title: A Double-Blind, Randomized, Controlled Pilot Trial of N-Acetylcysteine in Veterans With Posttraumatic Stress Disorder and Substance Use Disorders.
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.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT02499029.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 5 Charleston Center Dr, Ste 151, Charleston, SC 29407. backs@musc.edu.|Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.|Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, USA.
authors.forename: Sudie E
authors.initials: SE
authors.lastname: Back
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Jenna L
authors.initials: JL
authors.lastname: McCauley
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.|Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, USA.
authors.forename: Kristina J
authors.initials: KJ
authors.lastname: Korte
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.|Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, USA.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gros
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Leavitt
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Gray
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.|Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, USA.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Hamner
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Stacia M
authors.initials: SM
authors.lastname: DeSantis
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.|Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Malcolm
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.|Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, USA.
authors.forename: Kathleen T
authors.initials: KT
authors.lastname: Brady
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Kalivas
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D000437:Alcoholism / Q000175:diagnosis / Q000523:psychology / Q000534:rehabilitation*; D015928:Cognitive Behavioral Therapy; D003130:Combat Disorders / Q000175:diagnosis / Q000523:psychology / Q000534:rehabilitation*; D003131:Combined Modality Therapy; D015897:Comorbidity; D066249:Craving / Q000187:drug effects; D017831:Diagnosis, Dual (Psychiatry); D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013313:Stress Disorders, Post-Traumatic / Q000175:diagnosis / Q000523:psychology / Q000534:rehabilitation*; D019966:Substance-Related Disorders / Q000175:diagnosis / Q000523:psychology / Q000534:rehabilitation*; D014728:Veterans / Q000523:psychology*
chemical_list: D000111:Acetylcysteine