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Is SAMe Worthwhile for Depression?

What can you tell me about SAMe? Is it really effective for treatment of depression? 

Answer (Published 11/8/2011)

SAMe (S-adenosy-L-methionine) is a naturally occurring molecule found throughout the body, with high concentrations in the adrenal glands, liver, and brain. It has been studied extensively as an antidepressant as well as for treatment of osteoarthritis pain. Although the study populations have been small, results have generally been positive, showing SAMe to be more effective than placebo. In research reported in August, 2010, in the American Journal of Psychiatry, investigators from Harvard Medical School and Massachusetts General Hospital gave either SAMe or a placebo to 73 depressed adults who had not responded to prescribed antidepressant drugs; all continued to take the drugs. After six weeks of treatment, 36 percent of the subjects taking SAMe showed improvement, compared to just 18 percent of the placebo group. Moreover, 26 percent of those in the SAMe group had complete remission of symptoms, compared to just 12 percent in the placebo group. SAMe doesn’t work for everyone, but neither do antidepressant drugs.

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We don’t know how SAMe works. It may affect levels of neurotransmitters, chemicals produced naturally in the body that facilitate communication between nerve cells in the brain and between nerve cells and the rest of the body. An advantage of SAMe over prescription antidepressants and the herbal remedy St. John’s wort is that it works quickly, often lifting mood within days rather than weeks. Antidepressants take at least four weeks to kick in; St. John’s wort as long as two months.

SAMe is also quite safe. However, because it has been reported to worsen manic symptoms, those with bipolar disorder should avoid it. The only side effect, which is uncommon, is gastrointestinal upset. If you want to try SAMe, look for products that provide the butanedisulfonate form in enteric-coated tablets. The usual dosage is 400 to 1,600 milligrams a day, taken on an empty stomach. Lower doses (under 800 milligrams) should be taken once a day, a half hour before the morning meal; higher doses should be split, taking the second a half hour before lunch. You can use SAMe in conjunction with prescribed antidepressants (and other medications). It may be especially useful for people who suffer from pain as well as depression.

For a full discussion of natural remedies for depression, including SAMe, and an integrative plan for optimum emotional well-being, watch for my new book, Spontaneous Happiness, to be published by Little, Brown & Co. on November 8, 2011.

Andrew Weil, M.D.

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