This systematic review and meta-analysis aimed to assess the efficacy and acceptability of S-adenosyl-L-methionine (SAMe) in treating depression. We conducted a comprehensive search of PubMed, Embase, Cochrane Library, and ClinialTrials.gov from inception to July 3, 2023, identifying randomized controlled trials comparing SAMe with placebo or antidepressants (ADs). We synthesized data on reduced depressive symptoms (efficacy) and overall dropout rates (acceptability) using a random-effects model for pairwise frequentist meta-analysis. Our analysis included 23 trials ( = 2183) classified into three categories: 11 trials comparing SAMe and placebo, 5 trials comparing SAMe plus ADs and placebo plus ADs, and 7 trials comparing SAMe and ADs. Differences between experimental and control interventions in reducing depressive symptoms were observed: i) SAMe demonstrated significantly superior efficacy compared to placebo (SMD = −0.58, 95% CI = −0.93 to −0.23, = 68%); ii) in conjunction with ADs, SAMe did not show a significant difference from placebo (SMD = −0.22, 95%CI = −0.63 to 0.19, = 76%); and iii) SAMe did not exhibit a significant difference from ADs alone (SMD = 0.06, 95%CI = −0.06 to 0.18, = 49%). No significant differences in dropout rates were observed across the three comparison categories. Moderate-certainty evidence suggests that SAMe monotherapy may offer a moderate therapeutic benefit in alleviating depressive symptoms. Considering its favorable acceptability profile, SAMe monotherapy should be considered as a treatment option for patients with depression. However, uncertainties regarding its efficacy as an adjunct to AD and its comparative efficacy with ADs remain unresolved.

中文翻译：

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S-腺苷-L-蛋氨酸（SAMe）对抑郁症患者的疗效和可接受性：系统评价和荟萃分析

这项系统评价和荟萃分析旨在评估 S-腺苷-L-甲硫氨酸 (SAMe) 治疗抑郁症的功效和可接受性。我们对 PubMed、Embase、Cochrane Library 和 ClinialTrials.gov 从成立到 2023 年 7 月 3 日期间进行了全面检索，确定了将 SAMe 与安慰剂或抗抑郁药 (AD) 进行比较的随机对照试验。我们使用随机效应模型进行成对频率主义荟萃分析，综合了有关减少抑郁症状（功效）和总体辍学率（可接受性）的数据。我们的分析包括 23 项试验 (= 2183)，分为三类：11 项比较 SAMe 和安慰剂的试验，5 项比较 SAMe 加 AD 和安慰剂加 AD 的试验，以及 7 项比较 SAMe 和 AD 的试验。观察到实验干预措施和对照干预措施在减少抑郁症状方面的差异： i) SAMe 与安慰剂相比表现出显着优越的功效（SMD = -0.58，95% CI = -0.93 至 -0.23，= 68%）；ii) 与 AD 结合使用时，SAMe 与安慰剂相比没有显示出显着差异（SMD = -0.22，95%CI = -0.63 至 0.19，= 76%）；iii) SAMe 与单独的 AD 没有表现出显着差异（SMD = 0.06，95%CI = -0.06 至 0.18，= 49%）。在三个比较类别中没有观察到辍学率存在显着差异。中等质量的证据表明，SAMe 单一疗法可能在缓解抑郁症状方面提供中等的治疗益处。考虑到其良好的可接受性，SAMe 单一疗法应被视为抑郁症患者的一种治疗选择。然而，其作为 AD 辅助药物的功效及其与 AD 的比较功效的不确定性仍未解决。