Review of: Back SE et al. A double-blind, randomized, controlled pilot trial of N-acetylcysteine in veterans with post traumatic stress disorder and substance use disorder. J Clin Psychiatry, dx.doi.org/10.4088/JCP.15m10239.

Study type: Double-blind, ­randomized, controlled trial

Post-traumatic stress disorder (PTSD) is the most common psychiatric disorder in veterans who seek treatment at the VA, and substance use disorder (SUD) is a common comorbid condition. While SSRIs can be effective for PTSD symptoms, they don’t treat SUD well.

N-acetylcysteine (NAC) is an antioxidant approved for the treatment of acetaminophen overdose and pulmonary disease, and it has been used in psychiatry for patients with trichotillomania and gambling, among other conditions. Neurochemically, NAC normalizes synaptic glutamate transmission, and ­hypothetically such transmission is disordered in both PTSD and SUD. Therefore, researchers decided to try the medication in a group of veterans with PTSD and SUD.

Thirty-five veterans aged 18–65 from the Ralph H. Johnson VA Medical Center were enrolled; they all met DSM-IV criteria for SUD and PTSD. After at least one week of sobriety, they were randomly assigned to double-blind treatment with either NAC or placebo. The active treatment group received 2,400 mg of NAC daily for 8 weeks. Both groups attended a cognitive behavioral therapy–based outpatient program that met 5 days per week during the study. All patients were assessed with standard research scales for PTSD symptoms, such as the Clinician-Administered PTSD scale (CAPS), and the PTSD Checklist Military (PCL-M); they were also assessed for depression and substance craving. The study was funded by several government agencies, including the Department of Veterans Affairs and the National Institute for Drug Addiction.

Results
Over the course of 8 weeks, patients in the NAC group (N = 13 after dropouts) improved significantly on all measures (p < 0.05), whereas those assigned to placebo (N = 14) improved on only one measure: the CAPS re-experiencing subscale. By week 8, the NAC group had reductions of 46% in the CAPS and 32% on the PCL-M, while the placebo group had reductions of 25% and 3% respectively. There was an 81% reduction in craving in the NAC group compared to 32% in the placebo group. Adverse effects were mild, with the most common being dry mouth and heartburn.

TCPR’s Take
The pilot study has some limitations: Its sample size was small, and it lacked any measure of whether quality of life was improved by symptom reduction. Nonetheless, the symptom improvement for both PTSD and substance craving in the NAC group were impressive.

Practice implications
Given the lack of effective treatments for co-occurring PTSD and SUD, it’s reasonable to try NAC at 2,400 mg/day for such patients. The side effects are minimal, and the improvements in symptoms may be significant.