Krystal Andrew D, Mittoux Aurélia, Meisels Peter, Baker Ross A
Duke University Hospital, Durham, NC 27710.
Duke University Hospital, Durham, North Carolina, USA.
Prim Care Companion CNS Disord. 2016 Sep 8;18(5). doi: 10.4088/PCC.15m01914.
Brexpiprazole is a serotonin-dopamine activity modulator. We evaluated the effects of adjunctive treatment with brexpiprazole on sleep disturbances in patients with DSM-IV-TR major depressive disorder (MDD) and inadequate response to antidepressant treatment.
This study was conducted between September 27, 2013, and August 19, 2014. Patients with inadequate response to antidepressant treatment and sleep disturbances continued treatment with their current antidepressant for 2 weeks. Patients still having inadequate response and sleep efficiency less than 85% measured by baseline polysomnography (PSG) received 8-week open-label treatment with their current antidepressant treatment and adjunctive brexpiprazole (target dose: 3 mg/d). Assessments included PSG recordings and scales of insomnia severity, depressive symptoms, and daytime alertness and functioning. Changes from baseline to week 8 were analyzed.
Forty-four patients were treated. Improvements (P < .05) measured by PSG and Consensus Sleep Diary for Morning, respectively, were observed in sleep efficiency (10.4 and 15.4 percentage points), total sleep time (49.0 and 84.5 min), sleep onset latency (-19.7 and -42.6 min), wake-time after sleep onset (-26.4 and -48.0 min), and latency to persistent sleep (-24.9 min, PSG only). Insomnia Severity Index (ISI) total score was improved (-9.2), as was daytime sleepiness (-2.1) as measured by the Epworth Sleepiness Scale (ESS) total score and morning sleepiness (-9.2) as measured by the Bond-Lader Visual Analog Scale (all P < .05). Reaction time was slightly decreased (-0.2 sec-1) by treatment (P < .05). Depressive symptoms improved (Montgomery-Asberg Depression Rating Scale [MADRS]: -16.0 and Clinical Global Impressions-Severity [CGI-S]: -1.8), as did functioning (-8.4) assessed by the Massachusetts General Hospital-Cognitive and Physical Functioning Questionnaire (all P < .05). Improvements in depressive symptoms were dependent on sleep (as assessed by ISI) (P < .0001) and improvements in daytime alertness (as assessed by ESS) were dependent on improvements in ISI (P = .009). No new safety concerns were observed compared to previous brexpiprazole studies.
In patients with inadequate response to antidepressant treatment and sleep disturbances treated with adjunctive brexpiprazole, physiologic measures of sleep and daytime alertness were improved.
ClinicalTrials.gov identifier: NCT01942733.
布雷哌唑是一种5-羟色胺-多巴胺活性调节剂。我们评估了布雷哌唑辅助治疗对符合《精神疾病诊断与统计手册》第四版修订版（DSM-IV-TR）的重度抑郁症（MDD）患者且对抗抑郁治疗反应不足的睡眠障碍的影响。
本研究于2013年9月27日至2014年8月19日进行。对抗抑郁治疗反应不足且有睡眠障碍的患者继续使用当前的抗抑郁药物治疗2周。对抗抑郁治疗仍反应不足且通过基线多导睡眠图（PSG）测量睡眠效率低于85%的患者，接受为期8周的开放标签治疗，使用当前的抗抑郁药物治疗并联合布雷哌唑（目标剂量：3毫克/天）。评估包括PSG记录以及失眠严重程度、抑郁症状、日间警觉性和功能的量表。分析从基线到第8周的变化。
44例患者接受了治疗。通过PSG和《早晨共识睡眠日记》测量，分别在睡眠效率（10.4和15.4个百分点）、总睡眠时间（49.0和84.5分钟）、入睡潜伏期（-19.7和-42.6分钟）、睡眠后觉醒时间（-26.4和-48.0分钟）以及持续睡眠潜伏期（-24.9分钟，仅PSG测量）方面观察到改善（P < 0.05）。失眠严重程度指数（ISI）总分有所改善（-9.2），通过爱泼沃斯思睡量表（ESS）总分测量的日间嗜睡程度（-2.1）以及通过邦德-莱德视觉模拟量表测量的早晨嗜睡程度（-9.2）也有所改善（均P < 0.05）。治疗使反应时间略有缩短（-0.2秒-1）（P < 0.05）。抑郁症状有所改善（蒙哥马利-阿斯伯格抑郁评定量表[MADRS]：-16.0和临床总体印象-严重程度[CGI-S]：-1.8），通过麻省总医院认知与身体功能问卷评估的功能也有所改善（-8.4）（均P < 0.05）。抑郁症状的改善取决于睡眠（通过ISI评估）（P < 0.0001），日间警觉性的改善（通过ESS评估）取决于ISI的改善（P = 0.009）。与之前的布雷哌唑研究相比，未观察到新的安全问题。
在对抗抑郁治疗反应不足且有睡眠障碍并接受布雷哌唑辅助治疗的患者中，睡眠和日间警觉性的生理指标得到了改善。
ClinicalTrials.gov标识符：NCT01942733。
