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Original Research

A Double-Blind, Randomized, Controlled Pilot Trial of N-Acetylcysteine in Veterans With Posttraumatic Stress Disorder and Substance Use Disorders

Sudie E. Back, PhD; Jenna L. McCauley, PhD; Kristina J. Korte, MS; Daniel F. Gros, PhD; Virginia Leavitt, MEd; Kevin M. Gray, MD; Mark B. Hamner, MD; Stacia M. DeSantis, PhD; Robert Malcolm, MD; Kathleen T. Brady, MD, PhD; and Peter W. Kalivas, PhD

Published: November 23, 2016

Article Abstract

Objective: The antioxidant N-acetylcysteine is being increasingly investigated as a therapeutic agent in the treatment of substance use disorders (SUDs). This study explored the efficacy of N-acetylcysteine in the treatment of posttraumatic stress disorder (PTSD), which frequently co-occurs with SUD and shares impaired prefrontal cortex regulation of basal ganglia circuitry, in particular at glutamate synapses in the nucleus accumbens.

Methods: Veterans with PTSD and SUD per DSM-IV criteria (N = 35) were randomly assigned to receive a double-blind, 8-week course of N-acetylcysteine (2,400 mg/d) or placebo plus cognitive-behavioral therapy for SUD (between March 2013 and April 2014). Primary outcome measures included PTSD symptoms (Clinician-Administered PTSD Scale, PTSD Checklist-Military) and craving (Visual Analog Scale). Substance use and depression were also assessed.

Results: Participants treated with N-acetylcysteine compared to placebo evidenced significant improvements in PTSD symptoms, craving, and depression (β values < -0.33; P values < .05). Substance use was low for both groups, and no significant between-group differences were observed. N-acetylcysteine was well tolerated, and retention was high.

Conclusions: This is the first randomized controlled trial to investigate N-acetylcysteine as a pharmacologic treatment for PTSD and SUD. Although preliminary, the findings provide initial support for the use of N-acetylcysteine in combination with psychotherapy among individuals with co-occurring PTSD and SUD.

Trial Registration: ClinicalTrials.gov identifier: NCT02499029

Volume: 77

Quick Links: PTSD , Trauma

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