Use of Central Nervous System Medications, Opioids Associated with Fall-Related Injury

Data show skeletal muscle relaxant associated with increased risk of fall-related injury (OR 1.28) and all-cause hospitalization (OR 1.11).

The concomitant use of central nervous system (CNS) medications and opioids has increased in older adults ≥65 years, despite associations with an increase in adverse events.

A recent study compared the overall and incremental risk of both fall-related injury (FRI) and all-cause hospitalization linked to sedative hypnotics and skeletal muscle relaxants, in older persistent opioid users.

Investigators, led by Kellyn M. Moran, PharmD, College of Pharmacy, University of Illinois at Chicago, observed an increased risk of FRI and all-cause hospitalization as a result of skeletal muscle relaxant use in the patient population.


The team designed a case-time-control study to evaluate risk of exposure prior to an acute event in comparison to exposure at ≥1 prior time point.

Adult patients aged ≥66 years with persistent opioid use, defined as an episode of opioid dispensing of ≥90 days, were included in the study.

Exclusions included patients with a fracture, long-term care stay, or ≥1 claim for hospice care or care during a 12-month baseline period.

The primary objective was defined as first emergency department (ED) visit, hospitalization, or outpatient visit for a FRI, with a secondary objective included a cohort of cases of first all-cause hospitalization.

The team defined FRI as bone fractures, sprains, strains, dislocations, and superficial skin injuries that occurred on the head, neck, trunk, or upper/lower extremity.

A control for each cohort were risk-set matched by age, sex, and cohort entry

In addition, investigators determined use of opioids, sedative-hypnotics, and skeletal muscle relaxants until index event date through outpatient pharmacy claims.

They also determined exposure to CNS medications prior to the event compared to earlier periods, while the team estimated risk associated with CNS class combinations and sequence of use using logistic regression.


A total of 140,101 older persistent opioid users were included in the study, with 20,723 (14.8%) experiencing fall-related injury and 39,444 hospitalized during the follow-up.

Data show the mean age was 77.4 years, with a majority of female patients (69.7%).

At cohort entry, high-dose persistent opioid use (>90 MME) was observed in 4.2% of older adults.

In addition, the mean days of coverage by the CNS medication of interest in the 181 days prior to index event date included 58.4 days for opioids, 28.7 days for benzodiazepines, 12.4 days for Z-hypnotics, and 8.2 days for skeletal muscle relaxants.

Investigators noted skeletal muscle relaxant was associated with increased risk of fall-related injury, with an odds ratio (OR) of 1.28 for FRI and 1.11 for all-cause hospitalization.

Further, there were statistically significant associations for the joint effects of interactions with skeletal muscle reactions on fall-related injury. They observed OR 1.25 with opioids and OR 1.24 with sedative hypnotic.

For interactions involving opioids on all-cause hospitalization, with OR of 1.10 with sedative hypnotic and OR 1.17 with skeletal muscle relaxant.

Moreover, the addition of a skeletal muscle relaxant to opioid regimen in patients showed a 25% increased risk of fall-related injury, while addition of other CNS medications did not show effects on the risk of all-cause hospitalization.


Investigators observed excess risks of fall-related injury and hospitalization associated with various combinations of CNS medications among older persistent opioid users.

“Evaluating the additional risk associated with various combinations of these medications is important for treatment decision-making, counseling, and monitoring, especially for geriatricians and primary care providers who must often weigh the risks and benefits of using these medications in highly complex clinical care,” investigators wrote.

The study, “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,” was published online in Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy.