N-acetylcysteine as an adjunctive treatment in treatment-resistant posttraumatic stress disorder: A randomised controlled trial

Abstract

Background: Posttraumatic stress disorder (PTSD) is hard to treat effectively, as most patients who receive the standard treatments still have PTSD symptoms afterwards. Evidence exists that indicates that a drug called n-acetylcysteine (NAC), which supports the body’s anti-oxidants, can help to treat PTSD, as well as comorbid depression and addictions.

Aim: This study aims to investigate the efficacy of NAC as an adjunct to first line treatment in treatment-resistant PTSD. The primary outcome measures will be the core PTSD symptoms, as measured by the Clinician Administered PTSD Scale (CAPS-5). Secondary outcomes include depressive and somatic symptoms, substance use, functioning, and quality of life. Biomarkers of PTSD will also be measured to explore the potential mechanisms of the effect of NAC on PTSD symptoms.

Study Design: A 12-week, double blind, randomised, placebo-controlled trial of NAC, given as an adjunct to those who still have PTSD despite having received first line treatment. This study will be conducted at the Psychological Trauma Recovery Service at the Heidelberg Repatriation Hospital, Melbourne, a specialist PTSD treatment centre. The study will also be conducted at the Melbourne Clinic, a private psychiatric hospital that provides specialised PTSD services. We will recruit 126 participants (63 per arm). All will be over 18; have the capacity to consent; fulfil the criteria for current PTSD and have undergone a full course of treatment for their PTSD. They will remain on their standard treatment during the study. The trial clinician will contact all those referred and screen for suitability through a face-to-face interview, confirming the diagnosis using the CAPS-5, and obtaining written informed consent. Individuals accepted into the trial will be randomly allocated in a double-blind fashion to receive either NAC or placebo, in addition to any established treatments for their PTSD. A fixed dose regime of 2.7g/day of NAC/placebo will be used. Clinical measures will be completed at baseline, weeks 4, 8 and 12 of the trial, and 4 weeks after trial discontinuation. These measures include the CAPS-5 (a PTSD scale), the HADS (a depression and anxiety scale), the HAM-D (a depression scale), the WHO-QOL BREV (a quality of life scale), the AUDIT (an alcohol and drug use scale), a likert scale of their substance craving, and the PHQ-15 (a measure of somatic symptoms). Participants will also be asked to complete one questionnaire, the PCL-5, each week on their own. The first assessment will take about 90 minutes; the 4-weekly questionnaires take about 40 mins to 1 hour to complete; the weekly self-report questionnaire will take no more than 5 minutes. Participants will be provided the option to undertake blood analysis at baseline and at week 12 of the trial (to assess biomarkers of PTSD).

Trial information: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376004&isReview=true

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