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

J Clin Psychiatry. 2016 Nov;77(11):e1439-e1446. doi: 10.4088/JCP.15m10239.

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Adult
  • Alcoholism / diagnosis
  • Alcoholism / psychology
  • Alcoholism / rehabilitation*
  • Cognitive Behavioral Therapy
  • Combat Disorders / diagnosis
  • Combat Disorders / psychology
  • Combat Disorders / rehabilitation*
  • Combined Modality Therapy
  • Comorbidity
  • Craving / drug effects
  • Diagnosis, Dual (Psychiatry)
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Stress Disorders, Post-Traumatic / diagnosis
  • Stress Disorders, Post-Traumatic / psychology
  • Stress Disorders, Post-Traumatic / rehabilitation*
  • Substance-Related Disorders / diagnosis
  • Substance-Related Disorders / psychology
  • Substance-Related Disorders / rehabilitation*
  • Veterans / psychology*

Substances

  • Acetylcysteine

Associated data

  • ClinicalTrials.gov/NCT02499029