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S-Adenosyl-L-Methionine (SAMe) as an Adjunct for Resistant Major Depressive Disorder: An Open Trial Following Partial or Nonresponse to Selective Serotonin Reuptake Inhibitors or Venlafaxine

Alpert, Jonathan E. MD, PhD*; Papakostas, George MD*; Mischoulon, David MD, PhD*; Worthington, John J. III MD*; Petersen, Timothy PhD*; Mahal, Yasmin BA*; Burns, Alana BA*; Bottiglieri, Teodoro PhD; Nierenberg, Andrew A MD*; Fava, Maurizio MD*

Journal of Clinical Psychopharmacology: December 2004 - Volume 24 - Issue 6 - p 661-664
doi: 10.1097/
Brief Reports

Background: The purpose of this open trial was to evaluate the safety, tolerability, and efficacy of oral S-adenosyl-l-methionine as an antidepressant adjunct among partial and nonresponders to serotonin reuptake inhibitors or venlafaxine.

Method: Thirty antidepressant-treated adult outpatients with persisting major depressive disorder received 800 to 1600 mg of S-adenosyl-l-methionine tosylate over a 6-week trial.

Results: Intent-to-treat analyses based on the Hamilton Depression Rating Scale revealed a response rate of 50% and a remission rate of 43% following augmentation with S-adenosyl-l-methionine. Gastrointestinal symptoms and headaches were the most common side effects.

Conclusion: Augmentation of selective serotonin reuptake inhibitors or venlafaxine with S-adenosyl-l-methionine warrants a placebo-controlled trial in resistant depression.

*Depression Clinical and Research Program, Massachusetts General Hospital, Department of Psychiatry, Harvard Medical School, Boston, MA and †Baylor Institute of Metabolic Disease, Dallas, TX.

Received December 11, 2003; accepted after revision June 28, 2004.

Address correspondence and reprint requests to Jonathan E. Alpert, MD, PhD, Massachusetts General Hospital, Depression Clinical and Research Program, 50 Staniford Street, 4th floor, Boston, MA 02114. E-mail:

© 2004 Lippincott Williams & Wilkins, Inc.