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SAM-e Offers Hope When Antidepressants Do Not Work

New York NY, 5 May 2004
Source: CO2

Research at Massachusetts General Hospital indicates that antidepressants used in combination with dietary supplement SAM-e were significantly more effective in relieving depression than medication alone.

Study Findings Presented Today at the American Psychiatric Association Annual Meeting in New York City

More than 18 million Americans a year are diagnosed with major depression. Five out of 10 of those people will not respond or will only partially respond to standard antidepressant treatment, or they will discontinue use because of side effects.

The Boston-based Massachusetts General Hospital (MGH) study findings presented today at the American Psychiatric Association Annual meeting indicate that the addition of dietary supplement S-adenosylmethionine, better known as SAM-e (pronounced "sammy"), to a patient's current selective serotonin SSRI (most widely used antidepressants such as Zoloft, Paxil, Prozac) regimen, improves patient response.

"The SAM-e/antidepressant combination was comparable to that of two antidepressants, with faster onset of action and fewer side effects such as weight gain and sexual dysfunction," says Jonathan Alpert, MD, PhD, associate director of the depression clinical and research program at Massachusetts General Hospital and lead investigator of the trial.

"It is common practice for physicians to add a second agent with established or putative antidepressant properties when one alone does not help a patient," adds Alpert. "Recently, interest has increased in adding dietary supplements and other complementary therapies to current treatment options."

"SAM-e is known for having few side effects and being well tolerated," says Maurizio Fava, MD, associate chief of psychiatry for clinical research and the director of the Mass General Hospital Depression Clinical and Research Program. "Based on the trial results, we feel it may be a more acceptable solution for patients who require combination therapy."

Study details

The open trial was designed to evaluate the safety, tolerability and efficacy of oral SAM-e tosylate as an antidepressant adjunct. The trial included thirty patients with current Major Depressive Disorder (MDD) despite an adequate dose of a single Selective Serotonin Reuptake Inhibitor (SSRI), the most common class of antidepressants or venlafaxine (Effexor XR). The patients were given 800 to 1,600 mg of SAM-e over six weeks. The mean patient age was 48.4 +/- 13.0 years.

The primary outcome test was the number of responders and remitters. A responder was defined as someone with a 50 percent reduction in HAM-D-17 score from baseline to endpoint. A remitter was defined as someone who had a final HAM-D-17 score greater than or equal to seven. (Overall, 93% of patients improved. See results, below).

Secondary efficacy measures included the Montgomery Asberg Depression Rating Scale (MADRAS), the Clinical Global Impressions—Severity (CGI-S), Improvement (CGI-I) scales and the 90 item Kellner Symptom Questionnaire (SQ).

When used in combination with prescription antidepressants, SAM-e was associated with a 50 percent intent-to-treat response rate, acceptable tolerability, no weight gain, and statistically significant reductions in reported sexual dysfunction, anxiety symptoms and serum homocysteine levels.

No patient experienced a serious adverse event. Moderate side effects reported in the trial include constipation, GI upset and headaches.

Pharmavite LLC funded the trial and provided the active ingredient. The promising results of this preliminary study provide the basis for a larger, controlled follow-up study that is being funded by the National Institutes of Health.

About SAM-e

S-adenosylmethionine (SAM-e) is a naturally occurring methyl donor in mammals and has been available in the United States in recent years as a dietary supplement.

SAM-e is involved in more than 35 biochemical processes in the human body. SAM-e's broad metabolic role in all tissues, including the brain, suggests that its antidepressant mechanisms may include increasing the availability of neurotransmitters, such as serotonin and dopamine, as well as increasing the number of neurotransmitter receptors.

In December 2002, the Agency for Healthcare Research and Quality (AHRQ) reviewed 39 placebo or active-controlled clinical trials, involving a total of 2,485 patients, on the role SAM-e has in treating depression. AHRQ concluded that SAM-e is more effective than placebo, and is as effective as standard prescription medication for treating patients with major depression. (See full summary of the research: www.ahrq.gov/clinic/epcsums/samesum.htm.)

Literature References

[1] Mischoulon D, Fava. "Role of S-adenosyl-L-methionine in the treatment of depression: A review of the evidence." Am J Clin Nutr. 2002; 76(5): 1158S-61S.

[2] Hardy M, Coulter I, Morton SC, et al. "S-Adenosyl-L-Methionine for Treament of Depression, Osteoarthritis, and Liver Disease." AHRQ Publication No. 02-E04. Rockville, MD.


Title: Oral S-Adenosyl Methionine (SAMe) for Antidepressant Augmentation: Open-label Trial

Educational Objectives: Recognize the potential role of oral SAMe when used in conjunction with selective serotonin reuptake inhibitors or venlafaxine in the treatment of major depressive disorder.

Background: To evaluate the safety, tolerability and efficiency of oral SAMe 800-1600mg/day for augmentation of conventional antidepressants among adults with Major Depressive Disorder (MDD) with partial or non-response to a standard course of serotonin reuptake inhibitors (SSRI) or venlafaxine.

Methods: 30 adult outpatients (22 female, age 48.4 +/- 13.0 years, mean baseline HAM-D-17 score 17.7 +/- 14.2) with retrospectively established treatment resistance to adequate dose/duration of an SSRI or venlafaxine received open-label adjunctive treatment with oral SAMe starting at 800mg/day for 2 weeks and increased to 1600mg/day, depending upon response and tolerability, for an additional 4 week period. Response was defined as 50% or greater decrease from baseline to endpoint in the HAM-D-17. Remission was defined as an endpoint HAM-D-17 score of less than or equal to 7.

Results: Intent-to-treat analysis indicated a significant decrease in depression severity from baseline to endpoint as measured by the HAM-D-17 (p less than 0.0001) and the BDI (p=0.0002). At endpoint, there were

  • 15 (50.0%) responders
  • 13 (43.3%) remitters

Benign safety and tolerability data included a decrease in pre- to post-treatment homocysteine levels (from 8.2 +/- 2.5 to 7.8 +/- 2.3 mol/liter, p=0.0029).

Conclusions: The combination of a stable oral form of SAMe with an SSRI or venlafaxine may offer an additional treatment strategy among outpatients with resistant MDD.

Funding Source: Supported by Pharmavite.




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