SAM-e Offers Hope When Antidepressants Do Not Work
York NY, 5 May 2004
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.
Findings Presented Today at the American Psychiatric Association
Annual Meeting in New York City
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.
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.
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.
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
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
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.
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,
efficacy measures included the Montgomery Asberg Depression Rating
Scale (MADRAS), the Clinical Global ImpressionsSeverity (CGI-S),
Improvement (CGI-I) scales and the 90 item Kellner Symptom Questionnaire
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
patient experienced a serious adverse event. Moderate side effects
reported in the trial include constipation, GI upset and headaches.
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.
(SAM-e) is a naturally occurring methyl donor in mammals and has
been available in the United States in recent years as a dietary
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.
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.)
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.
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
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
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.
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.
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
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).
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.
Source: Supported by Pharmavite.