Adjunctive S-adenosylmethionine (SAMe) in treating non-remittent major depressive disorder: An 8-week double-blind, randomized, controlled trial
Version 2 2024-06-06, 08:37Version 2 2024-06-06, 08:37
Version 1 2018-09-10, 14:25Version 1 2018-09-10, 14:25
journal contribution
posted on 2024-06-06, 08:37authored byJ Sarris, GJ Byrne, C Bousman, C Stough, J Murphy, P MacDonald, L Adams, S Nazareth, G Oliver, L Cribb, K Savage, R Menon, S Chamoli, Michael BerkMichael Berk, C Ng, D 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.