SAMe Shows Promise for Depression Treatment

Supplement may help those who don't respond to meds alone

/ Author:  / Reviewed by: Joseph V. Madia, MD

(RxWiki News) Researchers at Harvard Medical School and Massachusetts General Hospital (MGH) have found that dietary supplement S-Adenosyl Methionine (SAMe) may help adults with major depressive disorders who do not respond to treatment with antidepressant medication alone. The study, funded by a grant from the National Institutes of Mental Health, marks the first randomized, placebo-controlled clinical trial conducted on patients with major depressive disorders.


A total of 73 adults took part in the six-week clinical trial and were randomly assigned to the placebo or SAMe treatment group. Those assigned to the SAMe group reported improved measures of depression and remission rates of significant clinical depression compared to those who received a placebo with standard depression treatment. No patient reported adverse reactions to SAMe.

Lead author of the study George Papakostas, M.D., associate professor of psychiatry at Harvard Medical School and director of treatment-resistant depression studies in the Department of Psychiatry at MGH, said that although the findings call for an urgent need for replication, they suggest “significant, clinically meaningful differences in outcome among patients who had SAMe added to their antidepressant medication treatment compared to those taking a placebo with their medication.”

After six weeks of treatment, 36 percent of the patients taking a combination of SAMe and antidepressant medication showed improvement, compared to half that percentage who showed improvement taking an antidepressant and placebo. Even more startling, about 26 percent of those taking SAMe with standard treatment reported complete remission of symptoms compared to 12 percent who reported the same remission with a placebo. 

Papakostas said these preliminary findings support “the efficacy, safety, and tolerability of SAMe as an additive therapy for patients with major depressive disorders who do not respond to antidepressant treatment alone.”

J. Craig Nelson, M.D., professor of psychiatry at the University California, San Francisco, wrote in an accompanying editorial of the August 2010 American Journal of Psychiatry, “SAMe offers a novel mechanism of treatment action and opens up a new area for future exploration” as the era of development for new amine reuptake inhibitors appears to fade.

Although it isn’t clear how SAMe helps curb depression, the supplement may influence the gene expression involved in depression or alter the function of different receptors and structures that transport neurotransmitters in the brain.

As most antidepressants act on neurotransmitters, SAMe might facilitate “the synthesis of the neurotransmitters that the drugs then act on,” Nelson wrote. “That’s probably the best hypothesis.”

In any case it appears SAMe acts as an effective, well-tolerated and safe adjunctive treatment for those with major depressive disorders who do not respond to antidepressant medication alone.

Reviewed by: 
Review Date: 
September 15, 2010
Last Updated:
February 16, 2011