N-acetylcysteine for the treatment of comorbid alcohol use disorder and posttraumatic stress disorder: Design and methodology of a randomized clinical trial

Contemp Clin Trials. 2020 Apr:91:105961. doi: 10.1016/j.cct.2020.105961. Epub 2020 Feb 19.

Abstract

Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are two prevalent psychiatric conditions in the U.S. The co-occurrence of AUD and PTSD is also common, and associated with a more severe clinical presentation and worse treatment outcomes across the biopsychosocial spectrum (e.g., social and vocational functioning, physical health) as compared to either disorder alone. Despite the high co-occurrence and negative outcomes, research on effective medications for AUD/PTSD is sparse and there is little empirical evidence to guide treatment decisions. The study described in this paper addresses this knowledge gap by testing the efficacy of N-acetylcysteine (NAC) in reducing alcohol use and PTSD symptoms. Animal studies and prior clinical research suggest a role for NAC in the treatment of substance use disorders and PTSD via glutamate modulation. NAC is a cysteine pro-drug that stimulates the cystine-glutamate exchanger, normalizes glial glutamate transporters, and restores glutamatergic tone on presynaptic receptors in reward regions of the brain. Moreover, NAC is available over-the-counter, has a long-established safety record, and does not require titration to achieve the target dose. This paper describes the rationale, study design, and methodology of a 12-week, randomized, double-blind, placebo-controlled trial of NAC (2400 mg/day) among adults with co-occurring AUD and PTSD. Functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) are utilized to investigate the neural circuitry and neurochemistry underlying comorbid AUD/PTSD and identify predictors of treatment outcome. This study is designed to determine the efficacy of NAC in the treatment of co-occurring AUD/PTSD and provide new information regarding mechanisms of action implicated in co-occurring AUD/PTSD.

Keywords: Alcohol; Alcohol use disorder; N-acetylcysteine; PTSD; Posttraumatic stress disorder.

Publication types

  • Clinical Trial Protocol
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylcysteine* / administration & dosage
  • Acetylcysteine* / adverse effects
  • Acetylcysteine* / therapeutic use
  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Alcoholism* / drug therapy
  • Alcoholism* / epidemiology
  • Alcoholism* / therapy
  • Clinical Trials, Phase II as Topic
  • Cognitive Behavioral Therapy / methods
  • Combined Modality Therapy
  • Double-Blind Method
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Patient Satisfaction
  • Randomized Controlled Trials as Topic
  • Sex Factors
  • Socioeconomic Factors
  • Stress Disorders, Post-Traumatic* / drug therapy
  • Stress Disorders, Post-Traumatic* / epidemiology
  • Stress Disorders, Post-Traumatic* / therapy
  • Veterans
  • Young Adult

Substances

  • Acetylcysteine