Laurie Barclay, MD (Source: MedScape)
Oct. 15, 2002 — The U.S. Agency for Healthcare Research and Quality (AHRQ), a division of the Department of Health and Human Services, has assembled the evidence available on s-Adenosyl-L-Methionine (SAMe) and has shown actual benefit for the treatment of depression, osteoarthritis, and liver disease.
“The [AHRQ] report indicates that that this is a compound worthy of further investigation,” Maurizio Fava, MD, director of the depression clinic and research program at Massachusetts General Hospital in Boston, tells Medscape. “True, these are very small studies, but they consistently suggest the efficacy of this compound in depression.”
In treating depression, SAMe is more effective than placebo and as effective as standard antidepressants, with fewer adverse effects. Compared with nonsteroidal anti-inflammatory drugs (NSAIDs), SAMe also relieves the pain of osteoarthritis, but with fewer gastrointestinal adverse effects. It also reduces cholestasis secondary to use of oral contraceptives or estrogen, pregnancy, or birth defects, for which there is currently no other effective treatment.
The AHRQ report reviewed the literature on the use of SAMe in these conditions and identified 294 meta-analyses, clinical trials, and reports, of which 99 articles referencing 102 studies met the screening criteria. Of these 102 studies, most of which enrolled small numbers of patients, 47 focused on depression, 14 focused on osteoarthritis, and 41 focused on liver disease.
In a meta-analysis of 28 studies, treatment with SAMe was associated with an improvement, compared with placebo, of approximately 6 points on the Hamilton Rating Scale for Depression score measured at three weeks (95% confidence interval [CI], 2.2 to 9.0). Compared with conventional antidepressants, treatment with SAMe was not associated with a statistically significant difference in outcomes.
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“We’ve never had a large double-blind study [of SAMe in depression] in the U.S.,” Fava says. It’s time for researchers to look at this more closely.”
Of 13 unique studies considered, 10 studies were included in a meta-analysis of the efficacy of SAMe to decrease the pain of osteoarthritis. In one large randomized clinical trial, SAMe reduced the pain of osteoarthritis by 20% (95% CI, -0.39 to – 0.02) compared with placebo, which was not significantly different from results with NSAIDs.
In a meta-analysis of eight studies of the efficacy of SAMe to relieve pruritus and decrease elevated serum bilirubin levels associated with cholestasis of pregnancy, treatment with SAMe was associated with an effect size compared with placebo of nearly a full standard deviation (-0.95; 95% CI, -1.45 to -0.45) for decrease in pruritus and of over one and one-third standard deviations (-1.32; 95% CI, -1.76 to -0.88) for decrease in serum bilirubin levels.
Two clinical trials which were not pooled favored ursodeoxycholic acid over SAMe for the treatment of pruritus. In a meta-analysis of six studies of the efficacy of SAMe to relieve pruritus and decrease elevated bilirubin levels associated with intrahepatic cholestasis, treatment with SAMe for pruritus was more than twice as likely to reduce pruritus as was placebo (risk ratio 0.45; 95% CI, 0.37 to 0.58).
“A need exists for additional review studies, studies elucidating the pharmacology of SAMe, and clinical trials,” the authors write. “A better understanding of the risk benefit ratio of SAMe compared to conventional therapy, especially for depression and osteoarthritis, is very important. To that end, additional analysis of existing data could be done, but it would likely be more productive to support new definitive clinical studies to address this issue.”
Sept. 30, 2002
Reviewed by Gary D. Vogin, MD