Revealing Unknown Benefits of Existing Medications to Aid the Discovery of New Treatments for Post‐Traumatic Stress Disorder

Objective To systematically identify novel pharmacological strategies for preventing or treating post‐traumatic stress disorder (PTSD) by leveraging large‐scale analysis of real‐world observational data. Methods Using a self‐controlled study design, the association between 1399 medications and the incidence of PTSD across four US insurance claims databases covering commercially insured, Medicare eligible, and Medicaid patients was examined. A validated algorithm for identifying PTSD in claims data was used, and medications were identified by their RxNorm ingredient. Medications used to treat PTSD or its symptoms (e.g., antidepressants, antipsychotics) were excluded. Medications associated with ≥30% reduction in risk of PTSD in ≥2 databases were identified. Results A total of 137,182,179 individuals were included in the analysis. Fifteen medications met the threshold criteria for a potential protective effect on PTSD; six were categorized as “primary signals” while the remaining nine were considered “potential signals”. The primary signals include a beta blocker that has been previously studied for PTSD, and five medications used to treat attention‐deficit/hyperactivity disorder. The potential signals include four medications used to treat substance use disorders and five medications used to treat sleep disorders. Discussion The medications identified in this analysis provide targets for further research in studies that are designed to examine specific hypotheses regarding these medications and the incidence of PTSD. This work may aid in discovering novel therapeutic approaches to treat PTSD, wherein new and effective treatments are badly needed. Highlights Four large US‐based administrative claims databases were used to analyze the association between all marketed prescription medications and the outcome of incident post‐traumatic stress disorder (PTSD) Of the 1399 medications examined, there were 15 that met the strict filtering criteria for showing consistent, moderate‐to‐strong, protective effects against the outcome Medications fell into four main classes: (1) a beta blocker (propranolol), (2) five medications used to treat attention‐deficit/hyperactivity disorder (ADHD), (3) four medications used to treat substance use disorders and (4) five medications used to treat sleep disorders These findings identify rational starting points for future hypothesis‐driven research to explore these associations in greater detail