title: S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: efficacy and effects of histamine and carnitine as moderators of response.
abstract: OBJECTIVE
  To assess the antidepressant efficacy of S-adenosyl methionine (SAMe), a naturally occurring methyl donor, versus the selective serotonin reuptake inhibitor (SSRI) escitalopram and a placebo control; and to determine whether serum histamine or carnitine levels modified treatment response.
  
  
  METHODS
  We examined a subsample (n=144) from one site of a two-site study of adults with diagnosed Major Depressive Disorder (MDD), recruited from 4/13/05 to 12/22/09, who consented to the additional blood draw for serum histamine and carnitine levels. After washout, eligible subjects were randomized to SAMe (1600-3200mg/daily), escitalopram (10-20mg/daily), or matching placebo for 12 weeks of double-blind treatment (titration at week 6 in non-response).
  
  
  RESULTS
  On the primary outcome of the Hamilton Depression Rating Scale (HAMD-17), a significant difference in improvement was observed between groups from baseline to week 12 (p=0.039). The effect size from baseline to endpoint was moderate to large for SAMe versus placebo (d=0.74). SAMe was superior to placebo from week 1, and to escitalopram during weeks 2, 4, and 6. No significant effect was found between escitalopram and placebo or SAMe. Response rates (HAMD-17≥50% reduction) at endpoint were 45%, 31%, and 26% for SAMe, escitalopram, and placebo, respectively; while remission rates (HAM-D≤7) were 34% for SAMe (p=0.003), 23% for escitalopram (p=0.023), and 6% for placebo. No correlation between baseline histamine level and reduction of HAMD-17 score was found for either the SAMe or escitalopram groups. Baseline carnitine levels were also not found to moderate response to either treatment.
  
  
  CONCLUSIONS
  While SAMe appears to be an effective antidepressant agent, the overall findings from the parent study (which showed no significant difference between groups due to site differences) must be taken into consideration.
  
  
  CONCLUSIONS
  These preliminary results provide encouraging evidence for the use of SAMe in the treatment of MDD. Histamine and carnitine serum level may not necessarily moderate response to SAMe.
authors.affiliation: The University of Melbourne, Department of Psychiatry, Australia; Swinburne University of Technology, Centre for Human Psychopharmacology, Australia. Electronic address: jsarris@unimelb.edu.au.
authors.forename: Jerome
authors.initials: J
authors.lastname: Sarris
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, United States.
authors.forename: George I
authors.initials: GI
authors.lastname: Papakostas
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, United States.
authors.forename: Ottavio
authors.initials: O
authors.lastname: Vitolo
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, United States.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, United States.
authors.forename: David
authors.initials: D
authors.lastname: Mischoulon
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002331:Carnitine / Q000097:blood*; D015283:Citalopram / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006632:Histamine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012436:S-Adenosylmethionine / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D002331:Carnitine; D015283:Citalopram; D006632:Histamine; D012436:S-Adenosylmethionine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Carnitine; Depression; Histamine; One-carbon cycle; RCT; S-adenosyl methionine