A multi-centre, double-blind, 12-week, randomized, placebo-controlled trial of adjunctive N-Acetylcysteine for treatment-resistant PTSD

Affiliations

¹ University of Melbourne, Department of Psychiatry, Austin Health, Heidelberg, VIC, Australia. Electronic address: richard.kanaan@unimelb.edu.au.
² University of Melbourne, Department of Psychiatry, Austin Health, Heidelberg, VIC, Australia; University of Melbourne, Department of Psychiatry, The Melbourne Clinic, Richmond, VIC, Australia.
³ University of Melbourne, Department of Psychiatry, Austin Health, Heidelberg, VIC, Australia.
⁴ School of Medicine, Barwon Health, Deakin University, IMPACT - The Institute for Mental and Physical Health and Clinical Translation, Geelong, Australia; Deakin University, Faculty of Health, Biostatistics Unit, Geelong, Australia.
⁵ University of Melbourne, Department of Psychiatry, The Melbourne Clinic, Richmond, VIC, Australia.
⁶ Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Ralph H. Johnson VA Medical Center, Charleston, SC, USA.
⁷ Department of Neuroscience, Medical University of South Carolina, USA; Ralph H Johnson VA Medical Center, Charleston, SC, USA.
⁸ School of Medicine, Barwon Health, Deakin University, IMPACT - The Institute for Mental and Physical Health and Clinical Translation, Geelong, Australia; Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, The University of Melbourne, Melbourne, Australia.

PMID: 37540942
DOI: 10.1016/j.psychres.2023.115398

Free article

Randomized Controlled Trial

A multi-centre, double-blind, 12-week, randomized, placebo-controlled trial of adjunctive N-Acetylcysteine for treatment-resistant PTSD

Richard A Kanaan et al. Psychiatry Res. 2023 Sep.

Free article

. 2023 Sep:327:115398.

doi: 10.1016/j.psychres.2023.115398. Epub 2023 Jul 30.

Authors

Affiliations

¹ University of Melbourne, Department of Psychiatry, Austin Health, Heidelberg, VIC, Australia. Electronic address: richard.kanaan@unimelb.edu.au.
² University of Melbourne, Department of Psychiatry, Austin Health, Heidelberg, VIC, Australia; University of Melbourne, Department of Psychiatry, The Melbourne Clinic, Richmond, VIC, Australia.
³ University of Melbourne, Department of Psychiatry, Austin Health, Heidelberg, VIC, Australia.
⁴ School of Medicine, Barwon Health, Deakin University, IMPACT - The Institute for Mental and Physical Health and Clinical Translation, Geelong, Australia; Deakin University, Faculty of Health, Biostatistics Unit, Geelong, Australia.
⁵ University of Melbourne, Department of Psychiatry, The Melbourne Clinic, Richmond, VIC, Australia.
⁶ Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Ralph H. Johnson VA Medical Center, Charleston, SC, USA.
⁷ Department of Neuroscience, Medical University of South Carolina, USA; Ralph H Johnson VA Medical Center, Charleston, SC, USA.
⁸ School of Medicine, Barwon Health, Deakin University, IMPACT - The Institute for Mental and Physical Health and Clinical Translation, Geelong, Australia; Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, The University of Melbourne, Melbourne, Australia.

PMID: 37540942
DOI: 10.1016/j.psychres.2023.115398

Abstract

Background: PTSD may involve oxidative stress, and N-acetylcysteine (NAC) may reduce the impact of oxidative stress in the brain. This study aims to investigate the efficacy of adjuvant NAC in people with treatment-resistant PTSD.

Methods: A multicentre, randomised, double-blind, placebo-controlled trial for adults with PTSD unresponsive to first-line treatment. The intervention was either oral NAC 2.7 g/day or placebo for 12 weeks. The primary outcome was change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at 12 weeks compared with baseline. Secondary outcomes included depression and substance craving. Follow-up measures were obtained at 16 and 64-weeks.

Results: 133 patients were assessed, with 105 randomised; 81 participants completed the 12-week trial, 79 completed week-16 follow-up, and 21 completed week-64 follow-up. There were no significant differences between those taking NAC and those taking placebo in CAPS-5 scores at week 12, nor in secondary outcomes. Significant between-group differences were observed at week 64 in craving duration (Cohen's d = 1.61) and craving resistance (Cohen's d = 1.03), both in favour of NAC.

Conclusion: This was the first multicentre, double-blind, randomised, placebo-controlled trial of adjunctive NAC for treatment-resistant PTSD. No benefit of NAC was observed in this group beyond that provided by placebo at end of the trial.

Trial registration: ACTRN12618001784202, retrospectively registered 31/10/2018, URL: http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376004.

Keywords: N-acetyl cysteine; Oxidative stress; Post-traumatic stress disorder; Randomised controlled trial; Treatment.

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Conflict of interest statement

Declaration of Competing Interest MB has received grant support from MRFF, NHMRC Senior Principal Research Fellowship 1156072, Congressionally Directed Medical Research Programs (CDMRP) USA, AEDRTC Australian Eating Disorders Research and Translation Centre, Patient-Centered Outcomes Research Institute (PCORI), Baszucki Brain Research Fund, Danmarks Frie Forskningsfond. Psykiatrisk Center Kobenhavn, Stanley Medical Research Institute, Victorian Government Department of Jobs, Precincts and Regions, Wellcome Trust, Victorian Medical Research Acceleration Fund, Centre for Research Excellence CRE, Victorian COVID-19 Research Fund. He has had consultancies with Lundbeck, Controversias Barcelona, Servier, Medisquire, HealthEd, ANZJP, EPA, Janssen, Medplan, RANZCP, Abbott India, ASCP, Headspace, Sandoz, Aust Psychosis, International Society of Bipolar Disorder, Precision Psychiatry, Penn State College of Medicine, Shanghai Mental Health Centre. (Last 3 years) – all unrelated to this work. CHN served as a consultant for Janssen-Cilag, Lundbeck, Grunbiotics, Servier and Eli Lilly, and speaker honoraria from Servier, Lundbeck, Eli Lilly, Janssen-Cilag, Astra-Zeneca, and Pfizer in the last 5 years – all unrelated to this study. The other authors declare they have no competing interests

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A multi-centre, double-blind, 12-week, randomized, placebo-controlled trial of adjunctive N-Acetylcysteine for treatment-resistant PTSD

Affiliations

A multi-centre, double-blind, 12-week, randomized, placebo-controlled trial of adjunctive N-Acetylcysteine for treatment-resistant PTSD

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

Substances

Associated data

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous