Comparative Effectiveness of Long Acting Injectable Versus Oral Naltrexone in Patients with Co-Occurring...

To compare the effectiveness of long-acting injectable (LAI) versus oral naltrexone in improving post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) outcomes in United States Department of Veterans Affairs (VA) patients with co-occurring PTSD and AUD.

We reviewed medical records of patients with PTSD and AUD receiving VA care from 10/1/1999 and 9/30/2019. Participants met eligibility criteria for an emulated clinical trial comparing LAI and oral naltrexone (n = 3739). We used inverse probability weights to adjust for possible confounding. PTSD symptom change was assessed using the PTSD Checklist for DSM-V (PCL-5). Alcohol consumption and adverse psychiatric outcomes were also assessed in a 2-year continuity phase.

Under the assumption of no residual confounding, we estimated that continuous use of LAI was associated with a 11.9% decrease 95% CI [-22.3, 0.8] in the probability of having clinically meaningful improvement in PTSD symptoms compared to continuous oral naltrexone use over 12-weeks. However, we found no difference in improvement comparing initiation of LAI versus oral naltrexone (-1.8% [95% CI: -11.4, 7.4]). No differences were observed in the probability of PTSD remission, probability of AUD remission, or rates of adverse psychiatric outcomes.

Our analyses suggest that LAI naltrexone provides no benefits in improving PTSD or AUD outcomes compared to its oral counterpart among patients with comorbid PTSD and AUD. In fact, our results suggest that oral naltrexone may provide an increased probability of clinically meaning PTSD improvements if a high level of medication adherence is maintained.