N-Acetyl Cysteine (NAC) in the Treatment of Obsessive-Compulsive Disorder: A 16-Week, Double-Blind, Randomised, Placebo-Controlled Study

• Published in: CNS drugs Vol. 29; no. 9; pp. 801 - 809
• Main Authors: Sarris, Jerome, Oliver, Georgina, Camfield, David A., Dean, Olivia M., Dowling, Nathan, Smith, Deidre J., Murphy, Jenifer, Menon, Ranjit, Berk, Michael, Blair-West, Scott, Ng, Chee H.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.09.2015; Springer Nature B.V
• Subjects: Acetylcysteine - therapeutic use; Adolescent; Adult; Aged; Analysis of Variance; Autism; Behavior; Brain research; Clinical trials; Double-Blind Method; Female; Follow-Up Studies; Free Radical Scavengers; Funding; Humans; Male; Medical research; Medicine; Medicine & Public Health; Mental disorders; Middle Aged; Neurology; Neurosciences; Neuroses; Obsessive compulsive disorder; Obsessive-Compulsive Disorder - drug therapy; Oxidative stress; Pharmaceutical industry; Pharmacotherapy; Psychiatric Status Rating Scales; Psychiatry; Psychopharmacology; Retrospective Studies; Schizophrenia; Scholarships & fellowships; Short Communication; Time Factors; Treatment Outcome; Young Adult; Hamilton Anxiety Rate Scale; Trichotillomania; Pathological Gambling; Subcortical Brain Region; Obsessive Compulsive Spectrum Disorder
• ISSN: 1172-7047; 1179-1934
• DOI: 10.1007/s40263-015-0272-9

Background Obsessive-compulsive disorder (OCD) is a disabling mental illness for which pharmacological and psychosocial interventions are all too often inadequate. Recent preclinical and clinical studies have implicated dysfunction of glutamatergic neurotransmission in the pathophysiology of OCD. The amino acid-based nutraceutical N -acetyl cysteine (NAC) is a safe and readily available agent that has been found to modify the synaptic release of glutamate in subcortical brain regions via modulation of the cysteine-glutamate antiporter. Objective The aim of this study was to assess the efficacy and safety of NAC in treating OCD. Methods A 16-week, double-blind, placebo-controlled, randomised trial using 3 g/day of NAC (1.5 g twice daily) in 44 participants (aged 18–70 years) with Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)-diagnosed OCD, during 2013–2015. The primary outcome measure was the Yale–Brown Obsessive Compulsive Scale (YBOCS), conducted every 4 weeks. Results Analysis of the full sample (intention-to-treat) with repeated measures mixed linear modelling revealed a nonsignificant time × treatment interaction for the YBOCS scale total score ( p  = 0.39). A per-protocol analysis removing protocol violators also failed to show a significant time × treatment interaction for YBOCS total score ( p  = 0.15). However, a significant time × treatment interaction was observed for the YBOCS ‘Compulsions’ subscale in favour of NAC ( p  = 0.013), with a significant reduction observed at week 12 (dissipating at week 16). At 16 weeks, only four (20 %) participants were considered ‘responders’ (YBOCS ≥35 % reduction at endpoint) versus four (27 %) in the placebo group. The NAC was well-tolerated, aside from more cases of heartburn occurring compared with placebo ( p  = 0.045). Conclusion Further research involving NAC for OCD may require larger samples to detect moderate or small effect sizes, involve dosage or formulation differences, use in concert with exposure therapy, or an additional post-study observational period to mitigate study withdrawal. Trial Registration ACTRN12613000310763.