N-acetyl cysteine (NAC) augmentation in the treatment of obsessive-compulsive disorder: A phase III, 20-week, double-blind, randomized, placebo-controlled trial

Jerome Sarris; Gerard Byrne; David Castle; Chad Bousman; Georgina Oliver; Lachlan Cribb; Scott Blair-West; Vlasios Brakoulias; David Camfield; Carolyn Ee; Suneel Chamoli; Mark Boschen; Olivia M Dean; Nathan Dowling; Ranjit Menon; Jenifer Murphy; Najwa-Joelle Metri; Thomas P Nguyen; Andrew Wong; Rebecca Jordan; Diana Karamacoska; Susan L Rossell; Michael Berk; Chee H Ng

doi:10.1016/j.pnpbp.2022.110550

N-acetyl cysteine (NAC) augmentation in the treatment of obsessive-compulsive disorder: A phase III, 20-week, double-blind, randomized, placebo-controlled trial

Prog Neuropsychopharmacol Biol Psychiatry. 2022 Jul 13:117:110550. doi: 10.1016/j.pnpbp.2022.110550. Epub 2022 Mar 15.

Authors

Jerome Sarris¹, Gerard Byrne², David Castle³, Chad Bousman⁴, Georgina Oliver⁵, Lachlan Cribb⁵, Scott Blair-West⁵, Vlasios Brakoulias⁶, David Camfield⁷, Carolyn Ee⁸, Suneel Chamoli⁹, Mark Boschen¹⁰, Olivia M Dean¹¹, Nathan Dowling⁵, Ranjit Menon⁵, Jenifer Murphy⁵, Najwa-Joelle Metri⁸, Thomas P Nguyen¹², Andrew Wong⁸, Rebecca Jordan⁸, Diana Karamacoska⁸, Susan L Rossell¹³, Michael Berk¹⁴, Chee H Ng⁵

Affiliations

¹ NICM Health Research Institute, Western Sydney University, Westmead, NSW, Australia; Florey Institute for Neuroscience and Mental Health, Kenneth Myer Building, Royal Parade, Parkville, Melbourne, Victoria, Australia; Professorial Unit, The Melbourne Clinic, Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia. Electronic address: j.sarris@westernsydney.edu.au.
² University of Queensland Centre for Clinical Research, Royal Brisbane & Women's Hospital, Brisbane, Australia; Mental Health Service, Royal Brisbane & Women's Hospital, Brisbane, Australia.
³ Department of Psychiatry, University of Melbourne, Melbourne, Australia; Department of Psychiatry, St Vincent's Hospital, Melbourne, Australia.
⁴ Departments of Medical Genetics, Psychiatry, Physiology & Pharmacology, and Community Health Sciences, University of Calgary, Calgary, AB, Canada.
⁵ Professorial Unit, The Melbourne Clinic, Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia.
⁶ Western Sydney Local Health District Mental Health Service, Sydney, Australia; Translational Health Research Institute, Western Sydney University, Sydney, NSW, Australia; School of Medicine, Western Sydney University, Australia.
⁷ Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia.
⁸ NICM Health Research Institute, Western Sydney University, Westmead, NSW, Australia.
⁹ University of Queensland Centre for Clinical Research, Royal Brisbane & Women's Hospital, Brisbane, Australia.
¹⁰ School of Applied Psychology, Griffith University, Gold Coast, Australia.
¹¹ Florey Institute for Neuroscience and Mental Health, Kenneth Myer Building, Royal Parade, Parkville, Melbourne, Victoria, Australia; Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia.
¹² NICM Health Research Institute, Western Sydney University, Westmead, NSW, Australia; School of Medicine, Western Sydney University, Australia.
¹³ Centre for Mental Health, Swinburne University of Technology, Melbourne, VIC, Australia; Department of Mental Health, St Vincent's Hospital, Melbourne, VIC, Australia.
¹⁴ Florey Institute for Neuroscience and Mental Health, Kenneth Myer Building, Royal Parade, Parkville, Melbourne, Victoria, Australia; Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Orygen, The National Centre of Excellence in Youth Mental Health and the Centre for Youth, Mental Health Parkville, Melbourne, Victoria, Australia.

PMID: 35304155
DOI: 10.1016/j.pnpbp.2022.110550

Abstract

Objective: Preliminary evidence has suggested that adjunctive N-acetylcysteine (NAC), an antioxidant precursor to glutathione, may reduce symptoms of obsessive-compulsive disorder (OCD). We conducted a 20-week, multi-site, randomized controlled trial to investigate the safety and efficacy of the adjunctive use of NAC in OCD.

Methods: The study was a phase III, 20-week, double-blind, randomized controlled trial across multiple sites in Australia investigating 2 g to 4 g per day of NAC (titrated according to response) in 98 participants with DSM-5 diagnosed OCD. Data were analysed using linear mixed effects models for the 89 participants who attended at least one follow-up visit.

Results: A modified intention-to-treat analysis of the primary outcome found no evidence that NAC reduced symptoms of OCD measured on the Yale-Brown Obsessive-Compulsive Scale, relative to placebo (mean difference at week 20 = 0.53, 95% compatibility interval = -2.18, 3.23; p = 0.70; favouring placebo). There was also no evidence that NAC, compared to placebo, improved outcomes on the secondary measures including anxiety, depression, quality of life, functioning, or clinician/participant impression. NAC was well-tolerated with only mild gastrointestinal adverse events associated with the treatment.

Conclusion: We found no evidence supporting the efficacy of the adjunctive use of NAC in OCD.

Keywords: Anxiety; Clinical trial; Nutraceutical; Obsessive compulsive disorder; Oxidative stress.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Acetylcysteine* / therapeutic use
Double-Blind Method
Humans
Obsessive-Compulsive Disorder* / therapy
Quality of Life
Treatment Outcome

Substances

Acetylcysteine