N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial

J Clin Psychopharmacol. 2012 Dec;32(6):797-803. doi: 10.1097/JCP.0b013e318272677d.


Objective: This study aimed to evaluate the efficacy and safety of N-acetylcysteine, a glutamate-modulating agent, in patients with treatment-refractory obsessive-compulsive disorder as an adjunct to serotonin reuptake inhibitor treatment.

Methods: Forty-eight patients (36 women; mean ± SD age, 30.93 ± 4.99) with obsessive-compulsive disorder who failed to respond to a course of serotonin reuptake inhibitor treatment were randomized to a 12-week intervention period of N-acetylcysteine (up to 2400 mg/d) or placebo. Primary outcome measures were the change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score from baseline to end point and the rate of full response in each group at the end of trial. Full response was defined as 35% or greater reduction in Y-BOCS score from baseline.

Results: Changes of Y-BOCS score were different over time (P < 0.001) and between groups (P < 0.001). N-acetylcysteine-assigned patients showed significantly improved mean Y-BOCS score (P = 0.003) and Clinical Global Impression-Severity of Illness scale score (P = 0.01) but not Clinical Global Impression-Improvement scale score at study end point. Of the patients in the N-acetylcysteine group, 52.6% were full responders at the end of the study, which was significantly higher than 15% of the patients in the placebo group (P = 0.013).

Conclusion: This trial suggests that N-acetylcysteine may be a safe and effective option to augment standard treatment in patients with refractory obsessive-compulsive disorder.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acetylcysteine / administration & dosage*
  • Adult
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Obsessive-Compulsive Disorder / drug therapy*
  • Obsessive-Compulsive Disorder / epidemiology
  • Obsessive-Compulsive Disorder / psychology*
  • Serotonin Uptake Inhibitors / administration & dosage*
  • Treatment Outcome
  • Young Adult


  • Serotonin Uptake Inhibitors
  • Acetylcysteine