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SAMe for Treatment of Depression

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.

Future Research

The review has identified a number of promising areas for future research. These areas are discussed briefly.

A need exists for additional review studies, studies elucidating the pharmacology of SAMe, and clinical trials. 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.

Good dose-escalation studies have not been performed using the oral formulation of SAMe for depression, osteoarthritis, or liver disease. Once efficacy of the most effective oral dose of SAMe has been demonstrated, larger clinical trials are indicated for the use of SAMe for depression, osteoarthritis, and cholestasis. Such trials would need to enroll large numbers of patients with homogeneous diagnoses, and focus on significant clinical outcomes. Ideally, they would compare SAMe to both placebo and standard care. Information on side effects and adverse events should be systematically collected in these trials.

For liver conditions other than cholestasis, additional smaller trials should be conducted to ascertain which patient populations would benefit most from SAMe, and what interventions (dose and route of administration) are most effective. Additional smaller clinical trials of an exploratory nature should be conducted to investigate uses of SAMe to decrease the latency of effectiveness of conventional antidepressants and to treat of postpartum depression.

Source: The National Center for Complementary and Alternative Medicine at the National Institutes of Health. Current as of August 2002.

next: St. John's Wort and the Treatment of Depression
~ depression library articles
~ all articles on depression

Last Updated: 23 June 2016
Reviewed by Harry Croft, MD

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