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Association of combination opioid, benzodiazepine, and muscle relaxant usage with emergency department visits in a nationwide cohort in the United States

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Abstract

Background 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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Acknowledgements

Dr. Watanabe receives support from the Health Resources and Services Administration (HRSA) of the US. Department of Health and Human Services (HHS) under Grant U1WQHP28726, “Geriatrics Workforce Enhancement Program.” Dr. Watanabe receives research support from the State of California Tobacco-Related Disease Research Program Award No. 588100 and from the National Academy of Medicine Anniversary Pharmacy Fellowship Program. He also receives support from the National Academy of Medicine Emerging Leaders in Health and Medicine Scholars program. This information, content, and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS, or the US. government, the state of California, or the National Academies of Sciences, Engineering, and Medicine.

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  1. 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

    Jonathan Hirohiko Watanabe & Jincheng Yang

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  1. Jonathan Hirohiko Watanabe
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Correspondence to Jonathan Hirohiko Watanabe.

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Watanabe, J.H., Yang, J. Association of combination opioid, benzodiazepine, and muscle relaxant usage with emergency department visits in a nationwide cohort in the United States. Int J Clin Pharm 43, 358–364 (2021). https://doi.org/10.1007/s11096-020-01012-5

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