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Treatment of refractory obsessive–compulsive disorder with nutraceuticals (TRON): a 20-week, open label pilot study

Published online by Cambridge University Press:  21 June 2021

Jerome Sarris*
NICM Health Research Institute, Western Sydney University, Westmead, New South Wales, Australia The Melbourne Clinic, Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia
Gerard J. Byrne
University of Queensland Centre for Clinical Research, Royal Brisbane & Women’s Hospital, Brisbane, Queensland, Australia Mental Health Service, Royal Brisbane & Women’s Hospital, Brisbane, Queensland, Australia
Georgina Oliver
The Melbourne Clinic, Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia
Lachlan Cribb
The Melbourne Clinic, Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia
Scott Blair-West
The Melbourne Clinic, Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia
David Castle
Centre for Complex Interventions, Department of Psychiatry, University of Toronto
Olivia M. Dean
Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Barwon Health, Deakin University, Geelong, Victoria, Australia
David A. Camfield
Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Barwon Health, Deakin University, Geelong, Victoria, Australia
Vlasios Brakoulias
Western Sydney Local Health District Mental Health Service, Sydney, New South Wales, Australia School of Medicine, Blacktown Hospital, Translational Health Research Institute (THRI), Clinical and Health Psychology Research Initiative (CaHPRI), Western Sydney University, Sydney, New South Wales, Australia
Chad Bousman
Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada
Nathan Dowling
The Melbourne Clinic, Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia
Carolyn Ee
NICM Health Research Institute, Western Sydney University, Westmead, New South Wales, Australia
Jenifer Murphy
The Melbourne Clinic, Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia
Ranjit Menon
The Melbourne Clinic, Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia
Michael Berk
Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Barwon Health, Deakin University, Geelong, Victoria, Australia Florey Institute for Neuroscience and Mental Health, Melbourne, Victoria, Australia Orygen, The National Centre of Excellence in Youth Mental Health and the Centre for Youth Mental Health, Melbourne, Victoria, Australia
Suneel Chamoli
University of Queensland Centre for Clinical Research, Royal Brisbane & Women’s Hospital, Brisbane, Queensland, Australia
Mark Boschen
School of Applied Psychology, Griffith University, Gold Coast, Queensland, Australia
Chee H. Ng
The Melbourne Clinic, Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia
*Author for correspondence: Jerome Sarris, Email:



Obsessive–compulsive disorder (OCD) is often challenging to treat and resistant to psychological interventions and prescribed medications. The adjunctive use of nutraceuticals with potential neuromodulatory effects on underpinning pathways such as the glutamatergic and serotonergic systems is one novel approach.


To assess the effectiveness and safety of a purpose-formulated combination of nutraceuticals in treating OCD: N-acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-5′ phosphate, and selenium.


A 20-week open label proof-of-concept study was undertaken involving 28 participants with treatment-resistant DSM-5-diagnosed OCD, during 2017 to 2020. The primary outcome measure was the Yale-Brown Obsessive–Compulsive Scale (YBOCS), administered every 4 weeks.


An intention-to-treat analysis revealed an estimated mean reduction across time (baseline to week-20) on the YBOCS total score of −7.13 (95% confidence interval = −9.24, −5.01), with a mean reduction of −1.21 points per post-baseline visit (P ≤ .001). At 20-weeks, 23% of the participants were considered “responders” (YBOCS ≥35% reduction and “very much” or “much improved” on the Clinical Global Impression-Improvement scale). Statistically significant improvements were also revealed on all secondary outcomes (eg, mood, anxiety, and quality of life). Notably, treatment response on OCD outcome scales (eg, YBOCS) was greatest in those with lower baseline symptom levels, while response was limited in those with relatively more severe OCD.


While this pilot study lacks placebo-control, the significant time effect in this treatment-resistant OCD population is encouraging and suggests potential utility especially for those with lower symptom levels. Our findings need to be confirmed or refuted via a follow-up placebo-controlled study.

© The Author(s), 2021. Published by Cambridge University Press

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