Zhang Lanlan, Bao Daocheng, Wang Chengzhong
The Affiliated Maternity & Child Health Hospital of Yangzhou University, Yancheng, China.
Psychiatry Res. 2025 Jun;348:116490. doi: 10.1016/j.psychres.2025.116490. Epub 2025 Apr 11.
To evaluate the efficacy and tolerability of oral esmethadone for major depressive disorder (MDD).
We performed a computerized search of MEDLINE, EMBASE, Cochrane Library, Web of Science, Google Scholar, and ClinicalTrials.gov to identify eligible randomized, placebo-controlled trials (RCTs) until June 30, 2024. We calculated standardized mean differences (SMD) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes. Quality assessment of included RCTs was performed using the Cochrane Collaboration tool. The efficacy of esmethadone was evaluated utilizing changes from baseline in the Montgomery-Åsberg Depression Scale (MADRS) score, and tolerability was assessed in terms of serious adverse event (SAE), dropout, and the most common side effects.
A total of 3 RCTs with 521 patients were included in the current study. The changes from baseline in MADRS for SMD was -0.28 (95 % CI -0.46 to -0.10; P = 0.003), pooled RRs for response and remission were 1.38 (95 % CI 1.09-1.74; P = 0.007) and 1.82 (95 % CI 1.25-2.64, P = 0.002), respectively. Significantly more patients receiving placebo experienced discontinuation than those receiving esmethadone (RR 0.55, 95 % CI 0.32-0.96; P = 0.035). Headache, dizziness, constipation, nausea, upper respiratory tract infection, and diarrhea were the most common adverse events associated with esmethadone (RR=0.28-2.17).
Esmethadone is a rapid-onset antidepressant, showed sustained efficacy of the reduction in depression syndrome during the 14-day treatment period, with mild to moderate side effects. However, no significant difference was observed at day 28. The long-term efficacy and safety of esmethadone are still needed to evaluate in future trials.
评估口服艾司美沙酮治疗重度抑郁症（MDD）的疗效和耐受性。
我们对MEDLINE、EMBASE、Cochrane图书馆、科学网、谷歌学术和ClinicalTrials.gov进行了计算机检索，以识别截至2024年6月30日符合条件的随机、安慰剂对照试验（RCT）。我们计算了连续结局的标准化均数差（SMD）和二分结局的风险比（RR）。使用Cochrane协作工具对纳入的RCT进行质量评估。利用蒙哥马利-Åsberg抑郁量表（MADRS）评分相对于基线的变化评估艾司美沙酮的疗效，并根据严重不良事件（SAE）、退出率和最常见的副作用评估耐受性。
本研究共纳入3项RCT，涉及521例患者。SMD的MADRS相对于基线的变化为-0.28（95%CI -0.46至-0.10；P = 0.003），反应和缓解的合并RR分别为1.38（95%CI 1.09 - 1.74；P = 0.007）和1.82（95%CI 1.25 - 2.64，P = 0.002）。接受安慰剂的患者停药的比例显著高于接受艾司美沙酮的患者（RR 0.55，95%CI 0.32 - 0.96；P = 0.035）。头痛、头晕、便秘、恶心、上呼吸道感染和腹泻是与艾司美沙酮相关的最常见不良事件（RR = 0.28 - 2.17）。
艾司美沙酮是一种起效迅速的抗抑郁药，在14天的治疗期内显示出持续减轻抑郁综合征的疗效，副作用为轻至中度。然而，在第28天时未观察到显著差异。艾司美沙酮的长期疗效和安全性仍需在未来的试验中进行评估。
