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.