Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada; British Columbia Centre for Substance Use, Vancouver, British Columbia, Canada.
Department of Neurology, University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine, Queen's University, Kingston, Ontario, Canada.
J Affect Disord. 2021 Sep 1;292:416-423. doi: 10.1016/j.jad.2021.05.119. Epub 2021 Jun 15.
Globally, depression impacts nearly 300 million people, and roughly half do not achieve remission with standard first-line therapies. For such individuals, augmentation strategies are often helpful at reducing the severity of depression. While there are many potential adjunctive medication choices, psychostimulants are among the more controversial options.
The present review sought to clarify the comparative efficacy and safety of different stimulant-like medications to treat depression.
We conducted a systematic review and network meta-analysis of randomized, controlled trials (RCTs) using psychostimulant medications to treat adults with depression. Outcomes were pooled using rate ratios (RRs) for dichotomous outcomes (e.g., response, adverse events) and standardized mean differences (SMDs) for continuous outcomes (e.g., change in depression scores).
We identified 37 eligible studies (ranging from 1958 to 2016). We assessed nine psychostimulants: methylphenidate (n=14), dextroamphetamine (n=9), modafinil (n=6), lisdexamphetamine (n=3), methylamphetamine (n=3), pemoline (n=2), atomoxetine (n=1), desipramine (n=1), and imipramine (n=1). Overall, psychostimulants demonstrated efficacy for depression, reduced fatigue and sleepiness, and appeared well-tolerated. However, there was inconsistent evidence across particular psychostimulants. For example, the only psychostimulant which demonstrated efficacy for depression-in terms of both symptom severity and response rates-was methylphenidate.
While our review suggests that some psychostimulants-particularly methylphenidate-appear well-tolerated and demonstrate some efficacy for depression, as well as fatigue and sleepiness, the strength of evidence in our estimates was low to very low for most agents given the small sample sizes, few RCTs, and imprecision in most estimates. A lack of consistent evidence precludes a definitive hierarchy of treatments and points to a need for additional, high-quality RCTs.
在全球范围内，抑郁症影响着近 3 亿人，大约有一半的人无法通过标准的一线治疗缓解。对于这些人来说，通常采用增效策略来减轻抑郁的严重程度。虽然有许多潜在的辅助药物选择，但兴奋剂是更具争议性的选择之一。
本综述旨在阐明不同类兴奋剂药物治疗抑郁症的相对疗效和安全性。
我们对使用兴奋剂药物治疗抑郁症的成人进行了系统评价和网络荟萃分析，包括随机对照试验（RCT）。使用率比（RR）评估二分类结局（如反应、不良反应），标准化均数差（SMD）评估连续结局（如抑郁评分变化）来汇总结果。
我们确定了 37 项符合条件的研究（范围从 1958 年至 2016 年）。我们评估了 9 种兴奋剂：哌醋甲酯（n=14）、右旋苯丙胺（n=9）、莫达非尼（n=6）、右苯丙胺（n=3）、苯丙胺（n=3）、匹莫林（n=2）、托莫西汀（n=1）、去甲替林（n=1）和丙咪嗪（n=1）。总体而言，兴奋剂治疗抑郁症有效，可减轻疲劳和嗜睡，且耐受性良好。然而，不同的兴奋剂疗效证据并不一致。例如，在症状严重程度和反应率方面，唯一对抑郁症有效的兴奋剂是哌醋甲酯。
虽然我们的综述表明，一些兴奋剂——特别是哌醋甲酯——似乎耐受性良好，对抑郁症以及疲劳和嗜睡有一定疗效，但由于样本量小、RCT 少以及大多数估计值的不精确性，我们的估计值的证据强度为低到极低。缺乏一致的证据排除了明确的治疗等级，表明需要更多高质量的 RCT。
