Objective: Fluoxetine, paroxetine, sertraline, topiramate, and venlafaxine have previously shown efficacy for posttraumatic stress disorder (PTSD) in randomized clinical trials. Two prior studies using Department of Veterans Affairs (VA) medical records data show these medications are also effective in routine practice. Using an expanded retrospective cohort, we assessed the possibility of differential patterns of response based on patient and clinical factors. Methods: We identified 6,839 VA outpatients with clinical diagnoses of PTSD between October 1999 and September 2019 who initiated one of the medications and met pre-specified criteria for treatment duration and dose, combined with baseline and endpoint PTSD checklist (PCL) measurements. We compared 12-week changes in PCL score within clinical subgroups defined by sex, race and ethnicity, and military exposures, as well as comorbidities. Comorbidities were identified using International Classification of Diseases diagnostic codes and grouped according to major diagnostic classifications in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (eg, Psychotic Disorders, Depressive Disorders). We used a propensity score weighting approach to balance covariates among medication arms within each clinical subgroup. In our exploratory analyses using unweighted data for the overall cohort, we built penalized logistic regression models to identify covariates that predicted meaningful improvement. Results: There were no significant differences between medications in our weighted subgroup analyses. In unweighted exploratory analyses, higher baseline PCL scores and concurrent receipt of evidence-based psychotherapy predicted meaningful improvement, while high levels of disability predicted not realizing meaningful improvement. Conclusions: In the largest real-world study of medications for PTSD to date, we did not observe a pattern of differential response among clinical subgroups. All patients taking medications for PTSD, especially those with the highest levels of disability, should consider combined treatment with evidence-based psychotherapy.

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We recently conducted an exploratory study that indicated that several direct-acting antivirals (DAAs), highly effective medications for hepatitis C virus (HCV) infection, were also associated with improvement in posttraumatic stress disorder (PTSD) among a national cohort of US Department of Veterans Affairs (VA) patients treated between October 1, 1999, and September 30, 2019. Limiting the same cohort to patients with PTSD and HCV, we compared the associations of individual DAAs with PTSD symptom improvement using propensity score weighting. After identifying patients who had available baseline and endpoint PTSD symptom data as measured with the PTSD Checklist (PCL), we compared changes over the 8–12 weeks of DAA treatment. The DAAs most prescribed in conjunction with PCL measurement were glecaprevir/pibrentasvir (GLE/PIB; n = 54), sofosbuvir/velpatasvir (SOF/VEL; n = 54), and ledipasvir/sofosbuvir (LDV/SOF; n = 145). GLE/PIB was superior to LDV/SOF, with a mean difference in improvement of 7.3 points on the PCL (95% confidence interval (CI): 1.1, 13.6). The mean differences in improvement on the PCL were smaller between GLE/PIB and SOF/VEL (3.0, 95% CI: −6.3, 12.2) and between SOF/VEL and LDV/SOF (4.4, 95% CI: −2.4, 11.2). While almost all patients were cured of HCV (92.5%) regardless of the agent received, PTSD outcomes were superior for those receiving GLE/PIB compared with those receiving LDV/SOF, indicating that GLE/PIB may merit further investigation as a potential PTSD treatment.

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