title: N-Acetyl Cysteine (NAC) in the Treatment of Obsessive-Compulsive Disorder: A 16-Week, Double-Blind, Randomised, Placebo-Controlled Study.
abstract: 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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ACTRN12613000310763.
authors.affiliation: Department of Psychiatry, The Melbourne Clinic, The University of Melbourne, 2 Salisbury St, Richmond, Melbourne, VIC, 3121, Australia. jsarris@unimelb.edu.au.|Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC, Australia. jsarris@unimelb.edu.au.
authors.forename: Jerome
authors.initials: J
authors.lastname: Sarris
authors.affiliation: Department of Psychiatry, The Melbourne Clinic, The University of Melbourne, 2 Salisbury St, Richmond, Melbourne, VIC, 3121, Australia.
authors.forename: Georgina
authors.initials: G
authors.lastname: Oliver
authors.affiliation: Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC, Australia.|Illawarra Health and Medical Research Institute, Wollongong, NSW, Australia.|School of Psychology, University of Wollongong, Wollongong, NSW, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Camfield
authors.affiliation: IMPACT Strategic Research Centre, School of Medicine, Deakin University, Barwon Health, Geelong, VIC, Australia.|Florey Institute for Neuroscience and Mental Health, Melbourne, VIC, Australia.
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Dean
authors.affiliation: Department of Psychiatry, The Melbourne Clinic, The University of Melbourne, 2 Salisbury St, Richmond, Melbourne, VIC, 3121, Australia.
authors.forename: Nathan
authors.initials: N
authors.lastname: Dowling
authors.affiliation: Department of Psychiatry, The Melbourne Clinic, The University of Melbourne, 2 Salisbury St, Richmond, Melbourne, VIC, 3121, Australia.
authors.forename: Deidre J
authors.initials: DJ
authors.lastname: Smith
authors.affiliation: Department of Psychiatry, The Melbourne Clinic, The University of Melbourne, 2 Salisbury St, Richmond, Melbourne, VIC, 3121, Australia.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Murphy
authors.affiliation: Department of Psychiatry, The Melbourne Clinic, The University of Melbourne, 2 Salisbury St, Richmond, Melbourne, VIC, 3121, Australia.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Menon
authors.affiliation: IMPACT Strategic Research Centre, School of Medicine, Deakin University, Barwon Health, Geelong, VIC, Australia.|Orygen, The National Centre of Excellence in Youth Mental Health and the Centre for Youth Mental Health, Melbourne, VIC, Australia.|Florey Institute for Neuroscience and Mental Health, Melbourne, VIC, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.affiliation: Department of Psychiatry, The Melbourne Clinic, The University of Melbourne, 2 Salisbury St, Richmond, Melbourne, VIC, 3121, Australia.
authors.forename: Scott
authors.initials: S
authors.lastname: Blair-West
authors.affiliation: Department of Psychiatry, The Melbourne Clinic, The University of Melbourne, 2 Salisbury St, Richmond, Melbourne, VIC, 3121, Australia.
authors.forename: Chee H
authors.initials: CH
authors.lastname: Ng
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D016166:Free Radical Scavengers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy*; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016166:Free Radical Scavengers; D000111:Acetylcysteine