Folates and S-adenosylmethionine for major depressive disorder.

George I Papakostas, Clair F Cassiello, Nadia Iovieno

Harvard Medical School and Director of Center for Treatment-Resistant Depression, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. gpapakostas@partners.org

Canadian journal of psychiatry. Revue canadienne de psychiatrie 2012 Jul

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Interest in nonpharmaceutical supplements for treating major depressive disorder (MDD) has increased signiﬁcantly, both among patients and among clinicians during the past decades. Despite the large array of antidepressants (ADs) available, many patients continue to experience relatively modest response and remission rates, in addition to a burden of side effects that can hinder treatment compliance and acceptability. In this article, we review the literature on folates and S-adenosylmethionine (SAMe), 2 natural compounds linked in the 1-carbon cycle metabolic pathway, for which substantial evidence supports their involvement in mood disorders. Background information, efﬁcacy data, proposed mechanisms of action, and side effects are reviewed. Based on existing data, supplementation with SAMe, as well as with various formulations of folates, appears to be efficacious and well tolerated in reducing depressive symptoms. Compared with other forms of folates, 5-methyltetrahydrofolate (L-methylfolate or 5-MTHF) may represent a preferable treatment option for MDD given its greater bioavailability in patients with a genetic polymorphism, and the lower risk of specific side effects associated with folic acid. Although further randomized controlled trials in this area appear warranted, SAMe and L-methylfolate may represent a useful addition to the AD armamentarium.

Citation

George I Papakostas, Clair F Cassiello, Nadia Iovieno. Folates and S-adenosylmethionine for major depressive disorder. Canadian journal of psychiatry. Revue canadienne de psychiatrie. 2012 Jul;57(7):406-13