Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing.
J Clin Psychiatry. 2015 Apr;76(4):e487-98. doi: 10.4088/JCP.14r09204.
To comparatively analyze the efficacy, acceptability, and tolerability of various augmentation agents in adult patients with treatment-resistant depression.
An electronic literature search of PubMed, EMBASE, the Cochrane Library, Web of Science, EBSCO, PsycINFO, EAGLE, and NTIS for trials published up to December 2013 was conducted. Several clinical trial registry agencies and US Food and Drug Administration reports were also reviewed. No language, publication date, or publication status restrictions were imposed.
Randomized controlled trials comparing 11 augmentation agents (aripiprazole, bupropion, buspirone, lamotrigine, lithium, methylphenidate, olanzapine, pindolol, quetiapine, risperidone, and thyroid hormone) with each other and with placebo for adult treatment-resistant depression were included.
The proportion of patients who responded to treatment was defined as primary efficacy, and the proportion of all-cause discontinuation and side-effects discontinuation were respectively defined as acceptability and tolerability, which were assessed with odds ratios (ORs) and a Bayesian random-effects model with 95% credible intervals (CrIs).
A total of 48 trials consisting of 6,654 participants were eligible. In terms of the primary efficacy, quetiapine (OR = 1.92; 95% CrI, 1.39-3.13), aripiprazole (OR = 1.85; 95% CrI, 1.27-2.27), thyroid hormone (OR = 1.84; 95% CrI, 1.06-3.56), and lithium (OR = 1.56; 95% CrI, 1.05-2.55) were significantly more effective than placebo. Sensitivity analyses indicated that efficacy estimates for aripiprazole and quetiapine were more robust than those for thyroid hormone and lithium. In terms of acceptability, no significant difference was found between active agents and placebo. In terms of tolerability, compared to placebo, quetiapine (OR = 3.85; 95% CrI, 1.92-8.33), olanzapine (OR = 3.36; 95% CrI, 1.60-8.61), aripiprazole (OR = 2.51; 95% CrI, 1.11-7.69), and lithium (OR = 2.30; 95% CrI, 1.04-6.03) were significantly less well tolerated.
Quetiapine and aripiprazole appear to be the most robust evidence-based options for augmentation therapy in patients with treatment-resistant depression, but clinicians should interpret these findings cautiously in light of the evidence of potential treatment-related side effects.
比较分析各种增效剂在治疗抵抗性抑郁症成年患者中的疗效、可接受性和耐受性。
对截至 2013 年 12 月发表的文献进行了电子检索，包括 PubMed、EMBASE、Cochrane 图书馆、Web of Science、EBSCO、PsycINFO、EAGLE 和 NTIS。还查阅了几个临床试验注册机构和美国食品和药物管理局的报告。没有对语言、出版日期或出版状态进行限制。
纳入了将 11 种增效剂（阿立哌唑、安非他酮、丁螺环酮、拉莫三嗪、锂、哌甲酯、奥氮平、普萘洛尔、喹硫平、利培酮和甲状腺激素）与其他增效剂和安慰剂进行比较的随机对照试验。
将治疗反应的患者比例定义为主要疗效，将所有原因停药和副作用停药的比例分别定义为可接受性和耐受性，并用优势比（ORs）和贝叶斯随机效应模型进行评估，置信区间（CrIs）为 95%。
共有 48 项试验，包括 6654 名参与者符合条件。就主要疗效而言，喹硫平（OR=1.92；95%CrI，1.39-3.13）、阿立哌唑（OR=1.85；95%CrI，1.27-2.27）、甲状腺激素（OR=1.84；95%CrI，1.06-3.56）和锂（OR=1.56；95%CrI，1.05-2.55）明显优于安慰剂。敏感性分析表明，阿立哌唑和喹硫平的疗效估计比甲状腺激素和锂更可靠。在可接受性方面，活性药物与安慰剂之间无显著差异。在耐受性方面，与安慰剂相比，喹硫平（OR=3.85；95%CrI，1.92-8.33）、奥氮平（OR=3.36；95%CrI，1.60-8.61）、阿立哌唑（OR=2.51；95%CrI，1.11-7.69）和锂（OR=2.30；95%CrI，1.04-6.03）的耐受性明显较差。
喹硫平和阿立哌唑似乎是治疗抵抗性抑郁症患者增效治疗最有力的循证选择，但鉴于潜在治疗相关副作用的证据，临床医生应谨慎解释这些发现。
