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Aug. 2, 2000 -- Thousands of Americans are taking an over-the-counter nutritional supplement called SAMe (S-adenosylmethionine) for its purported antidepressant effects. But a recent look at the research to date concludes that although SAMe (pronounced SAME) appears to have some effect, the effects are modest, and much of the evidence supporting its use is weak.
In addition, many SAMe preparations recently were found by a consumer-testing lab to be inaccurately labeled, so consumers may not be taking the proper doses.
"Based on these published reports, it is premature to consider SAMe to be a reliable and clinically significant antidepressant," writes researcher John C. Echols, MD, of the Massachusetts General Hospital in Boston, in his review article published in the Harvard Review of Psychiatry.
Proponents of using SAMe for depression, such as Richard Brown, MD, of Columbia University, disagree. He says the researchers need to take a better look at the existing studies, "and they also need experience with SAMe. They're giving the common view of people who do not know much about SAMe," says Brown, who commented on the study for WebMD.
SAMe is a naturally occurring substance in the body. It is involved in the formation of a variety of important bodily substances, including chemicals that are believed to be associated with depression.
Some researchers have hypothesized that low levels of SAMe in the body contribute to depression. Studies have shown that some people with depression have low SAMe levels, and that levels of SAMe rise as depression improves, Echols says.
Echols analyzed the results of 14 studies in which the effects of SAMe on depressed patients was compared to that of either dummy pills or to a group of older prescription antidepressants, called tricyclics, which are used infrequently nowadays.
In most of the studies, SAMe was found to be only modestly effective or not effective at all, Echols says. Unfortunately, most of the studies were flawed, so their results are difficult to interpret.
Brown, author of the book Stop Depression Now, began treating patients with SAMe about seven years ago. He offers it as one option for antidepressant therapy, especially for patients who are resistant to, or intolerant of, standard antidepressant therapy. He says that Echols missed many recent studies of SAMe in his review. Still, he says, all the studies cited by Echols are consistent in their findings that SAMe works better than dummy pills and is as effective as the tricyclics.
Ron Pies, MD, clinical professor of psychiatry at Tufts University School of Medicine in Boston, takes a more neutral stance. More study is needed, he says. "I don't think we know a great deal about SAMe in relation to other available options," he says. "I do think the data look promising. I don't believe this is just a fad or a hoax. I think SAMe ... probably does have antidepressant effects."
The effectiveness of SAMe, compared to that of traditional and newer antidepressants, is not yet clear, Echols says. More studies comparing SAMe to the newer class of prescription antidepressants, called SSRIs, are especially needed, says Pies, who is a medical adviser to WebMD. More information also is needed on the use of SAMe in combination with other antidepressants, he says. "I believe future research will show that adding SAMe to a number of antidepressants helps improve the response to the antidepressant," Brown tells WebMD.
One of the known risks of SAMe is its capacity to cause mania. Symptoms of mania include strong feelings of happiness or irritability, inflated self-esteem, decreased need for sleep, increased talkativeness, poor concentration, and racing thoughts.
SAMe should not be used by itself in manic-depressive patients, who are especially susceptible to becoming manic, Pies tells WebMD. "The good news is that the ability of SAMe to produce mania indicates it has antidepressant properties," he says. "The bad news is that there are a lot of people who are taking SAMe who are either unsupervised or may not know they are at risk for developing mania. ... I think that's extremely risky."
Another thorny issue is the potency and purity of SAMe preparations sold in the U.S. Tod Cooperman, MD, is the president of ConsumerLab.com, an independent rating service that recently analyzed the content of 13 brands of SAMe available in the U.S. "About 40% of products that we tested didn't contain what a consumer would expect from their labels," Cooperman tells WebMD.
For instance, some products whose labels said they contained 200 mg of SAMe actually had only 100 mg of SAMe, along with100 mg of an inactive stabilizer. Cooperman says he can't tell whether these inaccuracies were unintentional, or resulted from manufacturers trying to skimp on an expensive ingredient.
Pies thinks this is a big problem for consumers. "Many consumers just walk into the supermarket and grab a bottle of SAMe -- and they don't really know what they're getting," he says.
Despite these concerns, Brown believes many people with depression can benefit from SAMe, including the elderly, children, and people with AIDS: "I help people the best way I know, and you have to have a lot of ways to do it. ... SAMe is a choice people need to know about." He praises his patients for taking the initiative of finding out about SAMe, often through the Internet, and for helping themselves when other treatments have failed.
But this can be a dangerous approach to treating depression, Pies says: "Depression is not a 'do-it-yourselfer'. Too many people are being directed toward these nontraditional therapies on their own, by books, or the Internet. They're not getting adequately assessed and not getting adequate treatment -- and that's very distressing."
For more information from WebMD, see our Diseases & Conditions page on Depression.