S-Adenosylmethionine (SAMe) in major depressive disorder (MDD): a clinician-oriented systematic review

Cuomo A, Beccarini Crescenzi B, Bolognesi S, Goracci A, Koukouna D, Rossi R · Annals of General Psychiatry

Counts the comparisons rather than pooling them, which is the more honest summary of a literature this size. Of five comparisons against placebo, SAMe was significantly better in three. Of four comparisons against imipramine or escitalopram, none showed a significant difference in either direction. Of two adjunctive comparisons, one found SAMe accelerated the response to imipramine between days 4 and 12 with the scores no longer differing at day 14, and the other found SAMe added to a serotonin reuptake inhibitor better than the inhibitor alone. Side effects across the trials were mild, transient or not clinically relevant. The reviewers call the findings encouraging and say larger trials are needed before a definitive conclusion.

Population

Eight double-blind randomised controlled trials from 1984 to 2018 in major depressive disorder, 11 comparisons, 1,011 subjects, of whom 512 received SAMe

Intervention

SAMe at 200 to 3,200 mg a day, oral in most trials and intramuscular in three, for a mean of 7.3 weeks

Comparator

Placebo, or imipramine or escitalopram, or placebo added to an existing antidepressant

Limitations

A narrative systematic review with no meta-analysis and no formal risk-of-bias grading, so the count of positive comparisons carries no weighting by trial size or quality; the individual trials run from 9 to 143 participants per arm. Doses span sixteen-fold and three trials used an intramuscular route no supplement reproduces. Depression is not a joint endpoint and this record cannot lift a cartilage tier.