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. Obsessive-compulsive disorder (OCD) causes unwanted thoughts and repetitive behaviors that interfere with daily life. Standard medications, such as sertraline, help some patients, but many continue to struggle. This study tests whether adding N-acetylcysteine (NAC), a natural dietary supplement, to standard medication could improve outcomes. We randomly assigned 35 adults with moderate to severe OCD to receive sertraline plus NAC or sertraline plus placebo for 12 weeks. People receiving NAC experienced faster relief from obsessive thoughts compared to those taking placebo, with 100% of NAC patients achieving meaningful improvement versus 92.6% in the placebo group. NAC appears safe and may accelerate symptom relief when combined with standard medication, offering patients a potential low-risk option for faster improvement in their symptoms. Askari, Eghdami, et al. conduct a 12-week double-blind randomized trial testing adjunctive N-acetylcysteine versus placebo added to fixed-dose sertraline in adults with moderate to severe OCD. Adjunctive N-acetylcysteine yields faster and greater obsession symptom reduction than placebo, and is well tolerated, without adding cognitive benefit.