SAMe for the Treatment of Depression and Osteoarthritis

Overview

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 osteoarthritis, depression, 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.

Findings

Researchers identified 102 relevant studies in the three selected areas: 47 studies for depression, 14 studies for osteoarthritis, and 41 studies for liver disease. The majority of the studies enrolled small numbers of patients, and the quality of the studies varied greatly, as judged by the Jadad criteria. Results are summarized in five evidence tables. After removal of duplicate studies, the distribution of studies across the three selected areas was as follows:

Out of 39 unique studies considered, 28 studies were included in a meta-analysis of the efficacy of SAMe to decrease symptoms of depression.

• Compared to placebo, treatment with SAMe was associated with an improvement of approximately 6 points in the score of the Hamilton Rating Scale for Depression measured at 3 weeks (95 percent CI [2.2, 9.0]). This degree of improvement is statistically as well as clinically significant and is equivalent to a partial response to treatment. Too few studies were available for which a risk ratio could be calculated for either a 25 percent or 50 percent improvement in the Hamilton Rating Scale for Depression. Therefore a pooled analysis could not be done, but the results generally favored SAMe compared to placebo.
• Compared to treatment with conventional antidepressant pharmacology, treatment with SAMe was not associated with a statistically significant difference in outcomes (risk ratios for a 25 and for a 50 percent decrease in the Hamilton Rating score for depression were 0.99 and 0.93, respectively; effect size for the Hamilton Rating score for depression measured continuously was 0.08 (95 percent CI [-0.17, -0.32])).

Out of 13 unique studies considered, 10 studies were included in a meta-analysis of the efficacy of SAMe to decrease pain of osteoarthritis.

• One large randomized clinical trial showed an effect size in favor of SAMe of 0.20 (95 percent CI [-0.39, - 0.02]) compared to placebo, thus demonstrating a decrease in the pain of osteoarthritis.
• Compared to treatment with nonsteroidal anti-inflammatory medication, treatment with SAMe was not associated with a statistically significant difference in outcomes (effect size 0.11; 95 percent CI [0.56, 0.35]).

Eight unique studies were included in a meta-analysis of the efficacy of SAMe to relieve pruritus and decrease elevated serum bilirubin levels associated with cholestasis of pregnancy.

• Compared to placebo, treatment with SAMe was associated with an effect size of nearly a full standard deviation (-0.95; 95 percent CI [-1.45, -0.45]) for decrease in pruritus and of over one and one-third standard deviations (-1.32; 95 percent CI [-1.76, -0.88]) for decrease in serum bilirubin levels.
• In two clinical trials that were not pooled, conventional therapy (ursodeoxycholic acid) was favored over SAMe for the treatment of pruritus. One of them was statistically significant. For serum bilirubin, the results of three small trials varied, and no conclusion could be drawn.

Out of 10 unique studies considered, six studies were included in a meta-analysis of the efficacy of SAMe to relieve pruritus and decrease elevated bilirubin levels associated with intrahepatic cholestasis caused by a variety of liver diseases.

• Compared to placebo, treatment with SAMe for pruritus was associated with a risk ratio of 0.45, meaning that patients treated with SAMe were twice as likely as placebo treated patients to have a reduction in pruritus (95 percent CI [0.37, 0.58]).
• Studies that compared SAMe to active therapy were insufficient in number to permit pooled analysis.

Twenty remaining studies were too heterogeneous with respect to both diagnosis (a wide variety of liver conditions) and outcomes to permit pooled analysis. They were assessed qualitatively.

S-Adenosyl-L-Methionine for Treatment of Depression, Osteoarthritis, and Liver Disease. Summary, Evidence Report/Technology Assessment: Number 64. AHRQ Publication No. 02-E033, August 2002. Agency for Healthcare Research and Quality, Rockville, MD