Prevalence, Predictors, and Risks of Central Nervous System Drug Combinations in Older Adult Opioid Users

Use of central nervous system (CNS) medication combinations may be common in older adults with a history of persistent opioid use due to comorbidities and multimodal approaches to pain management. There is limited longitudinal data about the prevalence and trends of CNS polypharmacy in this population, and there are gaps in evidence regarding its impact on the risk of fall-related injury. Fall-related injuries can have significant clinical and economic consequences; therefore, weighing the risks and benefits is important for safe medication management. The goal of this dissertation was to describe real-world trends and assess the safety of CNS polypharmacy within this population. Three studies were conducted to meet this goal. The aim of the first study was to describe trends in CNS polypharmacy among older adults with a history of persistent opioid use. The second study identified and characterized individual trajectories of the number of concomitant CNS medications and assessed the risk of fall-related injury associated with these trajectories. The third study compared the overall and incremental risk of fall-related injury associated with specific combinations and sequence of use of CNS medication classes. Overall, the evidence generated in this dissertation suggests that CNS polypharmacy is prevalent among older adults with a history of persistent opioid use. Most individuals have stable use patterns of CNS medications overtime, but these patterns were associated with differential risks of fall-related injury. Notably, patients using a decreasing number of CNS medications reduced their risk for fall-related injury. Finally, the sequence of CNS medication use may be important when modifying a medication regimen; however, it is also critical to consider the influence of specific medications such as skeletal muscle relaxants. Future studies could expand to other populations, including those with acute opioid use, identify drivers of CNS polypharmacy, and evaluate the appropriateness of different CNS medication combinations in addition to the safety risks.