Risk of fall-related injury and all-cause hospitalization of select concomitant central nervous system medication prescribing in older adult persistent opioid users: A case-time-control analysis.

Background Concomitant use of central nervous system (CNS) medications frequently occurs in older adults with persistent opioid use. The risks of adverse outcomes associated with combinations of opioids, sedative-hypnotics, or skeletal muscle relaxants have not been sufficiently described in this population. Objective To compare the overall and incremental risk of 1) fall-related injury and 2) all-cause hospitalization associated with sedative hypnotics and skeletal muscle relaxants among older persistent opioid users. Methods A case-time-control study was conducted using administrative claims of adults ages ≥66 years with a history of persistent (≥90 days) opioid use. Cases included those with first 1) emergency department, hospital, or outpatient visit for a fall-related injury, or 2) all-cause hospitalization. Exposure to CNS medications prior to the case event versus earlier periods, and the risk associated with CNS drug class combinations and sequence of use, was estimated using conditional logistic regression, adjusted for time trends and time-varying covariates. Results Among 140,101 older persistent opioid users, 20,723 experienced fall-related injury and 39,444 were hospitalized during follow-up. Skeletal muscle relaxant use was associated with an increased risk of fall-related injury (Odds ratio [OR] 1.28) and all-cause hospitalization (OR 1.11). Statistically significant associations were observed for the joint effects of interactions involving skeletal muscle relaxants on fall-related injury (with opioid: OR 1.25; with sedative hypnotic: OR 1.24), and interactions involving opioids on all-cause hospitalization (with sedative hypnotic: OR 1.10; with skeletal muscle relaxant: OR 1.17). The addition of a skeletal muscle relaxant to an opioid regimen was associated with a 25% increased risk of fall-related injury. Additions of other CNS medications did not have apparent incremental effects on the risk of all-cause hospitalization. Conclusion The excess risks of fall-related injury and hospitalization associated with various combinations of CNS medications among older persistent opioid users should be considered in therapeutic decision-making. Further research is needed to confirm these findings.