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Evidence for S-Adenosyl-L-Methionine (SAM-e) for the Treatment of Major Depressive Disorder

J Clin Psychiatry 2009;70(suppl 5):18-22
10.4088/JCP.8157su1c.04

Despite the increasingly large array of antidepressants available to treat major depressive disorder, patients continue to experience relatively modest response and remission rates. In addition, patients may experience adverse side effects from pharmacotherapy that not only hinder treatment compliance and adherence but, in some cases, may also contribute to increased disability, patient suffering, morbidity, and mortality. In order to enhance treatment efficacy and tolerability,patients and clinicians have become increasingly interested in nonpharmaceutical supplements for treating depression. One of the best-studied of these supplements is S-adenosyl-l-methionine(SAM-e), a naturally occurring molecule present in all living cells and a major methyl group donor in the human body. Controlled trials have found SAM-e to be more efficacious than placebo and equal in efficacy to the tricyclic antidepressants for treating major depressive disorder (MDD) when administered parenterally (either intravenously or intramuscularly). Less evidence supports the use of oral SAM-e,although some trials have demonstrated its efficacy as well. In addition, there is a paucity of evidence examining whether oral forms of SAM-e can be safe, well tolerated, and efficacious when used as adjunctive treatment for antidepressant nonresponders with MDD. Although preliminary data suggest SAM-e may be useful as an adjunctive therapy to antidepressants, controlled studies are needed to confirm or refute these preliminary findings.


From the Department of Psychiatry, Harvard Medical School and Massachusetts General Hospital, Boston.

This article is derived from the planning teleconference series “The Use of Complementary and Alternative Medicines to Achieve Remission in Major Depressive Disorder,” which was held in May 2009 and supported by an educational grant from Pamlab, LLC.

Lifetime financial disclosure as of July 14, 2009: Dr Papakostas has served as an advisor/consultant for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly, Evotec, Inflabloc, Jazz, Shire, Titan, Otsuka, Pfizer, Pierre Fabre, Wyeth, and Pamlab; has received grant/research support from the National Institute of Mental Health, Pamlab, Pfizer, Forest, Precision Human Biolaboratories, and Bristol-Myers Squibb; and has received honoraria from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly, Evotec, Inflabloc, Jazz, Shire, Otsuka, Pierre Fabre, Pfizer, Pamlab, Titan, Wyeth, and Lundbeck.

Corresponding author: George I. Papakostas, MD, Massachusetts General Hospital, 15 Parkman St WACC #812, Boston, MA 01224 (gpapakostas@partners.org).