Randomized, Double-Blind, Placebo-Controlled Trial of <em>N</em>-Acetylcysteine Augmentation for Treatment-Resistant Obsessive-Compulsive Disorder

Objective: To evaluate the efficacy of serotonin reuptake inhibitor (SRI) augmentation with N-acetylcysteine (NAC), a glutamate modulator and antioxidant medication, for treatment-resistant obsessive-compulsive disorder (OCD).

Methods: We conducted a randomized, double-blind, placebo-controlled, 16-week trial of NAC (3,000 mg daily) in adults (aged 18–65 years) with treatment-resistant OCD, established according to DSM-IV criteria. Forty subjects were recruited at an OCD-specialized outpatient clinic at a tertiary hospital (May 2012–October 2014). The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores. To evaluate the variables group, time, and interaction effects for Y-BOCS scores at all time points, we used nonparametric analysis of variance with repeated measures. Secondary outcomes were the severity scores for anxiety, depression, specific OCD symptom dimensions, and insight.

Results: Both groups showed a significant reduction of baseline Y-BOCS scores at week 16: the NAC group had a reduction of 4.3 points (25.6 to 21.3), compared with 3.0 points (24.8 to 21.8) for the placebo group. However, there were no significant differences between groups (P = .92). Adding NAC was superior to placebo in reducing anxiety symptoms (P = .02), but not depression severity or specific OCD symptom dimensions. In general, NAC was well tolerated, despite abdominal pain being more frequently reported in the NAC group (n [%]: NAC = 9 [60.0], placebo = 2 [13.3]; P < .01).

Conclusions: Our trial did not demonstrate a significant benefit of NAC in reducing OCD severity in treatment-resistant OCD adults. Secondary analysis suggested that NAC might have some benefit in reducing anxiety symptoms in treatment-resistant OCD patients.

Trial Registration: ClinicalTrials.gov identifier: NCT01555970

J Clin Psychiatry 2017;78(7):e766–e773

https://doi.org/10.4088/JCP.16m11101