• Jonathan Hirohiko Watanabe and Jincheng Yang.
• Division of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive MC 0657, La Jolla, CA, 92093-0657, USA. jhwatanabe@ucsd.edu.
• Int J Clin Pharm. 2021 Apr 1; 43 (2): 358-364.

AbstractBackground Concurrent opioid and benzodiazepine use ("double-threat") and opioid, benzodiazepine, and muscle relaxant use ("triple-threat") are linked to increased adverse events compared to opioid use alone. Objectives To assess prevalence of double-threat and triple-threat in the US and to measure association between double- and triple-threat and emergency department visits. Setting Nationally representative, 2-year health database of the United States. Method A retrospective cohort study was conducted using the national medical expenditure panel survey. Two-year prevalence of combination use was measured. Association between 2013-2014 double- and triple-threat exposure and emergency department visit compared to non-users, opioid-users, and all other exposure combinations assessed using logistic regression. Main outcome measures Survey-weighted prevalence of triple-threat and double-threat in 2013 and 2014 was measured. The outcome variable of at least one emergency department visit in a study year was utilized for the logistic regression. Results Opioids, benzodiazepines, and muscle relaxants were used in 11.9% (38.4 million lives), 4.2% (13.5 million), and 3.4% (10.9 million) individuals respectively in 2013, and 12.2% (39.3 million), 4.6% (14.8 million), and 3.6% (11.6 million), respectively in 2014. Prevalence of individuals on double-threat rose from 1.6 to 1.9% from 2013 to 2014. Triple-threat prevalence was unchanged at 0.53% in that interval. Triple-threat patients had increased emergency department visit probability with ORs of 9.19 (95% CI 9.17-9.22) in 2013, 9.82 (95% CI 9.79-9.85) in 2014, and 5.90 (95% CI 5.89-5.92) for longitudinal 2013-2014 analysis compared to non-users. Double-threat patients had increased emergency department visit probability with ORs of 4.57 (95% CI 4.56-4.58) in 2013, 6.66 (95% CI 6.65-6.68) in 2014, and 4.49 (95% CI 4.48-4.50) for 2013-2014 analysis compared to non-users. Conclusions Concurrent opioid and benzodiazepine use and opioid, benzodiazepine, and muscle relaxant use increased probability of emergency department visit. Amplified efforts in surveillance, prescribing, and default follow-up for concurrent opioid, benzodiazepine, muscle relaxant use are needed to reduce this public health concern.

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