Clinical symptoms and cognitive functioning following adjunctive N-acetylcysteine in obsessive-compulsive disorder: a double-blind, placebo-controlled trial

Obsessive-compulsive disorder (OCD) often remains partially responsive to first-line treatments such as selective serotonin reuptake inhibitors (SSRI). N-acetylcysteine (NAC), a glutamate-modulating antioxidant, has shown promise as an adjunctive therapy, but prior studies frequently lacked standardized pharmacotherapy and cognitive outcome measures, particularly in Iranian populations.

In this 12-week, double-blind, placebo-controlled randomized clinical trial (IRCT20170123032145N7, registered on 2023-06-08), 35 adults with moderate to severe OCD were assigned to receive sertraline (200 mg/day) augmented with either NAC (2400 mg/day) or placebo. Clinical symptoms were assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at baseline, weeks 4, 8, and 12. Cognitive functioning was evaluated before and after treatment using the Wisconsin Card Sorting Test and the D2 Test of Attention.

This pilot study reveals a significant Time × Group interaction for Y-BOCS Total (p < 0.005), with the NAC group showing greater symptom reduction than placebo. The Obsession subscale demonstrates the strongest effect (p < 0.001), while Compulsion subscale improvements are comparable between groups. Clinical response rate ( ≥ 35% Y-BOCS reduction) is significantly higher in the NAC group (100%) versus placebo (92.6%, p = 0.004). Both groups improve on cognitive measures (processing speed and attention) over time, with no significant between-group differences. Adverse events are mild and comparable.

Adjunctive NAC may enhance early clinical response in OCD, particularly for obsessions, when added to high-dose SSRI (Sertraline) treatment. However, no cognitive advantage is observed within the 12-week period. These preliminary findings support NAC’s safety and potential utility as a short-term adjunctive treatment in OCD.