• George I Papakostas, David Mischoulon, Irene Shyu, Jonathan E Alpert, and Maurizio Fava.
• Center for Treatment-Resistant Depression, Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, 15 Parkman St., Boston, MA 02114, USA. gpapakostas@partners.org
• Am J Psychiatry. 2010 Aug 1; 167 (8): 942-8.

ObjectiveDespite the progressive increase in the number of antidepressants, many patients with major depressive disorder continue to be symptomatic. Clearly, there is an urgent need to develop better tolerated and more effective treatments for this disorder. The use of S-adenosyl methionine (SAMe), a naturally occurring molecule that serves as a methyl donor in human cellular metabolism, as adjunctive treatment for antidepressant nonresponders with major depressive disorder represents one such effort toward novel pharmacotherapy development.MethodParticipants were 73 serotonin reuptake inhibitor (SRI) nonresponders with major depressive disorder enrolled in a 6-week, double-blind, randomized trial of adjunctive oral SAMe (target dose: 800 mg/twice daily). Patients continued to receive their SRI treatment at a stable dose throughout the 6-week trial. The primary outcome measure for the study was the response rates according to the 17-item Hamilton Depression Rating Scale (HAM-D).ResultsThe HAM-D response and remission rates were higher for patients treated with adjunctive SAMe (36.1% and 25.8%, respectively) than adjunctive placebo (17.6% versus 11.7%, respectively). The number needed to treat for response and remission was approximately one in six and one in seven, respectively. There was no statistically significant difference in the proportion of SAMe- versus placebo-treated patients who discontinued the trial for any reason (20.6% versus 29.5%, respectively), due to adverse events (5.1% versus 8.8%, respectively), or due to inefficacy (5.1% versus 11.7%, respectively).ConclusionsThese preliminary results suggest that SAMe can be an effective, well-tolerated, and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder and warrant replication.

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