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Cognitive effects of adjunctive N-acetyl cysteine in psychosis

Published online by Cambridge University Press:  29 November 2016

M. Rapado-Castro
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain Department of Psychiatry, Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, 161 Barry Street, Carlton South, Victoria, Australia Orygen, The National Centre of Excellence in Youth Mental Health, Victoria, Australia
S. Dodd
Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, PO Box 291, Geelong, Victoria,Australia Department of Psychiatry, University of Melbourne, Level 1 North, Main Block, Royal Melbourne Hospital, Parkville, Victoria,Australia
A. I. Bush
Department of Psychiatry, University of Melbourne, Level 1 North, Main Block, Royal Melbourne Hospital, Parkville, Victoria,Australia
G. S. Malhi
Academic Department of Psychiatry, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, Australia Sydney Medical School Northern, University of Sydney, NSW, Australia CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia
D. R. Skvarc
Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, PO Box 291, Geelong, Victoria,Australia
Z. X. On
Melbourne School of Psychological Sciences, University of Melbourne, Level 12, Redmond Barry Building 115, Parkville, Victoria, Australia
M. Berk*
Orygen, The National Centre of Excellence in Youth Mental Health, Victoria, Australia Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, PO Box 291, Geelong, Victoria,Australia Department of Psychiatry, University of Melbourne, Level 1 North, Main Block, Royal Melbourne Hospital, Parkville, Victoria,Australia Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, 30 Royal Parade, Parkville, Victoria, Australia
O. M. Dean
Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, PO Box 291, Geelong, Victoria,Australia Department of Psychiatry, University of Melbourne, Level 1 North, Main Block, Royal Melbourne Hospital, Parkville, Victoria,Australia Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, 30 Royal Parade, Parkville, Victoria, Australia
*Address for correspondence: M. Berk, Deakin University, PO Box 281, Geelong, VIC 3220, Australia. (Email:



Cognitive deficits are predictors of functional outcome in patients with psychosis. While conventional antipsychotics are relatively effective on positive symptoms, their impact on negative and cognitive symptoms is limited. Recent studies have established a link between oxidative stress and neurocognitive deficits in psychosis. N-acetylcysteine (NAC), a glutathione precursor with glutamatergic properties, has shown efficacy on negative symptoms and functioning in patients with schizophrenia and bipolar disorder, respectively. However, there are few evidence-based approaches for managing cognitive impairment in psychosis. The present study aims to examine the cognitive effects of adjunctive NAC treatment in a pooled subgroup of participants with psychosis who completed neuropsychological assessment in two trials of both schizophrenia and bipolar disorder.


A sample of 58 participants were randomized in a double fashion to receive 2 g/day of NAC (n = 27) or placebo (n = 31) for 24 weeks. Attention, working memory and executive function domains were assessed. Differences between cognitive performance at baseline and end point were examined using Wilcoxon's test. The Mann–Whitney test was used to examine the differences between the NAC and placebo groups at the end point.


Participants treated with NAC had significantly higher working memory performance at week 24 compared with placebo (U = 98.5, p = 0.027).


NAC may have an impact on cognitive performance in psychosis, as a significant improvement in working memory was observed in the NAC-treated group compared with placebo; however, these preliminary data require replication. Glutamatergic compounds such as NAC may constitute a step towards the development of useful therapies for cognitive impairment in psychosis.

Original Articles
Copyright © Cambridge University Press 2016 

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† Equally contributing authors.


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