RAND Health, Southern California Evidence-Based Practice Center, 1776 Main St, Santa Monica, CA 90401, USA.
JAMA. 2011 Sep 28;306(12):1359-69. doi: 10.1001/jama.2011.1360.
Atypical antipsychotic medications are commonly used for off-label conditions such as agitation in dementia, anxiety, and obsessive-compulsive disorder.
To perform a systematic review on the efficacy and safety of atypical antipsychotic medications for use in conditions lacking approval for labeling and marketing by the US Food and Drug Administration.
Relevant studies published in the English language were identified by searches of 6 databases (PubMed, EMBASE, CINAHL, PsycInfo, Cochrane DARE, and CENTRAL) from inception through May 2011. Controlled trials comparing an atypical antipsychotic medication (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, asenapine, iloperidone, or paliperidone) with placebo, another atypical antipsychotic medication, or other pharmacotherapy for adult off-label conditions were included. Observational studies with sample sizes of greater than 1000 patients were included to assess adverse events.
Independent article review and study quality assessment by 2 investigators.
Of 12 228 citations identified, 162 contributed data to the efficacy review. Among 14 placebo-controlled trials of elderly patients with dementia reporting a total global outcome score that includes symptoms such as psychosis, mood alterations, and aggression, small but statistically significant effects sizes ranging from 0.12 and 0.20 were observed for aripiprazole, olanzapine, and risperidone. For generalized anxiety disorder, a pooled analysis of 3 trials showed that quetiapine was associated with a 26% greater likelihood of a favorable response (defined as at least 50% improvement on the Hamilton Anxiety Scale) compared with placebo. For obsessive-compulsive disorder, risperidone was associated with a 3.9-fold greater likelihood of a favorable response (defined as a 25% improvement on the Yale-Brown Obsessive Compulsive Scale) compared with placebo. In elderly patients, adverse events included an increased risk of death (number needed to harm [NNH] = 87), stroke (NNH = 53 for risperidone), extrapyramidal symptoms (NNH = 10 for olanzapine; NNH = 20 for risperidone), and urinary tract symptoms (NNH range = 16-36). In nonelderly adults, adverse events included weight gain (particularly with olanzapine), fatigue, sedation, akathisia (for aripiprazole), and extrapyramidal symptoms.
Benefits and harms vary among atypical antipsychotic medications for off-label use. For global behavioral symptom scores associated with dementia in elderly patients, small but statistically significant benefits were observed for aripiprazole, olanzapine, and risperidone. Quetiapine was associated with benefits in the treatment of generalized anxiety disorder, and risperidone was associated with benefits in the treatment of obsessive-compulsive disorder; however, adverse events were common.
非典型抗精神病药物通常用于痴呆症、焦虑症和强迫症等未经批准的适应症。
对未经美国食品和药物管理局批准的标签和市场营销的适应症使用非典型抗精神病药物的疗效和安全性进行系统评价。
从 2011 年 5 月开始，通过 6 个数据库（PubMed、EMBASE、CINAHL、PsycInfo、Cochrane DARE 和 CENTRAL）检索了发表在英文文献中的相关研究。纳入了比较非典型抗精神病药物（利培酮、奥氮平、喹硫平、阿立哌唑、齐拉西酮、阿塞那平、依匹哌唑或帕利哌酮）与安慰剂、另一种非典型抗精神病药物或其他药物治疗成人未经批准适应症的对照试验。纳入了样本量大于 1000 例的观察性研究，以评估不良反应。
两名研究者独立进行文章评价和研究质量评估。
在 12228 篇引文的基础上，有 162 篇提供了疗效评价的数据。在 14 项针对痴呆老年患者的安慰剂对照试验中，总全球结局评分包括精神病、情绪改变和攻击等症状，阿立哌唑、奥氮平和利培酮观察到的疗效大小为 0.12 至 0.20，具有统计学意义。对于广泛性焦虑症，3 项试验的汇总分析显示，与安慰剂相比，喹硫平与更好的反应（定义为汉密尔顿焦虑量表至少改善 50%）的可能性增加了 26%。对于强迫症，与安慰剂相比，利培酮与更好反应的可能性增加了 3.9 倍（耶鲁布朗强迫症量表改善 25%）。在老年患者中，不良反应包括死亡风险增加（危害比[NNH] = 87）、中风（利培酮 NNH = 53）、锥体外系症状（奥氮平 NNH = 10；利培酮 NNH = 20）和尿路感染症状（NNH 范围= 16-36）。在非老年成年人中，不良反应包括体重增加（尤其是奥氮平）、疲劳、镇静、静坐不能（阿立哌唑）和锥体外系症状。
非典型抗精神病药物在未经批准的用途中具有不同的益处和危害。对于与老年痴呆症相关的总行为症状评分，阿立哌唑、奥氮平和利培酮观察到的疗效具有统计学意义但较小。喹硫平与广泛性焦虑症的治疗益处相关，利培酮与强迫症的治疗益处相关；然而，不良反应很常见。
