Polypharmacy, Outpatient Prescriptions and TBI Risk: a systematic review

In recent decades, there has been a shift in TBI epidemiology, with a rising incidence in older adults. Medication use is an often-overlooked modifiable TBI risk factor. There is a paucity of research specifically examining the relationship between individual medications, polypharmacy, and the risk of TBI. With the goal of informing TBI prevention strategies as well as future research, we conducted a systematic review to assess the association between specific medication use, polypharmacy, and the risk of TBI.

This systematic review follows the PRISMA guidelines and was prospectively registered in PROSPERO. We conducted a literature search of the following databases: MEDLINE, EMBASE, PsycINFO, Global Health, CINAHL, and Web of Science. We included all randomized controlled, quasi-experimental or observational studies reporting on polypharmacy or single medications and the risk of TBI. We excluded pediatric studies, trauma studies that did not report specifically on TBI, animal studies, case series, and case reports. Reviewers independently evaluated studies according to inclusion and exclusion criteria and risk of bias.

After duplicate removal, our research strategy identified 18,528 studies, of which 197 abstracts were selected for full-text review. Sixteen studies met our inclusion criteria. In total, 7 medication classes and 27 single medications were studied. A single study reported on polypharmacy. Four studies on antithrombotics reported an association with an increased risk of TBI. In 2 studies, antidepressants were associated with an increased risk of TBI. Two studies on antipsychotics showed an association with an increased risk of TBI. One study found a significant increase in the risk of TBI with the use of benzodiazepines. Results on z-drugs were inconsistent, with one study reporting a significant increase in TBI risk with zolpidem but not eszopiclone. The single study evaluating opioids reported an increased risk of TBI. Finally, antiarrhythmics were associated with an increased risk of TBI.

In robust studies, antipsychotics, antidepressants, hypnotics, and opioids have all been associated with an increased risk of TBI, while studies on antithrombotics are inconsistent. Further studies are needed to evaluate the risk of these drugs in the general population, especially in the elderly.