Hospitalization and Combined Use of Opioids, Benzodiazepines, and Muscle Relaxants in the United States.

Concurrent opioid and benzodiazepine use ("double-threat") and double-threat and muscle relaxant use ("triple-threat") are postulated to increase morbidity versus opioids alone. Study objectives were to measure association between double- and triple-threat exposure and hospitalizations in a validated, nationally representative database of the United States. A retrospective cohort study was conducted using the 2013 and 2014 Medical Expenditure Panel Survey (MEPS) longitudinal dataset and affiliated Prescribed Medicines Files. Association between 2013 and 2014 double- and triple-threat exposures and outcome of hospitalizations compared to nonusers, opioid users, and all combinations were assessed via logistic regression. The cohort surveyed in MEPS has been weighted to be reflective of the actual US population in the years 2013 and 2014. Logistic regression applying the subject-level MEPS survey weights was performed to measure association via odds ratios (ORs) of medication exposures with the outcome of all-cause hospitalization. Study subjects were categorized into exposure groups as nonusers (nonuse of opioids, benzodiazepines, or muscle relaxants), opioid users, benzodiazepine users, muscle relaxant users, "double-threat" users, and "triple-threat" users. Analyses were conducted using RStudio 1.1.5 (Boston, MA) with α level = 0.05 for all comparisons. Opioids, benzodiazepines, and muscle relaxants were used in 11.9% (38.4 million), 4.2% (13.5 million), and 3.4% (10.9 million) lives of the United States in 2013, respectively. Double-threat prevalence rose from 1.6% to 1.9% from 2013 to 2014. Triple-threat prevalence remained unchanged at 0.53%. Compared to nonusers, triple-threat patients increased hospitalization probability with ORs of 8.52 (95% confidence interval [CI]: 8.50-8.55) in 2013, 5.06 (95% CI: 5.04-5.08) in 2014, and 4.61 (95% CI: 4.59-4.63) in the 2013-2014 longitudinal analysis. Compared to nonusers, double-threat patients increased hospitalization probability with ORs of 5.71 (95% CI: 5.69-5.72) in 2013, 11.47 (95% CI: 11.44-11.49) in 2014, and 5.59 (95% CI: 5.57-5.60) in the longitudinal analysis. Concurrent opioid and benzodiazepine use and opioid, benzodiazepine, and muscle relaxant use were associated with increased hospitalization likelihood. Amplified efforts in surveillance, prescribing, monitoring, and deprescribing for concurrent opioid, benzodiazepine, and muscle relaxant use are needed to reduce this public health concern.