Efficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients: A systematic review and meta- analysis

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 (N = 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, I2 = 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, I2 = 76%); and iii) SAMe did not exhibit a significant difference from ADs alone (SMD = 0.06, 95%CI = −0.06 to 0.18, I2 = 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.