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.

Trial registration: ClinicalTrials.gov identifier: NCT02499029.

Figure 1

Enrollment and Study Flow of Veterans with PTSD and SUD assigned to N-Acetylcysteine or placebo

Figure 2. Change in PTSD Symptoms and Drug Craving Over Time by Treatment Condition

A) Weekly total score on the PTSD Military Checklist (PCL-M). NAC (N-acetylcysteine) showed a significant treatment effect to reduce PTSD symptoms over the 8-week treatment period. Follow-up measure was obtained 4 weeks after discontinuing NAC or placebo (i.e., week 12 of the study) B) Weekly subjective craving score measured using a Visual Analog Scale (VAS). NAC showed a significant treatment effect to reduce drug craving over the 8-week treatment period. *p<.05. B = Baseline, F = Follow-Up.