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NIH analysis of SAMe for the treatment of depression indicates SAMe does decrease symptoms of depression.

The objective of this report was to conduct a search of the published literature on the use of S-adenosyl- L-methionine (SAMe) for the treatment of depression, osteoarthritis, and liver disease; and, on the basis of that search, to evaluate the evidence for the efficacy of SAMe. A broad search revealed sufficient literature to support a detailed review of the use of SAMe for three conditions: depression, osteoarthritis, and cholestasis of pregnancy and intrahepatic cholestasis associated with liver disease.

Depression will affect 10 to 25 percent of women and 5 to 12 percent of men in the United States during their lifetimes. Approximately 10 to 15 million people experience clinical depression in any given year. The annual cost for treatment and lost wages is estimated at $43.7 to $52.9 billion.

Osteoarthritis is the most common form of arthritis. An estimated 15 percent of Americans suffer from arthritis, and the annual cost to society is estimated at $95 billion. It is the second most common cause cited in claims for Social Security disability benefits.

Intrahepatic cholestasis of pregnancy occurs in 1 in 500 to 1000 pregnancies and is associated with an increased risk of premature delivery and fetal death. Intrahepatic cholestasis is a relatively common complication of a number of acute and chronic liver diseases such as viral hepatitis, alcoholic hepatitis, and autoimmune liver diseases. In two series of chronic liver disease patients, 35 percent had intrahepatic cholestasis characterized by elevations of bilirubin and liver enzymes. While an economic cost is difficult to assign to cholestasis, pruritus causes significant morbidity in affected patients.

Empirical evidence of the efficacy of SAMe for the treatment of these three conditions would be helpful to health care providers who manage them and would be useful in identifying areas for future research.

Reporting the Evidence

NIH analysis of SAMe for the treatment of depression indicates SAMe does decrease symptoms of depression. Read more.Searches of the literature yielded 1,624 titles, of which 294 were selected to review; the latter included meta-analyses, clinical trials, and reports that contained supplemental information on SAMe. Ninety-nine articles, representing 102 individual studies, met the screening criteria. They focused on SAMe treatment for depression, osteoarthritis, or liver disease and presented data from clinical trials on humans. Of these 102 studies, 47 focused on depression, 14 focused on osteoarthritis, and 41 focused on liver disease (all conditions).


A panel of technical experts representing diverse disciplines was established to advise the researchers throughout the research. In consultation with the funding agencies and taking into account the uses for which SAMe was generally recommended, the use of SAMe to treat depression, osteoarthritis, and liver disease was selected as the focus of the report. The aim was to perform a meta-analysis whenever the literature was appropriate for such an analysis.

Search Strategy

Twenty-five biomedical databases were searched through year 2000: MEDLINE®, HealthSTAR, EMBASE, BIOSIS Previews®, MANTIS, Allied and Complementary Medicine, Cochrane™ Library, CAB HEALTH, BIOBASE, SciSearch®, PsychINFO, Mental Health Abstracts, Health News Daily, PASCAL, TGG Health & Wellness DB, and several pharmaceutical databases. The researchers searched using the term SAMe and its many pharmacological synonyms, the three focus disease states, study design, and article type. They also searched the bibliographies of review and meta-analysis articles and questioned experts to identify additional citations. An additional 62 articles were identified from these sources, particularly from review articles and from citations suggested by the advisors.

Selection Criteria

Reports were included in the synthesis of evidence if they focused on SAMe for one of the selected diseases and presented the results of randomized clinical trials on human subjects. Language of publication was not a barrier to inclusion. About 25 percent of the selected studies were in foreign languages, mainly Italian.

Data Collection and Analysis

All selected titles, abstracts, and articles, in all languages, were reviewed independently by two reviewers who were fluent in the appropriate language, and all disagreements were resolved by consensus. Information was collected about patient demographics, disease state, intervention, study design, and outcomes. Sufficient numbers of homogeneous studies existed to permit a meta-analysis of the efficacy of SAMe for treatment of four conditions: depression versus placebo and active (pharmacological) therapy, osteoarthritis versus placebo and active (pharmacological) therapy, cholestasis of pregnancy versus placebo and active therapy, and intrahepatic cholestasis associated with liver disease versus placebo. The remainder of the liver disease studies were too heterogeneous for pooled analysis and were assessed qualitatively.