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A multi-centre, double-blind, 12-week, randomized, placebo-controlled trial to assess the efficacy of adjunctive N-Acetylcysteine for treatment-resistant PTSD: A study protocol

Maier, A, Dharan, A, Oliver, G, Berk, Michael, Redston, S, Back, SE, Kalivas, P, Ng, C and Kanaan, RA 2020, A multi-centre, double-blind, 12-week, randomized, placebo-controlled trial to assess the efficacy of adjunctive N-Acetylcysteine for treatment-resistant PTSD: A study protocol, BMC Psychiatry, vol. 20, no. 1, pp. 1-9, doi: 10.1186/s12888-020-02793-9.

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Title A multi-centre, double-blind, 12-week, randomized, placebo-controlled trial to assess the efficacy of adjunctive N-Acetylcysteine for treatment-resistant PTSD: A study protocol
Author(s) Maier, A
Dharan, A
Oliver, G
Berk, MichaelORCID iD for Berk, Michael orcid.org/0000-0002-5554-6946
Redston, S
Back, SE
Kalivas, P
Ng, C
Kanaan, RA
Journal name BMC Psychiatry
Volume number 20
Issue number 1
Article ID 397
Start page 1
End page 9
Total pages 9
Publisher BMC
Place of publication London, Eng.
Publication date 2020-08-06
ISSN 1471-244X
Keyword(s) Clinical trial protocol
Post-traumatic stress disorder
N-acetyl cysteine
Adjunctive therapy
Randomised clinical trial
Oxidative stress
Biomarker
Science & Technology
Life Sciences & Biomedicine
Psychiatry
POSTTRAUMATIC-STRESS-DISORDER
ACETYL CYSTEINE
DEPRESSIVE SYMPTOMS
SCHIZOPHRENIA
PSYCHOTHERAPY
METAANALYSIS
IMPAIRMENT
BIOMARKERS
SEVERITY
VETERANS
Summary Background: Most patients with Posttraumatic Stress Disorder (PTSD) suffer residual symptoms following first-line treatment. Oxidative stress has been implicated in the pathophysiology of PTSD. N-acetylcysteine (NAC) is a precursor of the brain's primary antioxidant, glutathione, and may diminish oxidative cellular damage. An 8-week pilot study of NAC in veterans with PTSD found that symptoms were significantly reduced in the NAC group compared to placebo. This study aims to confirm these findings with a larger sample in a double-blind, placebo-controlled trial to further explore the efficacy of NAC as an adjunctive therapy in treatment-resistant PTSD. Methods: A multicentre, randomised, double-blind, placebo-controlled trial for adult patients who still meet criteria for PTSD following first-line treatment. The intervention comprises either NAC as a fixed dose regime of 2.7 g/day (900 mg three times daily) administered orally for 12 weeks, or placebo. Standard care for PTSD will continue in addition, including other pharmacotherapies. Detailed clinical data will be collected at randomisation and weeks 4, 8, 12, 16, and 64 post-randomisation, with self-report measures completed weekly from baseline to 16 weeks and at 64 weeks post-randomisation. Blood-based biomarkers will be collected at baseline and 12 weeks to assess the mechanism of effect. The primary outcome measure will be change in Clinician-Administered PTSD Scale for DSM-5 at 12 weeks compared with baseline. Secondary outcomes will be change in quality of life, depression, anxiety, substance use and craving, and somatic symptoms. With 126 completed participants (63 per arm), the study is powered at 80% to detect a true difference in the primary outcome measure using a two-tailed analysis with alpha = 0.05, beta = 0.2. Discussion: This is the first multicentre, double blind, randomised, placebo-controlled trial of adjunctive NAC for treatment-resistant PTSD. NAC has an established safety profile, is readily available and easy to administer, and has a favourable tolerability profile, therefore making it an attractive adjunctive therapy. Inclusion of blood analyses to assess potential target engagement biomarkers of oxidative stress and neuroinflammation may help gauge the biological mechanisms of effect of NAC. Trial registration: ACTRN12618001784202, retrospectively registered 31/10/2018, URL: http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376004.
Language eng
DOI 10.1186/s12888-020-02793-9
Indigenous content off
Field of Research 110999 Neurosciences not elsewhere classified
1103 Clinical Sciences
1117 Public Health and Health Services
1701 Psychology
Socio Economic Objective 920410 Mental Health
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2020, The Author(s)
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30140760

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.