favorable side effect profile. Despite a large number of high affinity nonselective MLT receptor agonists, only limited data on MT₁ or MT₂ subtype-selective compounds are available up to now. Administration of the MT₂-selective agonist IIK7 to rats has proved to decrease NREM sleep onset latency, suggesting that MT₂ receptor subtype is involved in the acute sleep-promoting action of MLT; rigorous clinical studies are needed to demonstrate this hypothesis. Further clinical candidates based on selective activation of MT₁ or MT₂ receptors are expected in coming years.
123Therapeutic effects of melatonin receptor agonists on sleep and comorbid disorders.PubMed
Moshe Laudon, Anat Frydman-Marom
Int J Mol Sci. 2014 Sep 9;15(9):15924-50. doi: 10.3390/ijms150915924.
Several melatonin receptors agonists (ramelteon, prolonged-release melatonin, agomelatine and tasimelteon) have recently become available for the treatment of insomnia, depression and circadian rhythms sleep-wake disorders. The efficacy and safety profiles of these compounds in the treatment of the indicated disorders are reviewed. Accumulating evidence indicates that sleep-wake disorders and co-existing medical conditions are mutually exacerbating. This understanding has now been incorporated into the new Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). Therefore, when evaluating the risk/benefit ratio of sleep drugs, it is pertinent to also evaluate their effects on wake and comorbid condition. Beneficial effects of melatonin receptor agonists on comorbid neurological, psychiatric, cardiovascular and metabolic symptomatology beyond sleep regulation are also described. The review underlines the beneficial value of enhancing physiological sleep in comorbid conditions.
124The efficacy of melatonin and melatonin agonists in insomnia - An umbrella review.PubMed
Tian Ling Low, Faith Nadine Choo, Shian Ming Tan
J Psychiatr Res. 2020 Feb;121:10-23. doi: 10.1016/j.jpsychires.2019.10.022. Epub 2019 Nov 2.
We conducted an umbrella review to summarize all available systematic reviews and meta-analyses investigating the efficacy of melatonin and melatonin agonists in primary and comorbid insomnia disorders. Two independent reviewers conducted a search of Pubmed, EMBASE, Cochrane Database of Systematic Reviews, Google Scholar, PROSPERO and grey literature from inception to July 2018. Methodological quality was assessed using the revised Assessment of Multiple Systematic Reviews Instrument. Eighteen studies were found, with methodological quality ranging from Moderate to Critically Low. Of the twelve papers evaluating melatonin, there is statistically significant improvement in sleep latency and total sleep time, with a lack of consensus on whether these are clinically meaningful. Similar results are observed across the three reviews on ramelteon. The evidence for other melatonin agonists is sparse. We conclude that existing evidence is limited by disparate methodological quality of the papers, as well as a lack of consensus regarding the type, definition and interpretation of outcome measures in the evaluation of efficacy for insomnia.
125Insomnia and menopause: a narrative review on mechanisms and treatments.PubMed
P Proserpio, S Marra, C Campana, et al.
Climacteric. 2020 Dec;23(6):539-549. doi: 10.1080/13697137.2020.1799973. Epub 2020 Sep 3.
The menopausal transition is associated with an increased frequency of sleep disturbances. Insomnia represents one of the most reported symptoms by menopausal women. According to its pathogenetic model (3-P Model), different predisposing factors (i.e. a persistent condition of past insomnia and aging per se) increase the risk of insomnia during menopause. Moreover, multiple precipitating and perpetuating factors should favor its occurrence across menopause, including hormonal changes, menopausal transition stage symptoms (i.e. hot flashes, night sweats), mood disorders, poor health and pain, other sleep disorders and circadian modifications. Thus, insomnia management implies a careful evaluation of the psychological and somatic symptoms of the individual menopausal woman by a multidisciplinary team. Therapeutic strategies encompass different drugs but also behavioral interventions. Indeed, cognitive behavioral therapy represents the first-line treatment of insomnia in the general population, regardless of the presence of mood disorders and/or vasomotor symptoms (VMS). Different antidepressants seem to improve sleep disturbances. However, when VMS are present, menopausal hormone therapy should be considered in the treatment of related insomnia taking into account the risk-benefit profile. Finally, given its good tolerability, safety, and efficacy on multiple sleep and daytime parameters, prolonged-released melatonin should represent a first-line drug in women aged ≥ 55 years.
126Insomnia in older adults: A review of treatment options.PubMed
Roberto León-Barriera, Margaret M Chaplin, Jasleen Kaur, et al.
Cleve Clin J Med. 2025 Jan 2;92(1):43-50. doi: 10.3949/ccjm.92a.24073.
Insomnia is a common and challenging complaint in older adults (> 65 years) because of age-related alterations in sleep physiology. Cognitive behavioral therapy for insomnia is the gold standard for treatment of insomnia in young as well as older patients. Both clinicians and patients often prefer the simplicity of medication, but risks associated with some hypnotics increase with age. Pharmacologic options for older adults include low-dose doxepin, melatonin, ramelteon, and the dual orexin receptor antagonists. A well-informed clinician can help patients navigate the risks and benefits of both pharmacologic and behavioral options.
127Pharmacokinetic and pharmacodynamic evaluation of ramelteon : an insomnia therapy.PubMed
Gilberto Spadoni, Annalida Bedini, Simone Lucarini, et al.
Expert Opin Drug Metab Toxicol. 2015 Jul;11(7):1145-56. doi: 10.1517/17425255.2015.1045487. Epub 2015 May 8.
INTRODUCTION: Ramelteon , a selective melatonin receptor agonist, is the first member of a novel class of hypnotics. It is approved for the treatment of insomnia characterized by sleep onset difficulties in the US and Japan, but not in Europe. AREAS COVERED: The main clinical properties as well as safety issues of ramelteon are described. Relevant publications reporting ramelteon characteristics and its use in insomnia disorder were identified using PubMed and SciFinder databases up to January 2015. Additional information was collected from the US clinical trials database and from Takeda website. EXPERT OPINION: Despite its high prevalence and economic burden, insomnia disorder remains mostly untreated. Ramelteon has demonstrated sleep-promoting effects in clinical trials and clinical practice, and it is not associated with the adverse effects typical of other class of hypnotics. Its efficacy appears to be relatively modest compared to current insomnia therapeutics, and its use seems restricted to patients with sleep onset difficulties. Assessment of ramelteon effects on sleep quality and maintenance, daytime function and of improvements in comorbid insomnia conditions deserves further studies. The potential application of ramelteon in other pathological conditions could open the way to novel therapeutic approaches as well as to new market opportunities.
128Current Insights into the Risks of Using Melatonin as a Treatment for Sleep Disorders in Older Adults.PubMed
Colin Tuft, Elie Matar, Zoe Menczel Schrire, et al.
Clin Interv Aging. 2023 Jan 12;18:49-59. doi: 10.2147/CIA.S361519. eCollection 2023.
Exogenous melatonin is commonly used for sleep disorders in older adults, and its use is increasing over time. It appears to have modest efficacy in treating insomnia and circadian rhythm sleep-wake disorders. Melatonin is commonly perceived to be a safe alternative to other hypnotics and is available without prescription in some jurisdictions. New evidence suggests that endogenous melatonin has pleomorphic effects on multiple organ systems, many of which are poorly understood. This narrative review summarizes the current evidence regarding the safety of melatonin in older adults (defined by age over 65 years). Melatonin appears to have a favorable safety profile in this population, however there is a dearth of evidence regarding the safety of prolonged use. There are several factors which increase the risk of adverse effects of melatonin in older adults, and these should be taken into consideration when prescribing to this population.
129Correlates of (inappropriate) benzodiazepine use: the Netherlands Study of Depression and Anxiety (NESDA).PubMed
Leonie Manthey, Tineke van Veen, Erik J Giltay, et al.
Br J Clin Pharmacol. 2011 Feb;71(2):263-72. doi: 10.1111/j.1365-2125.2010.03818.x.
AIM: Results on determinants of benzodiazepine (BZD) use in general and inappropriate use were inconsistent and mostly univariate. The relative importance of sociodemographic, psychological and physical determinants has never been investigated in a comprehensive, multivariate model. METHODS: We included 429 BZD users and 2423 non-users from the Netherlands Study of Depression and Anxiety (NESDA) in order to investigate sociodemographic, psychological and physical determinants of BZD use and inappropriate use by logistic and linear regression analyses. RESULTS: BZDs were used by a considerable proportion of the 2852 NESDA participants (15.0%). BZD use was independently associated with older age, singleness, unemployment, treatment in secondary care, higher medical consumption (more severe) anxiety, depression (OR [95% CI]=1.95 [1.29, 2.93]), comorbidity, insomnia, SSRI (OR [95% CI]=2.05 [1.55, 2.70]), TCA and other antidepressant (OR [95% CI]=2.44 [1.64, 3.62]) use. Overall, BZD use was rarely in accordance with all guidelines, mainly because most users (82.5%) exceeded the recommended duration of safe use. Inappropriate use was independently associated with older age (β=0.130) and chronic illnesses (β=0.120). Higher scores on agreeableness were associated with less inappropriate use. CONCLUSIONS: Mentally or physically vulnerable subjects were most likely to use BZDs. The most vulnerable (i.e. the old and physically ill) BZD users were at highest risk of inappropriate BZD use. Without further evidence of the effectiveness of BZDs in long-term use, caution in initiating BZD prescriptions is recommended, particularly when patients are chronically ill and old, as those are most likely to display inappropriate use.
130Benzodiazepine Use in Older Adults: Dangers, Management, and Alternative Therapies.PubMed
Matej Markota, Teresa A Rummans, John Michael Bostwick, et al.
Mayo Clin Proc. 2016 Nov;91(11):1632-1639. doi: 10.1016/j.mayocp.2016.07.024.
Several major medical and psychiatric organizations, including the American Geriatrics Society, advise against using benzodiazepines or nonbenzodiazepine hypnotics in older adults. Despite these recommendations, benzodiazepines continue to be massively prescribed to a group with the highest risk of serious adverse effects from these medications. This article summarizes legitimate reasons for prescribing benzodiazepines in the elderly, serious associated risks of prescribing them, particularly when not indicated, barriers physicians encounter in changing their prescription patterns, and evidence-based strategies on how to discontinue benzodiazepines in older patients. Although more research is needed, we propose several alternatives for treating insomnia and anxiety in older adults in primary care settings. These include nonpharmacological approaches such as sleep restriction-sleep compression therapy and cognitive behavioral therapy for anxiety or insomnia, and as well as alternative pharmacological agents.
131Insomnia Management: A Review and Update.PubMed
David P Shaha
J Fam Pract. 2023 Jul;72(6 Suppl):S31-S36. doi: 10.12788/jfp.0620.
Insomnia is a distinct disorder that is common, yet underrecognized and undertreated in primary care. Treating insomnia has been shown to improve outcomes, including reduced risk of developing cardiovascular and mental health disorders. Insomnia is influenced by the brain's regulation of sleep and wake, which are mutually exclusive events. Insomnia should be treated as a distinct condition, even when occurring with a comorbid diagnosis such as depression or anxiety. Clinicians should implement a multimodal approach to insomnia management, including nonpharmacologic interventions and pharmacologic therapy (when indicated). Pharmacologic agents that are approved by the US Food and Drug Administration for insomnia include benzodiazepine receptor agonists (zolpidem, eszopiclone, and zaleplon), low-dose doxepin (tricyclic antidepressant), ramelteon (melatonin receptor agonist), and dual orexin receptor agonists (DORAs, daridorexant, lemborexant, and suvorexant). Unlike other pharmacologic agents, DORAs inhibit wakefulness rather than induce sedation. Additionally, these medications have no evidence of rebound insomnia or withdrawal, and little to no abuse potential. Daridorexant is the newest DORA, has an ideal half-life of 8 hours, and has demonstrated continued efficacy over a 12-month period. Selection of pharmacologic agent should be based on the patient's comorbid conditions, treatment goals and preferences, and other clinical characteristics.
132Comparison of Lemborexant With Placebo and Zolpidem Tartrate Extended Release for the Treatment of Older Adults With Insomnia Disorder: A Phase 3 Randomized Clinical Trial.PubMed
Russell Rosenberg, Patricia Murphy, Gary Zammit, et al.
JAMA Netw Open. 2019 Dec 2;2(12):e1918254. doi: 10.1001/jamanetworkopen.2019.18254.
IMPORTANCE: Insomnia disorder is prevalent and associated with health risks in older adults; however, efficacy and safety issues with existing treatments create significant unmet needs in this patient population. OBJECTIVE: To compare treatment with the orexin receptor antagonist lemborexant with placebo and zolpidem tartrate extended release in participants with insomnia disorder. DESIGN, SETTING, AND PARTICIPANTS: The Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1) clinical trial was a global randomized double-blind parallel-group placebo-controlled active-comparator phase 3 study conducted at 67 sites in North America and Europe from May 31, 2016, to January 30, 2018. Data analyses were conducted from January 31, 2018, to September 10, 2018. Participants were 55 years and older with insomnia disorder characterized by reported sleep maintenance difficulties and confirmed by sleep history, sleep diary, and polysomnography. Participants could have also had sleep onset difficulties. INTERVENTIONS: Participants received placebo, zolpidem tartrate extended release (6.25 mg), or lemborexant (5 mg or 10 mg) for 1 month at bedtime. MAIN OUTCOMES AND MEASURES: Paired polysomnograms were collected at baseline, the first 2 nights, and the last 2 nights of treatment. The primary end point was the change from baseline in latency to persistent sleep for lemborexant therapy vs placebo. Key secondary end points were changes from baseline in sleep efficiency and wake-after-sleep onset compared with placebo, and wake-after-sleep onset in the second half of the night compared with zolpidem therapy. RESULTS: Among 1006 participants randomized (placebo, n = 208; zolpidem, n = 263; lemborexant 5 mg, n = 266; and lemborexant 10 mg, n = 269), 869 (86.4%) were women and the median age was 63 years (range, 55-88 years). Both doses of lemborexant therapy demonstrated statistically significant greater changes from baseline on objective sleep onset as assessed by latency to persistent sleep (log transformed) that was measured using polysomnography at the end of 1 month of treatment (nights 29 and 30) compared with placebo (primary end point for least squares geometric means treatment ratio vs placebo: for lemborexant 5 mg, 0.77; 95% CI, 0.67-0.89; P < .001; for lemborexant 10 mg, 0.72; 95% CI, 0.63-0.83; P < .001). For nights 29 and 30, as measured using polysomnography, the mean change from baseline in sleep efficiency (LSM treatment difference vs placebo for lemborexant 5 mg, 7.1%; 95% CI, 5.6%-8.5%; P < .001 and for lemborexant 10 mg, 8.0%; 95% CI, 6.6%-9.5%; P < .001) and wake-after-sleep onset (least squares mean treatment ratio vs placebo for lemborexant 5 mg, -24.0 min; 95% CI, -30.0 to -18.0 min; P < .001 and for lemborexant 10 mg, -25.4 min; 95% CI, -31.4 to -19.3 min; P < .001) were significantly greater for both doses of lemborexant therapy compared with placebo. Also, for nights 29 and 30, wake-after-sleep onset in the second half of the night (least squares mean treatment difference vs zolpidem for lemborexant 5 mg, -6.7 min; 95% CI, -11.2 to -2.2 min; P = .004 and for lemborexant 10 mg, -8.0 min; 95% CI, -12.5 to -3.5 min; P < .001) was significantly greater for both doses of lemborexant therapy compared with zolpidem therapy measured using polysomnography. Six participants (4 in the zolpidem group and 2 in the lemborexant 5 mg group) reported serious adverse events; none were treatment-related. Other adverse events were mostly mild or moderate in severity. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, lemborexant therapy significantly improved both sleep onset and sleep maintenance, including in the second half of the night, compared with both placebo and zolpidem measured objectively using polysomnography. Lemborexant therapy was well tolerated. TRIAL REGISTRATIONS: ClinicalTrials.gov identifier: NCT02783729; EudraCT identifier: 2015-001463-39.
133Insomnia in Elderly Patients: Recommendations for Pharmacological Management.PubMed
Vivien C Abad, Christian Guilleminault
Drugs Aging. 2018 Sep;35(9):791-817. doi: 10.1007/s40266-018-0569-8.
Chronic insomnia affects 57% of the elderly in the United States, with impairment of quality of life, function, and health. Chronic insomnia burdens society with billions of dollars in direct and indirect costs of care. The main modalities in the treatment of insomnia in the elderly are psychological/behavioral therapies, pharmacological treatment, or a combination of both. Various specialty societies view psychological/behavioral therapies as the initial treatment intervention. Pharmacotherapy plays an adjunctive role when insomnia symptoms persist or when patients are unable to pursue cognitive behavioral therapies. Current drugs for insomnia fall into different classes: orexin agonists, histamine receptor antagonists, non-benzodiazepine gamma aminobutyric acid receptor agonists, and benzodiazepines. This review focuses on Food and Drug Administration (FDA)-approved drugs for insomnia, including suvorexant, low-dose doxepin, Z-drugs (eszopiclone, zolpidem, zaleplon), benzodiazepines (triazolam, temazepam), and ramelteon. We review the indications, dosing, efficacy, benefits, and harms of these drugs in the elderly, and discuss data on drugs that are commonly used off-label to treat insomnia, and those that are in clinical development. The choice of a hypnotic agent in the elderly is symptom-based. Ramelteon or short-acting Z-drugs can treat sleep-onset insomnia. Suvorexant or low-dose doxepin can improve sleep maintenance. Eszopiclone or zolpidem extended release can be utilized for both sleep onset and sleep maintenance. Low-dose zolpidem sublingual tablets or zaleplon can alleviate middle-of-the-night awakenings. Benzodiazepines should not be used routinely. Trazodone, a commonly used off-label drug for insomnia, improves sleep quality and sleep continuity but carries significant risks. Tiagabine, sometimes used off-label for insomnia, is not effective and should not be utilized. Non-FDA-approved hypnotic agents that are commonly used include melatonin, diphenhydramine, tryptophan, and valerian, despite limited data on benefits and harms. Melatonin slightly improves sleep onset and sleep duration, but product quality and efficacy may vary. Tryptophan decreases sleep onset in adults, but data in the elderly are not available. Valerian is relatively safe but has equivocal benefits on sleep quality. Phase II studies of dual orexin receptor antagonists (almorexant, lemborexant, and filorexant) have shown some improvement in sleep maintenance and sleep continuity. Piromelatine may improve sleep maintenance. Histamine receptor inverse agonists (APD-125, eplivanserin, and LY2624803) improve slow-wave sleep but, for various reasons, the drug companies withdrew their products.
134Melatonin use during pregnancy and lactation: A scoping review of human studies.PubMed
Tya Vine, Gregory M Brown, Benicio N Frey
Braz J Psychiatry. 2022 May-Jun;44(3):342-348. doi: 10.1590/1516-4446-2021-2156.
OBJECTIVE: The prevalence of sleep disorders during the perinatal period is high and large health administrative database surveys have shown that the use of exogenous melatonin in pregnant populations is quite common, about 4%. Much of the concern about using melatonin during pregnancy and breastfeeding stems from animal research. Thus, the objective of this article is to provide a critical review of human studies related to exogenous melatonin use during pregnancy and breastfeeding. METHODS: The electronic databases Ovid, MEDLINE, Embase, and the Cochrane Library were searched using terms and keywords related to melatonin, pregnancy, and breastfeeding. RESULTS: Fifteen studies were included in this review. Eight focused on melatonin use during pregnancy and seven focused on melatonin use during breastfeeding. There was a variety of study designs, including case reports, cohort studies, and clinical trials. There is a lack of randomized, controlled trials examining the efficacy and safety of melatonin as a treatment for sleep disorders during pregnancy or breastfeeding and, notably, insomnia was not the primary outcome measure in any of the studies included in this review. Clinical trials that used exogenous melatonin during pregnancy and breastfeeding for other clinical conditions have not suggested major safety concerns or adverse events. CONCLUSION: Contrary to what animal studies have suggested, evidence from clinical studies to date suggests that melatonin use during pregnancy and breastfeeding is probably safe in humans. This review further emphasizes the need for clinical studies on sleep disorders, including exogenous melatonin, during pregnancy and lactation.
135Efficacy of Digital Cognitive Behavioral Therapy for the Treatment of Insomnia Symptoms Among Pregnant Women: A Randomized Clinical Trial.PubMed
Jennifer N Felder, Elissa S Epel, John Neuhaus, et al.
JAMA Psychiatry. 2020 May 1;77(5):484-492. doi: 10.1001/jamapsychiatry.2019.4491.
IMPORTANCE: Despite the prevalence and adverse consequences of prenatal insomnia, a paucity of research is available regarding interventions to improve insomnia symptoms during pregnancy. OBJECTIVE: To test the efficacy of digital cognitive behavioral therapy for insomnia (CBT-I) compared with standard treatment among pregnant women with insomnia symptoms. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial enrolled pregnant women from November 23, 2016, to May 22, 2018. Of the 2258 women assessed for eligibility using an online self-report questionnaire, 208 were randomized to receive digital CBT-I (n = 105) or standard treatment (n = 103) for insomnia. Participants were pregnant up to 28 weeks' gestation, and they either had elevated insomnia symptom severity or met the criteria for insomnia caseness as determined by self-report questionnaires. Participants completed outcome measures at 10 weeks (postintervention) and 18 weeks (follow-up) after randomization. All study visits were completed remotely, and the intervention was delivered digitally. Data were analyzed between December 12, 2018, and July 2, 2019. INTERVENTIONS: Digital CBT-I consisted of 6 weekly sessions of approximately 20 minutes each. Standard treatment reflected standard care. Women receiving standard treatment had no limits placed on the receipt of nonstudy treatments, including medication and psychotherapy. MAIN OUTCOMES AND MEASURES: All outcomes were assessed remotely using self-report questionnaires administered via online survey. The primary outcome was the change in insomnia symptom severity (measured by the Insomnia Severity Index) from baseline to postintervention. Secondary outcomes were sleep efficiency and nightly sleep duration (defined by sleep diary), global sleep quality (measured by the Pittsburgh Sleep Quality Index), depressive symptom severity (measured by the Edinburgh Postnatal Depression Scale), and anxiety symptom severity (measured by the Generalized Anxiety Disorder Scale-7). For each outcome, we also examined the change from baseline to follow-up. RESULTS: The 208 participants had a mean (SD) age of 33.6 (3.7) years and a mean (SD) gestational age of 17.6 (6.3) weeks at baseline. Most of the participants were white (138 [66.3%]), married or cohabiting (196 [94.2%]), had a college degree (180 [86.5%]), and earned $100 000 or more per year (141 [67.8%]). Women randomized to receive digital CBT-I experienced statistically significantly greater improvements in insomnia symptom severity from baseline to postintervention compared with women randomized to receive standard treatment (time-by-group interaction, difference = -0.36; 95% CI, -0.48 to -0.23; χ2 = 29.8; P < .001; d = -1.03). Improvements from baseline to postintervention for all secondary outcomes, with the exception of sleep duration, were statistically significant. A similar pattern of results was evident for the change from baseline to follow-up. CONCLUSIONS AND RELEVANCE: In this trial, digital CBT was an effective, scalable, safe, and acceptable intervention for improving insomnia symptoms during pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02805998.
136Perinatal DepressionPubMed
Karen Carlson, Saba Mughal, Yusra Azhar, et al.
Perinatal depression is a mood disorder that affects individuals during pregnancy or within 1 year after childbirth. According to the (), postpartum depression is now included in the term perinatal depression. A major depressive episode that begins during pregnancy or within 4 weeks after delivery is classified as peripartum depression. This term encompasses both prenatal and postpartum depression. The does not recognize postpartum depression as a separate entity. Instead, postpartum depression is included within the broader diagnosis of perinatal depression. Depression symptoms, including persistent sadness, lack of interest, low self-esteem, sleep disturbances, loss of appetite, anxiety, irritability with a hostile attitude towards infants, self-blame, and feelings of humiliation characterize perinatal depression. People with perinatal depression may also experience changes in sleeping and eating patterns, difficulty bonding with their baby, and feelings of hopelessness or worthlessness. In contrast, postpartum blues, also known as maternity blues or baby blues, includes mild, transient depressive symptoms and dysphoria during the first days to weeks after delivery. Symptoms of postpartum blues are similar to perinatal depression, including tearfulness, crying spells, sorrow, mood swings, irritability, insomnia, anxiety, poor appetite, fatigue, and inability to think clearly. However, unlike postpartum blues, which typically resolves within a few weeks, does not cause significant functional impairment, and is not considered to be a mental disorder, perinatal depression is more severe. It can last for months if untreated, resulting in significant mental health dysfunction. Recognizing and addressing perinatal depression is crucial for the health and well-being of the patient and their baby. If left untreated, perinatal depression can interfere with the ability to care for the child. It may contribute to long-term developmental issues in the child (eg, emotional and behavioral problems). Perinatal depression can also strain family relationships and increase the risk of suicide. Screening for perinatal depression should be a routine part of prenatal and postpartum care, utilizing tools such as the Edinburgh Postnatal Depression Scale (EPDS) to identify those at risk. Treatment typically involves a combination of psychotherapy, support groups, and medication, including antidepressants, which can safely be used during pregnancy and lactation. Up to 50% of perinatal depression cases remain undiagnosed due to patient reluctance to disclose symptoms, partly because of the stigma around perinatal depression, which includes fears of abandonment and lack of support upon disclosure. Raising awareness about perinatal depression, reducing stigma, and ensuring access to mental health resources are essential steps in supporting pregnant people and new parents to promote healthy family dynamics.
137Treatment of insomnia - effect of trazodone and hypnotics on sleep.PubMed
Adam Wichniak, Aleksandra Ewa Wierzbicka, Marek Jarema
Psychiatr Pol. 2021 Aug 31;55(4):743-755. doi: 10.12740/PP/125650.
Sedative antidepressants are commonly used drugs in the treatment of insomnia. However, some recommendations claim that only hypnotics have been proven effective in the treatment of sleep initiation and maintenance disorders. The aim of this article is to compare the effect of hypnotics and trazodone on sleep, and to analyse the evidence for the use of trazodone in the treatment of insomnia. Three studies investigated the effects of trazodone on sleep in primary insomnia, 5 studies on insomnia in the course of affective disorders and 6 studies on insomnia in other indications (PTSD, Alzheimer's disease, alcohol and opiate dependence, somatoform disorder, and insomnia during pregnancy). In the treatment of insomnia, trazodone is less effective than hypnotics in the treatment of sleep onset insomnia (i.e., disorders of falling asleep). For this indication it needs to be administered earlier than hypnotics, at least 1 hour before bedtime. It is, however, very effective in the treatment of sleep-maintenance insomnia, especially in patients with comorbid mental disorders or patients treated with activating antidepressants. Hypnotics and trazodone have the opposite effect on deep sleep. Trazodone increases the duration of deep sleep, which is associated with better sleep quality as assessed by patients. In contrast, hypnotics decrease slow-wave activityin sleep EEG, which is the biomarker of deep sleep. The main mechanism through which trazodone promotes sleep is its antagonistic effect on 5-HT2 serotonin receptors, while hypnotics are agonists of gamma-aminobutyric acid GABAA receptors, and other sedative antidepressants block H1 histamine receptors. This is associated with a low risk of weight gain, which is rare with trazodone treatment.
138Patient Self-Guided Interventions to Reduce Sedative Use and Improve Sleep: The YAWNS NB Randomized Clinical Trial.PubMed
David M Gardner, Justin P Turner, Sandra Magalhaes, et al.
JAMA Psychiatry. 2024 Dec 1;81(12):1187-1197. doi: 10.1001/jamapsychiatry.2024.2731.
IMPORTANCE: Direct-to-patient interventions enabling transitions from long-term benzodiazepine receptor agonist (BZRA) use to cognitive behavioral therapy for insomnia (CBTI) by older adults has the potential to reduce BZRA use and related harms while improving sleep outcomes without requiring prearranged clinician involvement. OBJECTIVE: To compare 2 direct-to-patient behavior change interventions with treatment as usual (TAU) on BZRA use, sleep, and other health outcomes, and uptake of CBTI techniques. DESIGN, SETTING, AND PARTICIPANTS: The Your Answers When Needing Sleep in New Brunswick (YAWNS NB) study was a 3-arm, pragmatic, open-label, minimum-contact, randomized clinical trial. The study began November 2020 and ended June 2022. Participants were randomly allocated to 1 of 3 groups, including 2 different mailed behavior change interventions or no intervention (TAU). Participants were from communities across the province of New Brunswick, Canada, and included adults 65 years and older living independently with long-term use of BZRAs and current or past insomnia. INTERVENTIONS: The Sleepwell package (YAWNS-1) consisted of a cover letter and 2 booklets ("How to Stop Sleeping Pills" and "How to Get Your Sleep Back"). The other package (YAWNS-2) included updated versions of the 2 booklets ("You May Be at Risk" and "How to Get a Good Night's Sleep Without Medication") used in the Eliminating Medications Through Patient Ownership of End Results (EMPOWER) study. MAIN OUTCOMES AND MEASURES: BZRA use at 6 months was the primary measure. Secondary measures included CBTI use, sleep, insomnia, daytime sleepiness, safety, anxiety, frailty, and quality of life. RESULTS: A total of 1295 individuals expressed interest in the study, and 565 (43.6%) completed a baseline assessment. Participants had a mean (SD) age of 72.1 (5.7) years, a mean (SD) BZRA use duration of 11.4 (9.1) years, and 362 (64.1%) were female. Discontinuations and dose reductions of 25% or greater were highest with YAWNS-1 (50 of 191 [26.2%]; 39 of 191 [20.4%]; total, 46.6%) compared with YAWNS-2 (38 of 187 [20.3%]; 27 of 187 [14.4%]; total, 34.8%, P = .02) and TAU (14 of 187 [7.5%]; 24 of 187 [12.8%]; total, 20.3%, P < .001). YAWNS-1 also demonstrated better uptake of CBTI techniques and sleep outcomes compared with YAWNS-2 (new CBTI techniques: 3.1 vs 2.4; P =.03; sleep efficiency change: 4.1% vs -1.7%; P =.001) and reduced insomnia severity and daytime sleepiness compared with TAU (insomnia severity index change: -2.0 vs 0.3; P <.001; Epworth Sleepiness Scale change: -0.8 vs 0.3; P =.001). CONCLUSIONS AND RELEVANCE: Results of the YAWNS NB randomized clinical trial show that, as a simple, scalable, direct-to-patient intervention, YAWNS-1 substantially reduced BZRA use and improved sleep outcomes. It could be implemented to transform insomnia care for older adults at the population level. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04406103.
139Chronic insomnia.PubMed
Charles M Morin, Ruth Benca
Lancet. 2012 Mar 24;379(9821):1129-41. doi: 10.1016/S0140-6736(11)60750-2. Epub 2012 Jan 20.
Insomnia is a prevalent complaint in clinical practice that can present independently or comorbidly with another medical or psychiatric disorder. In either case, it might need treatment of its own. Of the different therapeutic options available, benzodiazepine-receptor agonists (BzRAs) and cognitive-behavioural therapy (CBT) are supported by the best empirical evidence. BzRAs are readily available and effective in the short-term management of insomnia, but evidence of long-term efficacy is scarce and most hypnotic drugs are associated with potential adverse effects. CBT is an effective alternative for chronic insomnia. Although more time consuming than drug management, CBT produces sleep improvements that are sustained over time, and this therapy is accepted by patients. Although CBT is not readily available in most clinical settings, access and delivery can be made easier through use of innovative methods such as telephone consultations, group therapy, and self-help approaches. Combined CBT and drug treatment can optimise outcomes, although evidence to guide clinical practice on the best way to integrate these approaches is scarce.
140Sequential combinations of drug and cognitive behavioral therapy for chronic insomnia: an exploratory study.PubMed
Annie Vallières, Charles M Morin, Bernard Guay
Behav Res Ther. 2005 Dec;43(12):1611-30. doi: 10.1016/j.brat.2004.11.011.
This study explores the efficacy of sequential treatments involving medication and cognitive behavioral treatment (CBT) for primary insomnia. Seventeen participants took part in a multiple baseline design and were assigned to: (a) medication for 5 weeks, followed by combined medication plus CBT for 5 weeks; (b) combined treatment for 5 weeks, followed by CBT alone; or (c) CBT alone. Each treatment sequence produced significant sleep improvements, but at different points in time. For the first sequence, most of the sleep improvement was obtained after the introduction of CBT, while for the other sequence and CBT alone, improvement appeared during the first weeks. These results suggest that sleep improvement seems affected by the way treatments are combined. Also, a sequence beginning with a combined treatment followed by CBT alone seems to produce the best outcome. Additional research should be conducted with larger samples to determine the most effective sequence.
141Sequential treatment for chronic insomnia: a pilot study.PubMed
Annie Vallières, Charles M Morin, Bernard Guay, et al.
Behav Sleep Med. 2004;2(2):94-112. doi: 10.1207/s15402010bsm0202_2.
This article explores the efficacy of sequential treatment involving medication and cognitive behavioral treatment (CBT) for insomnia. In a multiple baseline across-subjects design, 6 participants with primary chronic insomnia received 1 of the following treatment sequences: (a) concurrent combination of medication and CBT for the 10-week treatment duration (Combined); (b) medication for the first 5 weeks, with introduction of CBT at week 4 and medication withdrawal after the 5th week resulting in treatment overlap during weeks 4 and 5 (Overlapping: Medication --> Combined --> CBT); and (c) medication alone for the first 5 weeks followed by CBT alone for an additional 5 weeks (Medication --> CBT). Each sequence led to significant sleep improvements, but these improvements occurred at different times during the intervention. Participants in the Combined and in the Overlapping sequences improved their sleep during the 1st phase of treatment, whereas those in the Medication --> CBT sequence improved mostly during the 2nd phase of treatment. These preliminary results suggest that a sequential treatment is effective for chronic insomnia. In addition, the results suggest that sleep improvements are more likely to emerge when CBT is introduced, with an Overlapping sequence showing a slight advantage over the other sequences. Additional clinical trials should be conducted with larger samples to replicate these preliminary findings.
142Moderators of Cognitive Behavioral Treatment for Insomnia on Depression and Anxiety Outcomes.PubMed
Riya Mirchandaney, Raul Barete, Lauren D Asarnow
Curr Psychiatry Rep. 2022 Feb;24(2):121-128. doi: 10.1007/s11920-022-01326-3. Epub 2022 Jan 21.
PURPOSE OF REVIEW: With a focus on reviewing adequately powered randomized controlled trials, we present recent research on the potential of cognitive behavioral therapy for insomnia (CBT-I) to improve depression and anxiety outcomes among patients with insomnia and one of the following comorbid psychiatric disorders: major depressive disorder (MDD), generalized anxiety disorder (GAD), or posttraumatic stress disorder (PTSD). We also examine potential moderators of CBT-I on depression and anxiety outcomes in this population. RECENT FINDINGS: Despite high comorbidity rates, current behavioral and pharmacological treatments for MDD, GAD, and PTSD do not substantially target or improve insomnia symptoms; residual insomnia is exceedingly common even among patients who experience remission. Insomnia plays a critical role in the onset and maintenance of depression and anxiety, and treating insomnia with CBT-I may improve global outcomes for patients with MDD, GAD, and PTSD. CBT-I is superior to traditional depression/anxiety treatment in improving insomnia symptoms among patients with comorbid psychiatric disorders. Results are mixed on whether CBT-I (either alone or augmented with depression/anxiety treatment) is effective in improving overall MDD, GAD, and PTSD outcomes. Evening circadian preference and depression/anxiety symptom severity may moderate the effect of CBT-I on depression and anxiety outcomes.
143Pharmacological Management of Insomnia.PubMed
Sarika Madari, Raphael Golebiowski, Meghna P Mansukhani, et al.
Neurotherapeutics. 2021 Jan;18(1):44-52. doi: 10.1007/s13311-021-01010-z. Epub 2021 Feb 1.
Insomnia is a highly prevalent condition associated with significant morbidity, reduction in quality of life, and increase in healthcare costs, and is a risk factor for multiple physical and mental disorders. The primary treatment modality is cognitive behavioral therapy for insomnia (CBT-I) but this is associated with difficulties with access and higher cost as well as poor response in some patients. Therefore, pharmacotherapy for insomnia is common and hypnotic agents are among the most frequently prescribed medications in the United States. Older medications for insomnia are limited by their side effect burden and narrow therapeutic window. Newer hypnotics, on the other hand, have been shown to have a better safety profile and longer term efficacy. While some studies have shown that long-term hypnotic use is associated with adverse outcomes, the current evidence is equivocal. The decision to treat chronic insomnia disorder with long-term hypnotics should be individualized and balance the potential risks of continuing hypnotic medication use with the risks of untreated persistent insomnia and associated functional limitations. This clinical review discusses the currently available medication options to treat insomnia, their mechanisms of action, dosing, and side effect profiles. This review also provides guidance on long-term management of hypnotics and the use of these medications in the elderly, those with medical comorbidities, and other special populations.
144Management of insomnia.PubMed
C K Kirkwood
J Am Pharm Assoc (Wash). 1999 Sep-Oct;39(5):688-96; quiz 713-4. doi: 10.1016/s1086-5802(15)30354-5.
OBJECTIVE: To review current issues in the pharmacologic and nonpharmacologic management of insomnia. DATA SOURCES: Controlled trials and case studies identified via MEDLINE for 1990 through April 1999 under the search terms insomnia, hypnotics, flurazepam, quazepam, estazolam, temazepam, triazolam, zolpidem, zaleplon, L-846, CL-284,846, melatonin, and valerian. DATA SYNTHESIS: Insomnia is a common, undertreated disorder. Nonpharmacologic management strategies (e.g., stimulus control, relaxation therapy, sleep hygiene) are therapeutic options that, compared with medication use, provide more sustained effects. The benzodiazepines and zolpidem are the most commonly prescribed hypnotic agents, but their use is associated with tolerance and central nervous system adverse effects. A new nonbenzodiazepine hypnotic agent, zaleplon, was very recently approved in the United States. Because of its short half-life, zaleplon will be useful in patients experiencing difficulty in falling asleep and in those who wake up at night and have trouble falling back to sleep. Antidepressants, antihistamines, and alternative medications are other treatment options. To avoid complications of therapy, hypnotic agents should be used at their lowest possible doses and for limited treatment durations. CONCLUSION: Pharmacotherapy is currently the most common treatment modality for insomnia, but long-term use of hypnotic agents can become complicated by drug tolerance, dependence, or rebound insomnia. Nonpharmacologic options--including combinations of behavioral interventions, sleep-restriction therapy, and patient education--provide longer-lasting benefits.
145Opioid and benzodiazepine tolerance and dependence: application of theory to critical care practice.PubMed
K Puntillo, V Casella, M Reid
Heart Lung. 1997 Jul-Aug;26(4):317-24. doi: 10.1016/s0147-9563(97)90089-3.
Critical care clinicians frequently manage patient pain and agitation and promote ventilator stability through use of opioids and benzodiazepines. Often, doses of these drugs must be increased considerably over time as they lose their effectiveness-an indication of drug tolerance. Furthermore, patients can experience negative physiologic responses to withdrawal of these drugs-an indication of drug dependence. Withdrawal symptoms due to abrupt discontinuation of drug therapy can be profound and dangerous. It is important that clinicians understand the mechanisms of drug therapies and their potential negative sequelae. The purpose of this article is to present physiologic theories of opioid and benzodiazepine actions, as well as drug tolerance and dependence, as a basis of knowledge for clinical practice. A clinical scenario of an intensive care unit patient is presented, and a care plan is offered, to provide guidance to practitioners who care for patients experiencing the consequences of long-term opioid and benzodiazepine use.
146Sedative-hypnotics: pharmacology and use.PubMed
N S Miller, M S Gold
J Fam Pract. 1989 Dec;29(6):665-70.
The quest for an ideal sedative-hypnotic drug has been fraught with failure. The goals of the perfect sedative-hypnotic drug are to: (1) produce a transient reduction in the level of consciousness for the purpose of sedation, calmness, and tranquility without lingering aftereffects; (2) produce sleep without the potential to arrest respirations and without aftereffects on sensorium and mood; and (3) produce no abuse, addiction, tolerance, or dependence. Nonetheless, clinical conditions have required the use of sedative-hypnotic drugs in spite of the inherent difficulties with them. The history of sedative-hypnotic drugs is replete with attempts to produce a safe and effective drug. The introduction of one sedative-hypnotic drug for another has been heralded by unguarded optimism and misguided claims. History has repeated itself with each new drug. Toxicities, abuse, addiction, and development of tolerance and dependence have remained in force for each drug that has appeared on the market. Only minor variations on a theme have differentiated one drug from another as the essential features have remained in force.
147Tolerance and withdrawal issues with sedation.PubMed
Antonia Zapantis, Simon Leung
Crit Care Nurs Clin North Am. 2005 Sep;17(3):211-23. doi: 10.1016/j.ccell.2005.04.011.
The stay in an ICU is a complex mixture of providing optimal care while keeping the patient safe. Means of reducing the anxiety associated with the ICU stay include frequent reorientation and maintenance of patient comfort with sedation supplemented by analgesia as needed. The most common agents used to provide sedation include benzodiazepines, propofol, and the newer dexmedetomidine. Others include barbiturate agents, neuroleptics, clonidine, etomidate, ketamine, and supplemental opioid analgesics for pain control. A common complication of sedation is tolerance, which can lead to withdrawal if the sedation is discontinued hastily. This article evaluates the occurrence of tolerance and withdrawal in the most commonly used sedatives in critically ill patients.
148Efficacy and safety of Z-substances in the management of insomnia in older adults: a systematic review for the development of recommendations to reduce potentially inappropriate prescribing.PubMed
Vincenz Scharner, Lukas Hasieber, Andreas Sönnichsen, et al.
BMC Geriatr. 2022 Feb 1;22(1):87. doi: 10.1186/s12877-022-02757-6.
BACKGROUND: Z-drugs are usually prescribed as first line pharmacological therapy for insomnia. However, the benefits and risks of Z-drugs may differ for older adults. This systematic review investigated the available evidence on the efficacy and safety of Z-drugs in the management of insomnia in older adults. METHODS: The Cochrane database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed/MEDLINE and EMBASE were searched for systematic reviews, meta-analyses, controlled interventional and observational studies using a pre-formulated search term. The target population was older adults (≥65 years old) with insomnia. Studies were included if they reported efficacy and/or safety outcomes of the use of Z-drugs for the management of insomnia compared to placebo, usual or no treatment, or other pharmacological agents. RESULTS: Eighteen studies were included (8 interventional and 10 observational studies). In short-term interventional studies, Z-drugs were similarly or better efficacious in improving both sleep and daytime parameters than placebo or other pharmacological treatments, while showing good results on measures of safety. However, in longer-term observational studies, Z-drugs significantly increased the risk for falls and fractures in comparison to no treatment or melatonin agonists. CONCLUSIONS: Analyzing the evidence from short-term interventional studies, Z-drugs appear effective and safe for treatment of insomnia in older adults, but they may have unfavorable side effects when used for longer periods of time. We, therefore, recommend discontinuing Z-drugs, principally because of the high risk for falls and fractures. Nonetheless, quality and quantity of evidence are low. Due to the scarcity of data, especially concerning drug dependence after longer periods of treatment and due to the significantly increased risk for falls and fractures, further studies are needed to evaluate the benefit-risk profile of Z-drugs use in older patients, particularly for long-term use.
149Sleep in Normal Aging.PubMed
Junxin Li, Michael V Vitiello, Nalaka S Gooneratne
Sleep Med Clin. 2018 Mar;13(1):1-11. doi: 10.1016/j.jsmc.2017.09.001. Epub 2017 Nov 21.
Sleep patterns change with aging, independent of other factors, and include advanced sleep timing, shortened nocturnal sleep duration, increased frequency of daytime naps, increased number of nocturnal awakenings and time spent awake during the night, and decreased slow wave sleep. Most of these changes seem to occur between young and middle adulthood; sleep parameters remain largely unchanged among healthy older adults. The circadian system and sleep homeostatic mechanisms become less robust with normal aging. The amount and pattern of sleep-related hormone secretion change as well. The causes of sleep disturbances in older adults are multifactorial.
150Sleep in the Elderly.PubMed
Prathusha Tatineny, Fariha Shafi, Ashraf Gohar, et al.
Mo Med. 2020 Sep-Oct;117(5):490-495.
Aging is associated with several changes in sleep patterns. Older adults have increased prevalence of primary sleep disorders including insomnia, sleep disordered breathing, restless legs syndrome, REM sleep behavior disorder, and circadian rhythm disturbances. These can be further compromised by sleep disturbances secondary to medical or psychiatric disorders, and medication side effects. This review discusses age-related changes in sleep architecture, etiology, clinical presentation, and treatment options of various sleep disorders in the elderly.
151Sleep in Normal Aging.PubMed
Junxin Li, Michael V Vitiello, Nalaka S Gooneratne
Sleep Med Clin. 2022 Jun;17(2):161-171. doi: 10.1016/j.jsmc.2022.02.007.
Sleep is a key determinant of healthy and cognitive aging. Sleep patterns change with aging, independent of other factors, and include advanced sleep timing, shortened nocturnal sleep duration, increased frequency of daytime naps, increased number of nocturnal awakenings and time spent awake during the night, and decreased slow-wave sleep. The sleep-related hormone secretion changes with aging. Most changes seem to occur between young and middle adulthood; sleep parameters remain largely unchanged among healthy older adults. The circadian system and sleep homeostatic mechanisms become less robust with normal aging. The causes of sleep disturbances in older adults are multifactorial.
152Aging-related sleep changes.PubMed
Joseph Roland D Espiritu
Clin Geriatr Med. 2008 Feb;24(1):1-14, v. doi: 10.1016/j.cger.2007.08.007.
Normal aging is accompanied by changes in the sleep quality, quantity, and architecture. Specifically, there appears to be a measurable decrease in the ability of the healthy elderly to initiate and maintain sleep, accompanied by a decrease in the proportion of the deeper, more restorative slow-wave sleep and rapid eye movement sleep. There is epidemiologic evidence that this impaired ability to initiate, maintain, and ultimately achieve good quality, optimal sleep may be a marker of increased mortality and neurocognitive dysfunction. Possible mechanisms related to these age-related changes in sleep include age-related changes in circadian modulation, homeostatic factors, cardiopulmonary function, and endocrine function. This article describes the normal changes in sleep physiology in the elderly.
153Sleep Architecture, Obstructive Sleep Apnea, and Cognitive Function in Adults.PubMed
Matthew P Pase, Stephanie Harrison, Jeffrey R Misialek, et al.
JAMA Netw Open. 2023 Jul 3;6(7):e2325152. doi: 10.1001/jamanetworkopen.2023.25152.
IMPORTANCE: Good sleep is essential for health, yet associations between sleep and dementia risk remain incompletely understood. The Sleep and Dementia Consortium was established to study associations between polysomnography (PSG)-derived sleep and the risk of dementia and related cognitive and brain magnetic resonance imaging endophenotypes. OBJECTIVE: To investigate association of sleep architecture and obstructive sleep apnea (OSA) with cognitive function in the Sleep and Dementia Consortium. DESIGN, SETTING, AND PARTICIPANTS: The Sleep and Dementia Consortium curated data from 5 population-based cohorts across the US with methodologically consistent, overnight, home-based type II PSG and neuropsychological assessments over 5 years of follow-up: the Atherosclerosis Risk in Communities study, Cardiovascular Health Study, Framingham Heart Study (FHS), Osteoporotic Fractures in Men Study, and Study of Osteoporotic Fractures. Sleep metrics were harmonized centrally and then distributed to participating cohorts for cohort-specific analysis using linear regression; study-level estimates were pooled in random effects meta-analyses. Results were adjusted for demographic variables, the time between PSG and neuropsychological assessment (0-5 years), body mass index, antidepressant use, and sedative use. There were 5946 participants included in the pooled analyses without stroke or dementia. Data were analyzed from March 2020 to June 2023. EXPOSURES: Measures of sleep architecture and OSA derived from in-home PSG. MAIN OUTCOMES AND MEASURES: The main outcomes were global cognitive composite z scores derived from principal component analysis, with cognitive domains investigated as secondary outcomes. Higher scores indicated better performance. RESULTS: Across cohorts, 5946 adults (1875 females [31.5%]; mean age range, 58-89 years) were included. The median (IQR) wake after sleep onset time ranged from 44 (27-73) to 101 (66-147) minutes, and the prevalence of moderate to severe OSA ranged from 16.9% to 28.9%. Across cohorts, higher sleep maintenance efficiency (pooled β per 1% increase, 0.08; 95% CI, 0.03 to 0.14; P < .01) and lower wake after sleep onset (pooled β per 1-min increase, -0.07; 95% CI, -0.13 to -0.01 per 1-min increase; P = .02) were associated with better global cognition. Mild to severe OSA (apnea-hypopnea index [AHI] ≥5) was associated with poorer global cognition (pooled β, -0.06; 95% CI, -0.11 to -0.01; P = .01) vs AHI less than 5; comparable results were found for moderate to severe OSA (pooled β, -0.06; 95% CI, -0.11 to -0.01; P = .02) vs AHI less than 5. Differences in sleep stages were not associated with cognition. CONCLUSIONS AND RELEVANCE: This study found that better sleep consolidation and the absence of OSA were associated with better global cognition over 5 years of follow-up. These findings suggest that the role of interventions to improve sleep for maintaining cognitive function requires investigation.
154[Treatment of insomnia in old age].PubMed
Kneginja Richter, Stefanie Kellner, Lence Miloseva, et al.
Z Gerontol Geriatr. 2020 Mar;53(2):105-111. doi: 10.1007/s00391-019-01684-3. Epub 2020 Jan 21.
Insomnia is one of the most frequent health disorders in old age. It causes suffering and numerous health problems. Therefore, treatment is often indicated. Behavioral therapy is the treatment of choice even in older individuals. In addition, light therapy also has an important role. Pharmacological treatment measures are less well studied, the benefits in long-term use are unclear and should only be applied in the short term to reduce suffering as well as being integrated into a comprehensive treatment concept.
155Prevention of Incident and Recurrent Major Depression in Older Adults With Insomnia: A Randomized Clinical Trial.PubMed
Michael R Irwin, Carmen Carrillo, Nina Sadeghi, et al.
JAMA Psychiatry. 2022 Jan 1;79(1):33-41. doi: 10.1001/jamapsychiatry.2021.3422.
IMPORTANCE: Older adults with insomnia have a high risk of incident and recurrent depression. Depression prevention is urgently needed, and such efforts have been neglected for older adults. OBJECTIVE: To examine whether treatment of insomnia disorder with cognitive behavioral therapy for insomnia (CBT-I) compared with an active comparator condition, sleep education therapy (SET), prevents major depressive disorder in older adults. DESIGN, SETTING, AND PARTICIPANTS: This assessor-blinded, parallel-group, single-site randomized clinical trial assessed a community-based sample of 431 people and enrolled 291 adults 60 years or older with insomnia disorder who had no major depression or major health events in past year. Study recruitment was performed from July 1, 2012, to April 30, 2015. The trial protocol was modified to extend follow-up from 24 to 36 months, with follow-up completion in July 2018. Data analysis was performed from March 1, 2019, to March 30, 2020. INTERVENTIONS: Participants were randomized to 2 months of CBT-I (n = 156) or SET (n = 135). MAIN OUTCOMES AND MEASURES: The primary outcome was time to incident major depressive disorder as diagnosed by interview and Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria. Secondary outcome was sustained remission of insomnia disorder before depression event or duration of follow-up. RESULTS: Among 291 randomized participants (mean [SD] age, 70.1 [6.7] years; 168 [57.7%] female; 7 [2.4%] Asian, 32 [11.0%] Black, 3 [1.0%] Pacific Islander, 241 [82.8%] White, 6 [2.1%] multiracial, and 2 [0.7%] unknown), 156 were randomized to CBT-I and 135 to SET. A total of 140 participants (89.7%) completed CBT-I and 130 (96.3%) participants completed SET (χ2 = 4.9, P = .03), with 114 (73.1%) completing 24 months of follow-up in the CBT-I group and 117 (86.7%) in the SET group (χ2 = 8.4, P = .004). After protocol modification, 92 (59.0%) of the CBT-I participants and 86 (63.7%) of the SET participants agreed to extended follow-up (χ2 = 0.7, P = .41), with 81 (51.9%) of the CBT-I participants and 77 (57.0%) of the SET group completing 36 months of follow-up (χ2 = 0.8; P = .39). Incident or recurrent major depression occurred in 19 participants (12.2%) in the CBT-I group and in 35 participants (25.9%) in the SET group, with an overall benefit (hazard ratio, 0.51; 95%, CI 0.29-0.88; P = .02) consistent across subgroups. Remission of insomnia disorder continuously sustained before depression event or during follow-up was more likely in CBT-I participants (41 [26.3%]) compared with the SET participants (26 [19.3%], P = .03). Those in the CBT-I group with sustained remission of insomnia disorder had an 82.6% decreased likelihood of depression (hazard ratio, 0.17; 95%, CI 0.04-0.73; P = .02) compared with those in the SET group without sustained remission of insomnia disorder. CONCLUSIONS AND RELEVANCE: The findings of this randomized clinical trial indicate that treatment of insomnia with CBT-I has an overall benefit in the prevention of incident and recurrent major depression in older adults with insomnia disorder. Community-level screening for insomnia concerns in older adults and wide delivery of CBT-I-based treatment for insomnia could substantially advance public health efforts to treat insomnia and prevent depression in this vulnerable older adult population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01641263.
156High dose melatonin increases sleep duration during nighttime and daytime sleep episodes in older adults.PubMed
Jeanne F Duffy, Wei Wang, Joseph M Ronda, et al.
J Pineal Res. 2022 Aug;73(1):e12801. doi: 10.1111/jpi.12801. Epub 2022 May 13.
Aging is associated with changes in sleep, and improving sleep may have important consequences for the health, cognition, and quality of life of older adults. Many prescription sleep aids increase the risk of nighttime falls, have adverse effects on next-day cognition, and are associated with increased mortality. Melatonin, a hormone secreted at night, increases sleep duration in young adults but only when administered during the day when endogenous levels are low. In a month-long cross-over study, we randomized 24 healthy older (age >55, mean 64.2 ± 6.3 years) participants to receive 2 weeks of placebo and 2 weeks of either a low (0.3 mg) or high (5.0 mg) dose of melatonin 30 min before lights out. Sleep was polysomnographically recorded and was scheduled during both the biological day and night using a forced desynchrony design. Although 0.3 mg melatonin had a trend towards increasing sleep efficiency (SE) overall, this was due to its effects on sleep during the biological day. In contrast, 5 mg melatonin significantly increased SE during both biological day and night, mainly by increasing the duration of Stage 2 non-rapid eye movement sleep and slightly shortening awakenings. Melatonin should be further explored as a sleep aid for older adults.
157Circadian Rhythm Sleep-Wake Disorders in Older Adults.PubMed
Jee Hyun Kim, Alexandria R Elkhadem, Jeanne F Duffy
Sleep Med Clin. 2022 Jun;17(2):241-252. doi: 10.1016/j.jsmc.2022.02.003.
The timing, duration, and consolidation of sleep result from the interaction of the circadian timing system with a sleep-wake homeostatic process. When aligned and functioning optimally, this allows for wakefulness throughout the day and a long consolidated sleep episode at night. Changes to either the sleep regulatory process or how they interact can result in an inability to fall asleep at the desired time, difficulty remaining asleep, waking too early, and/or difficulty remaining awake throughout the day. This mismatch between the desired timing of sleep and the ability to fall asleep and remain asleep is a hallmark of a class of sleep disorders called the circadian rhythm sleep-wake disorders. In this updated article, we discuss typical changes in the circadian regulation of sleep with aging; how age influences the prevalence, diagnosis, and treatment of circadian rhythm sleep disorders; and how neurologic diseases in older patient impact circadian rhythms and sleep.
158Circadian Rhythm Sleep-Wake Disorders.PubMed
Milena Pavlova
Continuum (Minneap Minn). 2017 Aug;23(4, Sleep Neurology):1051-1063. doi: 10.1212/CON.0000000000000499.
PURPOSE OF REVIEW: The endogenous circadian rhythms are one of the cardinal processes that control sleep. They are self-sustaining biological rhythms with a periodicity of approximately 24 hours that may be entrained by external zeitgebers (German for time givers), such as light, exercise, and meal times. This article discusses the physiology of the circadian rhythms, their relationship to neurologic disease, and the presentation and treatment of circadian rhythm sleep-wake disorders. RECENT FINDINGS: Classic examples of circadian rhythms include cortisol and melatonin secretion, body temperature, and urine volume. More recently, the impact of circadian rhythm on several neurologic disorders has been investigated, such as the timing of occurrence of epileptic seizures as well as neurobehavioral functioning in dementia. Further updates include a more in-depth understanding of the symptoms, consequences, and treatment of circadian sleep-wake disorders, which may occur because of extrinsic misalignment with clock time or because of intrinsic dysfunction of the brain. An example of extrinsic misalignment occurs with jet lag during transmeridian travel or with intrinsic circadian rhythm sleep-wake disorders such as advanced or delayed sleep-wake phase disorders. In advanced sleep-wake phase disorder, which is most common in elderly individuals, sleep onset and morning arousal are undesirably early, leading to impaired evening function with excessive sleepiness and sleep-maintenance insomnia with early morning awakening. By contrast, delayed sleep-wake phase disorder is characterized by an inability to initiate sleep before the early morning hours, with subsequent delayed rise time, leading to clinical symptoms of severe sleep-onset insomnia coupled with excessive daytime sleepiness in the morning hours, as patients are unable to "sleep in" to attain sufficient sleep quantity. Irregular sleep-wake rhythm disorder is misentrainment with patches of brief sleep and wakefulness spread throughout the day, leading to unstable sleep and waking behavioral patterns and an entirely idiosyncratic sleep-wake schedule. SUMMARY: Familiarity with these major circadian rhythm sleep-wake disorder phenotypes and their overlap with other neurologic disorders is essential for the neurologist so that clinicians may intervene and improve patient functioning and quality of life.
159Menopause and Sleep Disorders.PubMed
Vishal R Tandon, Sudhaa Sharma, Annil Mahajan, et al.
J Midlife Health. 2022 Jan-Mar;13(1):26-33. doi: 10.4103/jmh.jmh_18_22. Epub 2022 May 2.
Women are likely to suffer from sleep disorders more in comparison to men during menopause and with advancing age. The incidence of sleep disorders ranges from 16% to 47% at peri-menopause and 35%-60% at postmenopause. Insomnia with or without associated anxiety or low lying depression and Mood disorder is most common associated manifestations. Sleep disorders and insomnia largely remain a clinical diagnosis based on the subjective complaints of patients. Benzodiazepines remain the mainstay of the treatment in majority of the sleep disorders including chronic or acute insomnia. Treatment of associated anxiety, depression, or psychosis is most important. Tricyclic antidepressant, Selective Serotonin Reuptake Inhibitors (SSRI), Melatonin, Duloxetine, Fluoxetine, Imipramine, Nortriptyline or Amitriptyline and other drugs such as Eszopiclone, Escitalopram, Gabapentin, Quiteiapine, Citalopram, Mirtazapine followed by long-acting Melatonin and Ramelteon, also are very useful for the management of various sleep disorders. Hormone replacement therapy presently lacks concrete evidence to be used in menopausal women for sleep disorder. Sleep hygiene practices, self-hypnosis, meditation, and exercise play a very important role.
160Reproductive hormones, aging, and sleep.PubMed
K E Moe
Semin Reprod Endocrinol. 1999;17(4):339-48. doi: 10.1055/s-2007-1016243.
Insomnia, disturbed sleep, and fatigue are among the most frequent health complaints of perimenopausal women. Estrogen replacement therapy (ERT) usually improves sleep, most likely by alleviating vasomotor symptoms. However, sleep difficulties are not restricted to the perimenopausal period. Older postmenopausal women typically experience longer latencies to sleep onset, increased nocturnal waking, increased fragmentation of sleep, and less slow wave (deep) sleep. These sleep changes in older women may be partially related to the postmenopausal profile of sex steroid hormones. Estrogen has powerful effects on several biological factors that directly influence sleep, including body temperature regulation, circadian rhythms, and stress reactivity. The link between sleep disturbance in older women and these CNS effects of estrogen is largely speculative at present. This article reviews what is known, what remains to be addressed, and some clinical implications.
161Menopausal Symptoms and Their Management.PubMed
Nanette Santoro, C Neill Epperson, Sarah B Mathews
Endocrinol Metab Clin North Am. 2015 Sep;44(3):497-515. doi: 10.1016/j.ecl.2015.05.001.
The menopause transition is associated with various symptoms, which can interact to produce morbidity. Vasomotor symptoms are the most commonly reported, but vaginal dryness/dyspareunia, sleep difficulties and adverse mood changes have all been shown to worsen as women approach menopause. For postmenopausal women changes in cognition are more likely to be related to aging and not to hormones. This article reviews the symptoms of hot flashes (vasomotor symptoms), vaginal dryness/dyspareunia, adverse mood, poor sleep/insomnia, and cognitive complaints, describing their epidemiology, diagnosis, and treatment. This article thus reviews the epidemiology, pathophysiology, diagnosis, and treatment of these common menopausal symptoms.
162Sleep During Menopause.PubMed
Helena Hachul, Beatriz Hachul de Campos, Leandro Lucena, et al.
Sleep Med Clin. 2023 Dec;18(4):423-433. doi: 10.1016/j.jsmc.2023.06.004. Epub 2023 Jul 16.
Postmenopause is defined retrospectively after 12 consecutive months of amenorrhea. It represents the end of the reproductive period and ovarian failure. A decrease in estrogen leads to several changes in the short and long term. Among the early changes, vasomotor symptoms (hot flashes) are particularly common, occurring in about 70% of women. In addition, there are changes in mood, anxiety, depression, and insomnia. Insomnia occurs in almost 60% of postmenopausal women. Psychosocial aspects may also affect sleep. Proper diagnosis may lead to adequate treatment of sleep disturbances during menopause. Hormonal or other complementary therapies can improve sleep quality.
163Effects of hormone therapy with estrogen and/or progesterone on sleep pattern in postmenopausal women.PubMed
Helena Hachul, Lia R A Bittencourt, Monica L Andersen, et al.
Int J Gynaecol Obstet. 2008 Dec;103(3):207-12. doi: 10.1016/j.ijgo.2008.07.009. Epub 2008 Sep 23.
OBJECTIVE: To investigate the effects of estrogen and progesterone on sleep in postmenopausal women. METHOD: The 33 participants were randomly assigned to an estrogen or placebo group after undergoing clinical and hormonal assessments and a polysomnogram, and they underwent the same tests again after 12 weeks. Then, while still taking estrogen or placebo, they all received progesterone for another 12 weeks and underwent a final polysomnogram. RESULTS: Estrogen plus progesterone was more effective than estrogen alone in decreasing the prevalence of periodic limb movement (PLM) (8.1% vs 2.8%), hot flashes (14.2% vs 0%), and bruxism (11.1% vs 0%) at night, or somnolence and attention difficulty during the day. The prevalences of breathing irregularities, arousal from sleep, anxiety, and memory impairment were decreased in both groups following progesterone treatment. CONCLUSION: While not significantly affecting sleep quality, hormone therapy decreased the prevalence of arousal in both groups and that of PLM in the group treated with estrogen plus progesterone.
164[Insomnia in the menopause].PubMed
Yu V Shkurenko, A D Ibatov, T D Kapyrina
Zh Nevrol Psikhiatr Im S S Korsakova. 2023;123(9):26-30. doi: 10.17116/jnevro202312309126.
During the menopause transition, pathogenetic changes begin to occur in the reproductive system and they affect the quality of sleep and contribute to the development of insomnia. Given the multifactorial nature of insomnia and the special characteristics of its pathogenesis, it is necessary to adhere to an integrated approach in the treatment of patients of the older age group. In our opinion, if we have indications, a promising direction for the treatment of sleep disorders during period of menopausal syndrome is the use of hormone replacement therapy in addition to traditional methods of the treatment of insomnia.
165Cognitive behavioral therapy for menopausal symptoms.PubMed
M S Hunter
Climacteric. 2021 Feb;24(1):51-56. doi: 10.1080/13697137.2020.1777965. Epub 2020 Jul 6.
This article describes cognitive behavioral therapy (CBT) for women with problematic menopausal symptoms, and provides the evidence from clinical trials of women going through the menopause, women with breast cancer treatment-induced symptoms and women with problematic symptoms in a work context. The CBT focus is primarily on vasomotor symptoms (VMS) but it also targets stress, low mood and sleep problems. CBT is a brief therapy (four to six sessions) that is theory- and evidence-based; it is acceptable to women and effectively reduces the impact of VMS, improves sleep and has benefits to quality of life. VMS frequency is also reduced significantly in some trials but not others. CBT has been found to be consistently effective when delivered in groups, self-help book and on-line formats (with or without additional support). The MENOS 1 and MENOS 2 CBT protocols are recommended for the treatment of VMS by the North American Menopause Society (2015); CBT has been recommended for the treatment of anxiety and depression for women during the menopause transition and post menopause (NICE, 2015); and telephone CBT has been shown to be an effective treatment for insomnia.
166Mind-body therapies for sleep disturbances, depression, and anxiety in menopausal women: a systematic review and meta-analysis of randomized controlled trials.PubMed
Zhixin Fan, Yifan Zhang, Yankai Shu, et al.
Front Public Health. 2025 Nov 18;13:1686981. doi: 10.3389/fpubh.2025.1686981. eCollection 2025.
BACKGROUND: Menopause is frequently accompanied by sleep disturbances, depression, and anxiety, negatively affecting women's quality of life. While hormone therapy can be effective, safety concerns highlight the need for accessible non-pharmacological options. Mind-body therapies (MBTs) have emerged as promising interventions, yet their overall efficacy remains unclear. METHODS: A systematic review and meta-analysis were conducted on randomized controlled trials evaluating the effects of MBTs-such as Yoga, Mindfulness, Qigong, Art therapy, Music therapy, Dance therapy and Reiki-on sleep, depression, and anxiety in perimenopausal and postmenopausal women. Comparator groups included usual care or no-intervention controls. Eighteen studies involving 1,572 participants were identified through PubMed, Embase, Cochrane Library, and Web of Science (through October 10, 2025). Random-effects models were applied, along with subgroup, sensitivity, and publication bias analyses. RESULTS: MBTs significantly improved sleep quality (SMD = -0.86; 95% CI: -1.24 to -0.48), reduced depression (SMD = -0.79; 95% CI: -1.18 to -0.40), and alleviated anxiety (SMD = -1.13; 95% CI: -1.66 to -0.59), showing moderate-to-large effects. Subgroup analyses showed that mindfulness, music therapy, dance therapy, and Reiki yielded greater psychological benefits than yoga and Qigong. Longer interventions (≥12 weeks) and studies from Asia showed stronger effects, possibly due to differences in intervention type, cultural familiarity, or adherence. Sensitivity analyses confirmed robust results, and no publication bias was detected. CONCLUSION: MBTs offer moderate-to-large benefits and represent safe, low-risk strategies for managing menopausal symptoms. Expressive approaches, including Mindfulness, Music therapy, and Dance therapy, may provide added value for emotional regulation and psychological well-being. Yoga and Qigong provide stable benefits for sleep improvement. High-quality trials are needed to inform clinical guidelines. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420251103844.
167Improving sleep quality interventions among menopausal women with sleep disturbances in Taiwan: a preliminary study.PubMed
Hsiu-Chin Hsu, Lee-Ing Tsao, Mei-Hsiang Lin
Appl Nurs Res. 2015 Nov;28(4):374-80. doi: 10.1016/j.apnr.2015.01.004. Epub 2015 Feb 26.
AIM: The aim of this study was to evaluate the effectiveness of improving sleep quality interventions in menopausal women with sleep disturbance. BACKGROUND: Sleep disturbances are an extensive and common problem among menopausal women. There is an increased trend in the use of non-pharmacological methods to alleviate sleep disturbances. Studies that have implemented two or more non-pharmacological strategies for menopausal women are scant. METHODS: A repeat measurement with a randomized assignment was conducted. A total of 59 menopausal women with sleep disturbance were recruited and randomly assigned to experimental (n = 29) and control (n = 30) groups. Participants in the experimental group received four 2-hour improving sleep quality activities, whereas the control group received regular greeting calls. Sleep quality was measured prior to intervention, and on the 5th and 8th weeks by using the Pittsburg's Sleep Quality Index, and Actiwatch was worn before and during the 8 weeks of intervention. Generalized estimating equation was used to analyze data. RESULTS: The results revealed that subjective sleep quality had significant main effect in group and time. The findings of the objective measurement showed that participants in the experimental group had significantly shorter frequency of awakening time and increased sleep efficiency. CONCLUSION: The improving sleep quality intervention is a healthy and cost-effective method to improve sleep quality in community-dwelling menopausal women with sleep disturbance.
168Effectiveness of Acupuncture and Acupressure for Improving the Sleep Quality of Menopausal Women: A Meta-Analysis.PubMed
Leila Eskandari, Afsaneh Keramat, Marzieh Rohani-Rasaf
Iran J Med Sci. 2025 Mar 1;50(3):132-145. doi: 10.30476/ijms.2024.102726.3586. eCollection 2025 Mar.
BACKGROUND: Various pharmacological and non-pharmacological treatments are utilized to address sleep disorders. This meta-analysis aimed to evaluate the effects of acupuncture and acupressure on enhancing sleep quality in menopausal women. METHODS: A systematic search was conducted using multiple databases, including Scopus, MEDLINE/PubMed, Cochrane CENTRAL, ProQuest, Google Scholar, and Iranian databases (SID, Iranmedex, Magiran) with no date restrictions up to July 2024. Studies published in both Persian and English were included in this meta-analysis. The search utilized keywords such as acupuncture, acupressure, sleep quality, insomnia, menopause, and sleep disorders. A pairwise random-effects meta-analysis was performed to calculate the mean difference (MD) and 95% confidence intervals (95% CIs). RESULTS: The analyses indicated that both acupuncture and acupressure effectively improved sleep quality in menopausal women. Eight trials with 499 participants demonstrated that acupressure significantly enhanced sleep quality (MD=-2.33, 95% CI=-3.27 to -1.38; I=94%, P<0.001, n=8). Additionally, six trials with 344 participants showed that acupuncture enhanced sleep quality (MD=-3.47, 95% CI=-5.06 to -1.88; I=97%, P<0.001, n=6). CONCLUSION: The findings revealed that acupressure and acupuncture might improve sleep quality in menopausal women. However, there was a high heterogeneity between studies, and further research is required to confirm the findings of the present study.
169Recent Advancements in Treating Sleep Disorders in Co-Occurring PTSD.PubMed
Peter J Colvonen, Laura D Straus, Carl Stepnowsky, et al.
Curr Psychiatry Rep. 2018 Jun 21;20(7):48. doi: 10.1007/s11920-018-0916-9.
PURPOSE OF REVIEW: Comorbidity of posttraumatic stress disorder (PTSD) and insomnia, nightmares, and obstructive sleep apnea (OSA) is high. We review recent research on psychotherapeutic and pharmacological interventions for sleep disorders in PTSD. RECENT FINDINGS: PTSD treatments decrease PTSD severity and nightmare frequency, but do not resolve OSA or insomnia. Research on whether insomnia hinders PTSD treatment shows mixed results; untreated OSA does interfere with PTSD treatment. Cognitive behavioral therapy for insomnia is the recommended treatment for insomnia; however, optimal ordering with PTSD treatment is unclear. PTSD treatment may be most useful for PTSD-related nightmares. CPAP therapy is recommended for OSA but adherence can be low. Targeted treatment of sleep disorders in the context of PTSD offers a unique and underutilized opportunity to advance clinical care and research. Research is needed to create screening protocols, determine optimal order of treatment, and elucidate mechanisms between sleep and PTSD treatments.
170Delivering Cognitive Behavioral Therapy for Insomnia in Military Personnel and Veterans.PubMed
Monica R Kelly, Ruth Robbins, Jennifer L Martin
Sleep Med Clin. 2019 Jun;14(2):199-208. doi: 10.1016/j.jsmc.2019.01.003. Epub 2019 Mar 29.
Insomnia is commonly reported by military populations, especially those with comorbid mental and physical health conditions. Co-occurring conditions result in an altered presentation of insomnia symptoms, and complicate provision of cognitive-behavioral therapy for insomnia (CBT-I), requiring supplementary assessment or modifications to traditional techniques. CBT-I has consistently demonstrated positive outcomes for active-duty service members and veterans, even in the context of significant comorbidities such as post-traumatic stress disorder, depression, sleep apnea, and chronic pain. Despite its promise, studies of CBT-I in some populations, including women and individuals with substance use disorders, remain relatively understudied in active-duty and veteran populations.
171Associations between insomnia and cardiovascular diseases: a meta-review and meta-analysis of observational and Mendelian randomization studies.PubMed
Xuejiao Zhang, Yujing Sun, Shuo Ye, et al.
J Clin Sleep Med. 2024 Dec 1;20(12):1975-1984. doi: 10.5664/jcsm.11326.
STUDY OBJECTIVES: Observational studies suggest associations between insomnia and cardiovascular diseases (CVDs), but the causal mechanism remains unclear. We investigated the potential causal associations between insomnia and CVDs by a combined systematic meta-review and meta-analysis of observational and Mendelian randomization studies. METHODS: We searched PubMed, Web of Science, and Embase for English-language articles from inception to July 11, 2023. Two reviewers independently screened the articles to minimize potential bias. We summarized the current evidence on the associations of insomnia with coronary artery disease, atrial fibrillation, heart failure, myocardial infarction, hypertension, and stroke risk by combining meta-analyses of observational and Mendelian randomization studies. RESULTS: Four meta-analyses of observational studies and 9 Mendelian randomization studies were included in the final data analysis. A systematic meta-review of observational studies provided strong evidence that insomnia is an independent risk factor for many CVDs, including atrial fibrillation, myocardial infarction, and hypertension. A meta-analysis of Mendelian randomization studies revealed that insomnia may be potentially causally related to coronary artery disease (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.10-1.19, I = 97%), atrial fibrillation (OR = 1.02, 95% CI = 1.01-1.04, I = 94%), heart failure (OR = 1.04, 95% CI = 1.03-1.06, I =97%), hypertension (OR = 1.16, 95% CI = 1.13-1.18, I = 28%), large artery stroke (OR = 1.14, 95% CI = 1.05-1.24, I = 0%), any ischemic stroke (OR = 1.09, 95% CI = 1.03-1.14, I = 60%), and primary intracranial hemorrhage (OR = 1.16, 95% CI = 1.05-1.27, I = 0%). No evidence suggested that insomnia is causally associated with cardioembolic or small vessel stroke. CONCLUSIONS: Our results provide strong evidence supporting a possible causal association between insomnia and CVD risk. Strategies to treat insomnia may be promising targets for preventing CVDs. CITATION: Zhang X, Sun Y, Ye S, et al. Associations between insomnia and cardiovascular diseases: a meta-review and meta-analysis of observational and Mendelian randomization studies. 2024;20(12):1975-1984.
172Psychotherapeutic and pharmacological agents for post-traumatic stress disorder with sleep disorder: network meta-analysis.PubMed
Cheng-Yang Huang, Yi-Fan Zhao, Zhi-Xin Zhang, et al.
Ann Med. 2024 Dec;56(1):2381696. doi: 10.1080/07853890.2024.2381696. Epub 2024 Jul 26.
OBJECTIVE: The current guidelines and canonical norms of diagnosis or treatment for Post-traumatic stress disorder (PTSD) with sleep disorder are still conflicting and have not yet reached a consensus. This study aimed to unravel the most effective countermeasures between two categories (psychotherapy and pharmacotherapy) put forward by the National Institute for Health and Clinical Excellence (NICE) and World Federation of Societies of Biological Psychiatry (WFSBP) respectively to treat PTSD individuals co-exist with sleep disorders. METHODS: Four databases, including PubMed, EMBASE, Cochrane Library, and APA PsyNet, were searched from inception to February 02, 2023. RESULTS: Twenty articles with 24 Randomized controlled trials (RCTs) and a total number of 1,647 participants were included. As demonstrated in the network meta-analysis comparison results, CBT-I (standardized mean differences (SMD) = -1.51,95% confidence interval (CI):-2.55 to -0.47), CBT-I IRT (SMD = -1.71, 95%CI:-3.39, -0.03), prazosin (SMD = -0.87,95%CI:-1.59 to -0.16) and hydroxyzine (SMD = -1.06, 95%CI: -1.94 to -0.19) significantly reduced PTSD symptoms compared with placebo. In contrast to placebo, CBT-I (SMD = -5.61,95%CI:-8.82 to -2.40) significantly improved sleep quality. For nightmare severity, IRT (SMD =-0.65, 95%CI:-1.00 to -0.31), prazosin (SMD = -1.20,95%CI:-1.72 to -0.67) and hydroxyzine (SMD = -0.98,95%CI:-1.58 to -0.37) significantly reduced nightmare severity in comparison with placebo. CONCLUSIONS: This study suggested that under most circumstances, psychotherapy namely CBT-I had a favorable profile, but pharmacotherapy with prazosin was effective in managing nightmare severity. The sole avail of CBT-I was recommended to improving sleep quality while CBT-I and CBT-I plus IRT showed excellent management of PTSD symptom severity. Exposure to CBT-I isrecommended for depression. The relevant clinical guidelines for the management of individuals with PTSD and sleep disorders may regard this as a reference. PROSPERO: CRD42023415240.
173Piloting cognitive-behavioral therapy for insomnia integrated with prolonged exposure.PubMed
Peter J Colvonen, Sean P A Drummond, Abigail C Angkaw, et al.
Psychol Trauma. 2019 Jan;11(1):107-113. doi: 10.1037/tra0000402. Epub 2018 Sep 13.
OBJECTIVE: Approximately 35-61% of individuals with posttraumatic stress disorder (PTSD) report insomnia. Further, upward of 70% report clinically significant insomnia following PTSD treatment. There are converging lines of evidence suggesting that insomnia not only independently affects daytime functioning and worsens PTSD symptoms but also may compromise response to PTSD treatment, such as prolonged exposure (PE). Taken together, integrated insomnia and PTSD treatment may increase client-centered care and treatment outcomes. METHOD: This article reviews the theory and evidence for treating sleep prior to PTSD treatment, describes the key elements of integrated cognitive-behavioral treatment for insomnia (CBT-I) and PE (2NITE protocol), and presents pilot data from a sample of 12 treatment-seeking veterans with PTSD and insomnia who completed the 2NITE protocol. Sleep data were collected with sleep diaries and actigraphy watches. RESULTS: The Client Satisfaction Questionnaire indicated high satisfaction with the 2NITE protocol (mean score 29.66 out of 32 points). On average, there were statistical and clinically significant changes in all measures, including a 20.17-point decrease in the PTSD Checklist DSM-5, a 11.75-point decrease in the insomnia severity index, an 18.58-point increase in the World Health Organization Quality of Life index, a 11% increase in sleep efficiency, and a 51-min increase in total sleep time from the actigraphy data. CONCLUSIONS: Among individuals with insomnia and PTSD, integrating CBT-I and PE with the 2NITE protocol represents a logical, innovative, and empirically informed method for augmenting existing treatments and optimizing outcomes that justifies further investigation. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
174Posttraumatic Stress Disorder and Sleep.PubMed
Wilfred R Pigeon, Autumn M Gallegos
Sleep Med Clin. 2015 Mar;10(1):41-8. doi: 10.1016/j.jsmc.2014.11.010. Epub 2014 Dec 15.
The purpose of this article is to provide a brief overview of sleep in the context of posttraumatic stress disorder (PTSD) and focus on the treatment of the most common sleep disorders encountered by patients with PTSD: insomnia and nightmares. The effects of the standard treatments for PTSD are discussed along with a review of available treatments for insomnia and nightmares. Particular emphasis is placed on nonpharmacologic treatments for these sleep disorders and how they may be adapted for delivery to patients with PTSD.
175Impact of Traumatic Stress on Sleep and Management Options in Women.PubMed
Ihori Kobayashi, Mary Katherine Howell
Sleep Med Clin. 2018 Sep;13(3):419-431. doi: 10.1016/j.jsmc.2018.04.009. Epub 2018 Jun 28.
After exposure to traumatic stress, women are at greater risk than men for developing symptoms of some psychiatric disorders, including insomnia and nightmares. Sleep disturbance is one of the most refractory symptoms of posttraumatic stress disorder. Women were included in a few studies that examined efficacy of psychological or pharmacologic interventions for trauma-related sleep disturbances. Studies demonstrated preliminary evidence for efficacy of cognitive behavioral therapy for insomnia, imagery rehearsal therapy, and combinations of these techniques in treating insomnia and nightmares in trauma-exposed women. Prazosin as an adjunct to ongoing treatment is a potentially efficacious strategy for treating trauma-related nightmares in women.
176Posttraumatic Stress Disorder and Anxiety-Related Conditions.PubMed
John B Williamson, Michael S Jaffee, Ricardo E Jorge
Continuum (Minneap Minn). 2021 Dec 1;27(6):1738-1763. doi: 10.1212/CON.0000000000001054.
PURPOSE OF REVIEW: This article provides a synopsis of current assessment and treatment considerations for posttraumatic stress disorder (PTSD) and related anxiety disorder characteristics. Epidemiologic and neurobiological data are reviewed as well as common associated symptoms, including sleep disruption, and treatment approaches to these conditions. RECENT FINDINGS: PTSD is no longer considered an anxiety-related disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition classification and instead is associated with trauma/stressor-related disorders. PTSD symptoms are clustered into four domains including intrusive experiences, avoidance, mood, and arousal symptoms. Despite this reclassification, similarities exist in consideration of diagnosis, treatment, and comorbidities with anxiety disorders. PTSD and anxiety-related disorders are heterogeneous, which is reflected by the neural circuits involved in the genesis of symptoms that may vary across symptom domains. Treatment is likely to benefit from consideration of this heterogeneity.Research in animal models of fear and anxiety, as well as in humans, suggests that patients with PTSD and generalized anxiety disorder have difficulty accurately determining safety from danger and struggle to suppress fear in the presence of safety cues.Empirically supported psychotherapies commonly involved exposure (fear extinction learning) and are recommended for PTSD. Cognitive-behavioral therapy has been shown to be effective in other anxiety-related disorders. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are commonly used in the treatment of PTSD and anxiety disorders in which pharmacologic intervention is supported. Treating sleep disruption including sleep apnea (continuous positive airway pressure [CPAP]), nightmares, and insomnia (preferably via psychotherapy) may improve symptoms of PTSD, as well as improve mood in anxiety disorders. SUMMARY: PTSD has a lifetime prevalence that is close to 10% and shares neurobiological features with anxiety disorders. Anxiety disorders are the most common class of mental conditions and are highly comorbid with other disorders; treatment considerations typically include cognitive-behavioral therapy and pharmacologic intervention. Developing technologies show some promise as treatment alternatives in the future.
177Hypnotic use and the risk of cardiovascular diseases in insomnia patients.PubMed
Yao Xie, Shiyu Zhu, Shuang Wu, et al.
Eur J Prev Cardiol. 2025 Apr 22;32(6):466-474. doi: 10.1093/eurjpc/zwae263.
AIMS: We aimed to examine the association between hypnotic agents and cardiovascular outcomes in general individuals with insomnia. METHODS AND RESULTS: In a propensity score matched cohort of UK Biobank (UKB) participants with insomnia, Cox proportional hazard model was used to estimate the association between regular use of hypnotic agents and predetermined cardiovascular outcomes including incident coronary heart diseases (CHD), heart failure (HF), stroke, and cardiovascular death. Inverse probability of treatment weighting, competing risk models, and shared frailty models were further performed during sensitivity analysis. Drug-target Mendelian randomization (MR) analyses were employed for further evaluation of the association between therapeutic targets of hypnotics and cardiovascular diseases. During a median follow-up of 14.3 years, the matched cohort documented a total of 929 CHD cases, 360 HF cases, 262 stroke cases, and 180 cardiovascular deaths. No significant association was detected between Z-meds and CHD, stroke, and cardiovascular mortality. Benzodiazepine use was significantly associated with the increased risk of CHD, HF, and cardiovascular mortality. The inverse probability of treatment weighting, competing risk models, and shared frailty models didn't alter the above associations. Moreover, drug-target MR analyses corroborated the safety of Z-meds in the general population regarding cardiovascular health. CONCLUSION: Our findings suggested the heterogeneous associations between different categories of hypnotics and incident cardiovascular events in individuals with insomnia. Both observational and genetic evidence raised safety concerns regarding the cardiovascular impact of benzodiazepines. No cardiovascular hazard of Z-meds was discovered in the UKB population with insomnia.
178Sleep disorders in chronic kidney disease.PubMed
Owen D Lyons
Nat Rev Nephrol. 2024 Oct;20(10):690-700. doi: 10.1038/s41581-024-00848-8. Epub 2024 May 24.
Sleep disorders are highly prevalent in chronic kidney disease (CKD) but are often under-recognized. Restless legs syndrome, which is common in CKD owing to issues with dopamine metabolism and is exacerbated by iron deficiency and uraemia, can lead to poor sleep quality and increased daytime fatigue. Insomnia is also prevalent in CKD, particularly in patients requiring dialysis, with increased sleep latency and sleep fragmentation being reported. The cause of insomnia in CKD is multifactorial - poor sleep habits and frequent napping during dialysis, uraemia, medications and mood disorders have all been suggested as potential contributing factors. Sleep apnoea and CKD are also now recognized as having a bi-directional relationship. Sleep apnoea is a risk factor for accelerated progression of CKD, and fluid overload, which is associated with kidney failure, can lead to both obstructive and central sleep apnoea. The presence of obstructive sleep apnoea in CKD can exacerbate the already heightened cardiovascular morbidity and mortality in these patients, as well as leading to daytime fatigue and reduced quality of life. Increased awareness, timely diagnosis and appropriate therapeutic interventions are essential to reduce the negative impact of sleep disorders in patients with kidney disease.