Zhou Shuzhe, Li Pei, Lyu Xiaozhen, Lai Xuefeng, Liu Zuoxiang, Zhou Junwen, Liu Fengqi, Tao Yiming, Zhang Meng, Yu Xin, Tian Jingwei, Sun Feng
Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing 100191, China.
NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China.
Chin Med J (Engl). 2025 Jun 20;138(12):1433-1438. doi: 10.1097/CM9.0000000000003138. Epub 2024 Jun 20.
The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships in the treatments of major depressive disorders (MDD).
We searched multiple databases, including the Embase, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science, for the studies that were conducted between January 8, 2016, and April 30, 2023. The studies are double-blinded, randomized controlled trials (RCTs) involving the adults (≥18 years) with MDD. The primary outcomes were efficacy of antidepressant and the dose-response relationships. A frequentist network meta-analysis was conducted, treating participants with various dosages of the same antidepressant as a single therapy. We also implemented the model-based meta-analysis (MBMA) using a Bayesian method to explore the dose-response relationships.
The network meta-analysis comprised 135,180 participants from 602 studies. All the antidepressants were more effective than the placebo; toludesvenlafaxine had the highest odds ratio (OR) of 4.52 (95% confidence interval [CI]: 2.65-7.72), and reboxetine had the lowest OR of 1.34 (95%CI: 1.14-1.57). Moreover, amitriptyline, clomipramine, and reboxetine showed a linear increase in effect size from low to high doses. The effect size of toludesvenlafaxine increased significantly up to 80 mg/day and subsequently maintained the maximal dose up to 160 mg/day while the predictive curves of nefazodone were fairly flat in different dosages.
Although most antidepressants were more efficacious than placebo in treating MDD, no consistent dose-response relationship between any antidepressants was observed. For most antidepressants, the maximum efficacy was achieved at lower or middle prescribed doses, rather than at the upper limit.
No. CRD42023427480; https://www.crd.york.ac.uk/prospero/display_record.php?
最佳抗抑郁药剂量仍存在争议。本研究旨在分析抗抑郁药的疗效，并描述其在治疗重度抑郁症（MDD）中的剂量反应关系。
我们检索了多个数据库，包括Embase、Cochrane对照试验中央注册库、PubMed和Web of Science，以查找2016年1月8日至2023年4月30日期间进行的研究。这些研究为双盲随机对照试验（RCT），涉及患有MDD的成年人（≥18岁）。主要结局是抗抑郁药的疗效和剂量反应关系。进行了频率学派网络荟萃分析，将使用不同剂量的同一种抗抑郁药治疗的参与者视为单一疗法。我们还使用贝叶斯方法实施了基于模型的荟萃分析（MBMA），以探索剂量反应关系。
网络荟萃分析纳入了来自602项研究的135,180名参与者。所有抗抑郁药均比安慰剂更有效；托度司韦拉法辛的优势比（OR）最高，为4.52（95%置信区间[CI]：2.65 - 7.72），瑞波西汀的OR最低，为1.34（95%CI：1.14 - 1.57）。此外，阿米替林、氯米帕明和瑞波西汀的效应大小从低剂量到高剂量呈线性增加。托度司韦拉法辛的效应大小在每日80毫克时显著增加，随后在高达160毫克/天的剂量下维持最大效应，而奈法唑酮在不同剂量下的预测曲线相当平坦。
尽管大多数抗抑郁药在治疗MDD方面比安慰剂更有效，但未观察到任何抗抑郁药之间一致的剂量反应关系。对于大多数抗抑郁药，在较低或中等处方剂量下达到最大疗效，而非上限剂量。
编号CRD42023427480；https://www.crd.york.ac.uk/prospero/display_record.php?
