A double-blind, randomized, placebo-controlled clinical trial of S-adenosyl-L-methionine (SAMe) versus escitalopram in major depressive disorder

J Clin Psychiatry. 2014 Apr;75(4):370-6. doi: 10.4088/JCP.13m08591.

Abstract

Objective: To examine the comparative antidepressant efficacy of S-adenosyl-L-methionine (SAMe) and escitalopram in a placebo-controlled, randomized, double-blind clinical trial.

Method: One hundred eighty-nine outpatients (49.7% female, mean [SD] age = 45 [15] years) with DSM-IV-diagnosed major depressive disorder (MDD) were recruited from April 13, 2005, to December 22, 2009, at the Massachusetts General Hospital and at Butler Hospital. Patients were randomized for 12 weeks to SAMe 1,600-3,200 mg/d, escitalopram 10-20 mg/d, or placebo. Doses were escalated at 6 weeks in the event of nonresponse. The main outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS-17). Tolerability was assessed by the Systematic Assessment for Treatment of Emergent Events-Specific Inquiry (SAFTEE-SI).

Results: All 3 treatment arms demonstrated a significant improvement of about 5-6 points in HDRS-17 scores (P < .001 for all), and no significant differences were observed between the treatment arms (P > .05 for all). Response rates in the intent-to-treat sample were 36% for SAMe, 34% for escitalopram, and 30% for placebo. Remission rates were 28% for SAMe, 28% for escitalopram, and 17% for placebo. No comparisons between treatment groups attained significance (P > .05 for all). Tolerability was good, with gastrointestinal side effects (19% for stomach discomfort and 20% for diarrhea) as the most common in the SAMe arm. Significant differences were observed between treatment groups for dizziness, anorgasmia, diminished mental acuity, and hot flashes (P < .05 for all).

Conclusions: The results fail to support an advantage over placebo for either the investigational treatment SAMe or the standard treatment escitalopram for MDD.

Trial registration: ClinicalTrials.gov identifier: NCT00101452.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / therapeutic use*
  • Citalopram / therapeutic use*
  • Depressive Disorder, Major / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • S-Adenosylmethionine / therapeutic use*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Antidepressive Agents
  • Serotonin Uptake Inhibitors
  • Citalopram
  • S-Adenosylmethionine

Associated data

  • ClinicalTrials.gov/NCT00101452