News Release

Small study shows SAMe may improve treatment of depression

Adding supplement to antidepressant medication can help patients with continuing symptoms

Peer-Reviewed Publication

Massachusetts General Hospital

Massachusetts General Hospital (MGH) researchers have found that adding the nutritional supplement SAMe to a standard antidepressant may be helpful to patients who have not responded to single-drug treatment for clinical depression. The pilot study, appearing in the December Journal of Clinical Psychopharmacology, found that treatment with both SAMe and an antidepressant improved symptoms in half the study participants and produced complete relief of symptoms in 43 percent of participants.

"One of the most common problems in treating depression is the number of people who are left with symptoms after initial treatment with a first-line antidepressant," says Jonathan Alpert, MD, associate director of the MGH Depression and Clinical Research Program, who led the study. "Some previous trials have suggested that SAMe might have effects comparable to some antidepressants, but there has not been sufficient research on oral SAMe preparations or comparisons with available antidepressants."

A substance that is found in every human cell, SAMe (S-Adenosy-L-Methionine) is a commonly used dietary supplement. Although some reports had suggested it might be useful in treating depression, few rigorous research trials have been carried out. The current study was designed to investigate whether adding SAMe to antidepressant treatment could improve the results for patients for whom a single medication had not relieved symptoms.

The study enrolled 30 participants who had continued to have significant depression after more than a month of treatment with drugs like Prozac, Paxil or Effexor. During the six-week study, participants received SAMe along with their antidepressant, starting at 400 mg of SAMe two times a day and increasing to 800 mg twice a day after two weeks. Patients were free to stay at or return to the 400 mg dose level if they chose to, in consultation with their physician.

At the end of the study period, analysis with several standard tools for measuring symptoms of depression showed that 50 percent of participants had significant improvement in their symptoms and 43 percent had complete remission of their depression. Although two participants dropped out because of treatment side effects, there were no reports of serious adverse events.

"This is the first study to look at the safety and efficacy of combining SAMe with antidepressant treatment after antidepressants had proven insufficient on their own," says Alpert. "Patients and physicians have been using these combinations without good supporting data, and these results are an initial step toward compiling the necessary scientific evidence."

The MGH team notes that the current study has many limitations – including its small size, the lack of a control group and the fact that participants knew they were taking an active dose of SAMe. The researchers have just begun a National Institutes of Health (NIH)-sponsored, double-blinded, placebo controlled trial of SAMe in combination with antidepressant treatment. A second NIH-funded study will compare SAMe with standard antidepressants and with placebo as a single-drug therapy. More information on these new studies is available toll-free at 877 55-BLUES (877 552-5837).

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The current study was sponsored by Pharmavite LLC, which manufactures the Nature Made line of vitamins and nutritional supplements. The study's co-authors are senior author Maurizio Fava, MD, George Papakostas, MD, David Mischoulon, MD, PhD, John Worthington, MD, Timothy Petersen, PhD, Yasmin Mahal, Alana Burns, and Andrew Nierenberg, MD, all of the MGH Depression and Clinical Research Program; and Teodoro Bottiglieri, PhD, of Baylor University.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $400 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.


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