Do SAMe Supplements Work in Depression?

The burgeoning body of evidence supporting complementary and alternative medicine (CAM) for depression should encourage providers to employ it in patients with mild-to-moderate disease and those resistant to pharmacologic and psychologic therapies.

About 10% to 30% of patients with depression use CAM (sometimes without provider knowledge) because of their preference for self-directed therapy, favorable adverse effect profiles, lower cost, or perceived superior efficacy.

Depressed patients in the United States and Canada have been known to use OTC oral supplements of S-adenosylmethionine (SAMe), an endogenous methyl donor involved in monoaminergic neurotransmission. Typical dosing is 800 to 1600 mg/day by mouth in divided doses for 4 to 12 weeks. Patients given SAMe intramuscularly or intravenously at lower doses achieved superior efficacy in previous research.

The August 2016 issue of The Canadian Journal of Psychiatry included updated Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines, which were based on a literature search of systematic reviews and meta-analyses on CAM published between 2009 and 2015.

According to the guidelines, first- and second-line therapy for mild-to-moderate depression includes exercise, light therapy, St. John’s wort, omega-3 fatty acids, yoga, and SAMe. Patients can add exercise or SAMe to moderate-to-severe depression therapy, while providers can consider other therapies with little or weak efficacy evidence for third-line use.

SAMe is an effective adjunctive agent in mild-to-moderate major depressive disorder. The results of 2 systematic reviews suggested that SAMe is noninferior to placebo for mild-to-severe depression and to antidepressants for mild-to-moderate depression. SAMe’s most common side effects are tolerable and include gastrointestinal upset, insomnia, sweating, headache, irritability, restlessness, tachycardia, and fatigue.

SAMe is an effective adjunctive agent in mild-to-moderate major depressive disorder. The results of 2 systematic reviews suggested that SAMe is noninferior to placebo for mild-to-severe depression and to antidepressants for mild-to-moderate depression. SAMe’s most common side effects are tolerable and include gastrointestinal upset, insomnia, sweating, headache, irritability, restlessness, tachycardia, and fatigue.

The CANMAT guideline authors made few changes in the 2016 update, but the evidence for CAM has strengthened and deepened. Patients can use both supplements and lifestyle modifications as monotherapy in mild-to-moderate depression, or adjunctively with pharmacologic and psychologic therapy in mild-to-severe depression.