title: Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants.
abstract: Given the proposed dopaminergic mechanism of low-dose naltrexone (LDN), we examined its efficacy as augmentation for depressive breakthrough on pro-dopaminergic antidepressant regimens.
  
  
  
  12 adults (67% female, mean age = 45±12) with recurrent DSM-IV major depressive disorder (MDD) on dopaminergic antidepressant regimens (stimulants, dopamine agonists, bupropion [≥300mg/day], aripiprazole [≤2.5mg/day], or sertraline [≥150mg/day]) were randomized to naltrexone 1mg b.i.d. (n=6) or placebo (n=6) augmentation for 3 weeks.
  
  
  
  All subjects completed the trial. Hamilton Depression Rating Scale (HAM-D-17) scores (primary outcome measure) decreased from 21.2±2.0 to 11.7±7.7 for LDN, from 23.7±2.3 to 17.8±5.9 for placebo (Cohen's d=0.62; p=0.3 between treatment groups). HAM-D-28 scores decreased from 26.2±4.0 to 12.0±9.8 for LDN, from 26.3±2.6 to 19.8±6.6 for placebo (d=1.15; p=0.097). Montgomery-Asberg Depression Rating Scale (MADRS-10 item) scores decreased from 30.4±4.9 to 12.2±8.4 for LDN, from 30.7±4.3 to 22.8±8.5) for placebo (d=1.45; p=0.035). MADRS-15 item scores decreased from 36.6±6.2 to 13.2±8.8 for LDN, from 36.7±4.2 to 26.0±10.0 for placebo (d=1.49; p=0.035). Clinical Global Improvement Scale-Severity (CGI-S) scores decreased from 4.3±0.5 to 3.0±1.1 for LDN, from 4.3±0.5 to 4.0±0.6 for placebo (d=1.22; p=0.064).
  
  
  
  Small study; restrictions on allowed antidepressants.
  
  
  
  LDN augmentation showed some benefit for MDD relapse on dopaminergic agents. Confirmation in larger studies is needed.
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, The Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States. Electronic address: dmischoulon@partners.org.
authors.forename: David
authors.initials: D
authors.lastname: Mischoulon
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, The Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Hylek
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, The Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States.
authors.forename: Albert S
authors.initials: AS
authors.lastname: Yeung
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, The Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States.
authors.forename: Alisabet J
authors.initials: AJ
authors.lastname: Clain
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, The Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States.
authors.forename: Lee
authors.initials: L
authors.lastname: Baer
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, The Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cusin
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, The Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States.
authors.forename: Dawn Flosnik
authors.initials: DF
authors.lastname: Ionescu
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, The Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Alpert
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, The Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States.
authors.forename: David P
authors.initials: DP
authors.lastname: Soskin
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, The Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D000068180:Aripiprazole / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D000697:Central Nervous System Stimulants; D009271:Naltrexone; D000068180:Aripiprazole; D020280:Sertraline
keywords: Breakthrough; Depression; LDN; Naltrexone; Relapse