S-adenosylmethionine (SAMe) as treatment for depression: a systematic review

Clin Invest Med. 2005 Jun;28(3):132-9.


Purpose: To assess the evidence evaluating S-adenosylmethionine (SAMe) supplementation as treatment for depression.

Methods: Searches of Medline, Psychinfo, AMED, and Cochrane Controlled Trials Register were conducted from database inception through September 2001. Randomized controlled trials, controlled clinical trials, intervention studies, case-control studies, reviews, and case reports examining the evidence behind S-adenosylmethionine (SAMe) supplementation in depression among humans were selected. No limits were placed on study populations for demographics or co-morbidities. Only English language papers were abstracted and assessed for trial quality. Two abstractors independently evaluated each study, and then reconciled findings. As data were available, between group treatment effect size was noted or, as needed, calculated.

Results: Eleven articles met initial inclusion criteria; five intervention trials, two RCTs, two reviews, one controlled clinical trial, and one meta-analysis. Using the one common outcome measure among all the intervention studies and RCTs, the Hamilton Rating Scale for Depression, direct comparison of effect sizes was made. A favourable and significant between group effect was seen.

Conclusion: All of the studies reviewed were short term, making translation to the clinical setting difficult. However, there appears to be a role for SAMe in the treatment of major depression in adults. Questions remain about mechanism of action, bioavailability, and absorption of oral SAMe. Further study of SAMe as independent and adjuvant therapy for major depression in adults is indicated.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Clinical Trials as Topic
  • Databases, Bibliographic
  • Depression / drug therapy*
  • Humans
  • S-Adenosylmethionine / pharmacology*
  • Time Factors
  • Treatment Outcome


  • S-Adenosylmethionine