N-Acetyl Cysteine (NAC) in the Treatment of Obsessive-Compulsive Disorder: A 16-Week, Double-Blind, Randomised, Placebo-Controlled Study
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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.
The aim of this study was to assess the efficacy and safety of NAC in treating OCD.
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.
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).
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.
KeywordsPathological Gambling Trichotillomania Hamilton Anxiety Rate Scale Subcortical Brain Region Obsessive Compulsive Spectrum Disorder
The NAC was kindly donated and supplied by Bioceuticals®, Alexandria, NSW, Australia. Jerome Sarris is funded by a CR Roper Fellowship, and Michael Berk is supported by a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship 1059660.
Compliance with Ethical Standards
This study was given ethics approval by The Melbourne Clinic Ethics Committee (TMC_HREC no. 219), which is an NHMRC registered Ethics Committee in Australia, and was conducted according to the 1964 Declaration of Helsinki. All participants freely gave informed consent before commencing the study.
No funding was received for the conduct of this study or the preparation of this manuscript. The NAC and placebo tablets were supplied free of charge by Bioceuticals (this company does not currently sell this product; additionally, they had no involvement in study design/conduct/data analysis/publication of results).
Conflict of interest
No specific conflicts are identified from any individual author. Jerome Sarris has received honoraria, research support, royalties, and consultancy or travel grant funding from Bioceuticals, Blackmores, Taki Mai, Integria Health Pepsico, HealthEd, Soho-Flordis, Pfizer, Elsevier, the Society for Medicinal Plant and Natural Product Research, CR Roper Fellowship, The NHMRC, and Chaminade University. Olivia M. Dean is a Research Fellow and has received grant support from the Brain and Behavior Foundation, Simons Autism Foundation, Australian Rotary Health, Stanley Medical Research Institute, Deakin University, Brazilian Society Mobility Program, Lilly, NHMRC and an Australasian Society for Bipolar Disorders/Servier grant. She has also received in-kind support from BioMedica Nutraceuticals, Nutrition Care and Bioceuticals. Chee Ng has previously received research support from Wyeth and Lundbeck, and speaker honoraria from Servier, Bristol-Myers Squibb, Organon, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Astra-Zenaca, Wyeth, and Pfizer. Michael Berk has received grant/research support from the National Institutes of Health, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Meat and Livestock Board, Organon, Novartis, Mayne Pharma, Servier and Woolworths, has been a speaker for Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth, and served as a consultant to Astra-Zeneca, Bioadvantex, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck Merck and Servier, and is a co-inventor on two provisional patents regarding the use of NAC and related compounds for psychiatric indications assigned to the Mental Health Research Institute. Georgina Oliver, David A. Camfield, Nathan Dowling, Deidre J. Smith, Jenifer Murphy, Ranjit Menon, and Scott Blair-West have no conflicts of interest to declare.
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