Patient and Clinical Factors Associated With Response to Medications for Posttraumatic Stress Disorder

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.

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.

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.

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.