Risk of Opioid Overdose Associated With Concomitant Use of Opioids and Skeletal Muscle Relaxants: A Population‐Based Cohort Study

The recent opioid prescribing guideline cautions about the concomitant prescribing of opioids and skeletal muscle relaxants (SMRs) given the additive central nervous system depressant effect. However, the clinical relevance remains unclear. In this retrospective cohort study, we compared the risk of opioid overdose associated with concomitant use of opioids and SMRs vs. opioid use alone. Adjusted hazard ratios were 1.09 (95% confidence interval (CI), 0.74–1.62) and 1.26 (95% CI, 1.00–1.58) in the incident and prevalent opioid user cohorts, respectively, generating a combined estimate of 1.21 (95% CI, 1.00–1.48). This risk seemed to increase with treatment duration (≤ 14 days: 0.91 and 95% CI, 0.67–1.22; 15–60 days: 1.37 and 95% CI, 0.81–2.37; >60 days: 1.80 and 95% CI, 1.30–2.48) and for baclofen (1.83 and 95% CI, 1.11–3.04) and carisoprodol (1.84 and 95% CI, 1.34–2.54). Concomitant users with daily opioid dose ≥50 mg (1.50 and 95% CI, 1.18–1.92) and benzodiazepine use (1.39 and 95% CI, 1.08–1.79) also had elevated risk. Clinicians should be cautious about these potentially unsafe practices to optimize pain care and improve patient safety.