阿立哌唑辅助治疗重度抑郁症的安全性和耐受性：一项汇总的事后分析（研究CN138 - 139和CN138 - 163）
Safety and Tolerability of Adjunctive Aripiprazole in Major Depressive Disorder: A Pooled Post Hoc Analysis (studies CN138-139 and CN138-163).
作者信息
Nelson J Craig, Thase Michael E, Trivedi Madhukar H, Fava Maurizio, Han Jian, Van Tran Quynh, Pikalov Andrei, Qi Ying, Carlson Berit X, Marcus Ronald N, Berman Robert M
机构信息
Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA.
出版信息
Prim Care Companion J Clin Psychiatry. 2009;11(6):344-52. doi: 10.4088/PCC.08m00744gre.
OBJECTIVE
To evaluate the safety and tolerability of aripiprazole adjunctive to standard antidepressant therapy (ADT) for patients with major depressive disorder (DSM-IV-TR criteria).
METHOD
Data from 2 identical studies of aripiprazole augmentation (8 weeks of prospective ADT treatment followed by 6 weeks of randomized double-blind adjunctive treatment) were pooled. The incidence of treatment-emergent adverse events (TEAEs) and weight, electrocardiogram (ECG), and laboratory measurements were assessed during the 6-week phase, including time course, severity, resolution, and predictors. The studies were conducted from June 2004 to April 2006 and September 2004 to December 2006.
RESULTS
The safety analysis included 737 outpatients (aripiprazole, n = 371; placebo, n = 366). The majority of patients completed the trials (aripiprazole, 86%; placebo, 88%). Common TEAEs (≥ 5% and twice the placebo rate) with aripiprazole were akathisia (25%), restlessness (12%), insomnia (8%), fatigue (8%), blurred vision (6%), and constipation (5%). Most TEAEs were of mild to moderate severity (aripiprazole, 89%; placebo, 95%). TEAE rates in the aripiprazole and placebo groups were not affected by ADT, age, or gender. Discontinuation due to TEAEs was low (aripiprazole, 3%; placebo, 1%). Mean weight change was higher with aripiprazole versus placebo (1.73 kg vs 0.38 kg, P < .001). At endpoint, clinical laboratory parameters, vital signs, and ECG indices (including QT(c) interval) were similar between groups. Akathisia with aripiprazole generally occurred in the first 3 weeks (76%), was of mild to moderate severity (92%), and led to discontinuation in 3 patients (0.8%). Within the aripiprazole group, age (18-40 years) was the only positive predictor for akathisia.
CONCLUSIONS
In this short-term post hoc analysis, aripiprazole as augmentation to ADT demonstrated a safety and tolerability profile similar to that in monotherapy studies in other psychiatric populations. Controlled long-term safety and efficacy data of aripiprazole as adjunctive to ADT are warranted.
TRIAL REGISTRATION
clinicaltrials.gov Identifiers: NCT00095823 (CN138-139) and NCT00095758 (CN138-163).
目的
评估阿立哌唑辅助标准抗抑郁治疗（ADT）用于重度抑郁症（符合《精神疾病诊断与统计手册第四版，修订版》标准）患者的安全性和耐受性。
方法
汇总两项关于阿立哌唑增效治疗的相同研究的数据（先进行8周前瞻性ADT治疗，随后进行6周随机双盲辅助治疗）。在6周阶段评估治疗中出现的不良事件（TEAE）的发生率以及体重、心电图（ECG）和实验室指标，包括时间进程、严重程度、缓解情况和预测因素。研究分别于2004年6月至2006年4月以及2004年9月至2006年12月进行。
结果
安全性分析纳入737例门诊患者（阿立哌唑组，n = 371；安慰剂组，n = 366）。大多数患者完成了试验（阿立哌唑组，86%；安慰剂组，88%）。阿立哌唑组常见的TEAE（≥5%且为安慰剂组发生率的两倍）有静坐不能（25%）、烦躁不安（12%）、失眠（8%）、疲劳（8%）、视力模糊（6%）和便秘（5%）。大多数TEAE为轻度至中度严重程度（阿立哌唑组，89%；安慰剂组，95%）。阿立哌唑组和安慰剂组的TEAE发生率不受ADT、年龄或性别的影响。因TEAE而停药的比例较低（阿立哌唑组，3%；安慰剂组，1%）。与安慰剂相比，阿立哌唑组的平均体重变化更大（1.73 kg对0.38 kg，P <.001）。在研究终点，两组间临床实验室参数、生命体征和ECG指标（包括QT(c)间期）相似。阿立哌唑所致静坐不能一般发生在最初3周（76%），为轻度至中度严重程度（92%），导致3例患者停药（0.8%）。在阿立哌唑组内，年龄（18 - 40岁）是静坐不能的唯一阳性预测因素。
结论
在这项短期事后分析中，阿立哌唑辅助ADT治疗的安全性和耐受性与其他精神疾病人群的单药治疗研究相似。需要阿立哌唑辅助ADT治疗的对照长期安全性和疗效数据。
试验注册
clinicaltrials.gov标识符：NCT00095823（CN138 - 139）和NCT00095758（CN138 - 163）。
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