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Adjunctive S-adenosylmethionine (SAMe) in treating non-remittent major depressive disorder: an 8-week double-blind, randomized, controlled trial

journal contribution
posted on 2018-10-01, 00:00 authored by Jerome Sarris, Gerard J Byrne, Chad Bousman, Con Stough, Jenifer Murphy, Patricia MacDonald, Laura Adams, Sonia Nazareth, Georgina Oliver, Lachlan Cribb, Karen Savage, Ranjit Menon, Suneel Chamoli, Michael BerkMichael Berk, Chee Ng, David Mischoulon
There has been increasing interest in nutraceutical augmentation strategies to boost the efficacy of antidepressants. This study assessed whether S-adenosylmethionine (SAMe), a methyl donor that occurs naturally in the body, may be of such benefit. We conducted an 8-week, double-blind RCT in which 107 treatment non-remittent outpatients with DSM-5 diagnosed Major Depressive Disorder (MDD) were randomized to either SAMe or placebo adjunctively to antidepressants. One-carbon cycle nutrients, pertinent single nucleotide polymorphisms (SNPs), and BDNF were also analysed as potential moderators of response. A linear mixed-effects model revealed a significant overall reduction in Montgomery-Asberg Depression Rating Scale (MADRS) score across time, however there was no significant between-group difference observed (p = 0.51). Response rates at Week 8 were 54.3% in the SAMe group and 50.0% in the placebo group, with remission rates 43.5% for SAMe and 38.3% for placebo (all results NS). No effect of SAMe was found on any secondary outcome. Differential response to SAMe was not modified by a range of key genotypes (e.g. COMT), nor reflected in a change of homocysteine, red cell folate, or BDNF. Use of SAMe elicited no significant adverse effects beyond placebo, however it was implicated in one case of serotonin syndrome-like symptoms. This study concludes that 800 mg/day of SAMe is not an effective adjunctive treatment in MDD, and no obvious biomarker reflected any differential response to treatment. Due to such a distinctly high placebo-response (despite rigorous screening), future studies should employ a placebo run-in period and other strategies to minimize placebo response.



European neuropsychopharmacol






1126 - 1136




Amsterdam, The Netherlands





Publication classification

C1 Refereed article in a scholarly journal

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2018, Elsevier