title: Folates and S-adenosylmethionine for major depressive disorder.
abstract: 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.
authors: 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
authors: George I
authors: GI
authors: Papakostas
authors: Clair F
authors: CF
authors: Cassiello
authors: Nadia
authors: N
authors: Iovieno
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine; D006801:Humans; D019875:One-Carbon Group Transferases / Q000502:physiology; D011624:Pteroylpolyglutamic Acids / Q000009:adverse effects / Q000502:physiology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012436:S-Adenosylmethionine / Q000009:adverse effects / Q000502:physiology / Q000627:therapeutic use*; D013763:Tetrahydrofolates / Q000009:adverse effects / Q000502:physiology / Q000627:therapeutic use
chemical_list: D000928:Antidepressive Agents; D011624:Pteroylpolyglutamic Acids; D013763:Tetrahydrofolates; D012436:S-Adenosylmethionine; D019875:One-Carbon Group Transferases; C005984:5-methyltetrahydrofolate