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S-Adenosylmethionine (SAMe) monotherapy for depression: an 8-week double-blind, randomised, controlled trial

Psychopharmacology, ISSN: 1432-2072, Vol: 237, Issue: 1, Page: 209-218
2020
  • 26
    Citations
  • 0
    Usage
  • 67
    Captures
  • 0
    Mentions
  • 1
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    26
  • Captures
    67
  • Social Media
    1
    • Shares, Likes & Comments
      1
      • Facebook
        1

Article Description

Rationale: Dysregulation of the one carbon cycle is documented in depression. Thereby, S-adenosylmethionine (SAMe), a one–carbon cycle nutraceutical compound with a favourable side effect profile, has a theoretical rationale for efficacy. However, further controlled studies are required to confirm SAMe’s efficacy. Objectives: To test the efficacy of SAMe versus placebo in unmedicated DSM-5 diagnosed (major depressive disorder) (MDD) patients with mild-to-moderate levels of depressive symptoms. Methods: We conducted an 8-week, double-blind, randomised controlled trial testing 800 mg/day of SAMe monotherapy versus placebo in 49 patients with MDD (Montgomery-Åsberg Depression Rating Scale [MADRS] score 14–25) who were not currently taking antidepressants. One–carbon cycle biomarkers, brain-derived neurotropic factor (BDNF), and relevant single nucleotide polymorphisms (SNPs) were analysed as potential treatment moderators. Results: A clinically relevant differential reduction from baseline to week 8 of 3.76 points occurred on the primary outcome (MADRS) in favour of SAMe. This however was not significant (p = 0.13) on an adjusted linear mixed model, notwithstanding a medium to large effect size of 0.72. A high placebo response rate of 53% occurred (> 50% reduction on MADRS). Exploratory analyses showed that SAMe was however effective in reducing depression amongst participants with milder depression severity (MADRS ≤ 22, p = 0.045). Response was not moderated by BDNF, SNPs, or one–carbon cycle biomarkers, although increased folate concentrations were correlated with improved symptoms in the SAMe group (r = − 0.57, p = 0.026). The treatment was safe and well tolerated. Conclusions: Although a differential reduction in depression symptoms between groups was observed in favour of SAMe, the results of this pilot study were not statistically significant. Trial registration: ANZCTR—Australian New Zealand Clinical Trials Registry; No.: ACTRN12613001299796; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364900.

Bibliographic Details

Sarris, Jerome; Murphy, Jenifer; Stough, Con; Mischoulon, David; Bousman, Chad; MacDonald, Patricia; Adams, Laura; Nazareth, Sonia; Oliver, Georgina; Cribb, Lachlan; Savage, Karen; Menon, Ranjit; Chamoli, Suneel; Berk, Michael; Ng, Chee H; Byrne, Gerard J

Springer Science and Business Media LLC

Pharmacology, Toxicology and Pharmaceutics

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