A Systematic Review of Concomitant Opioid and Sedative or Skeletal Muscle Relaxant Use on Patient Outcomes in Chronic NON-Malignant PAIN

Purpose: Multiple studies show risks with concomitant opioid and benzodiazepine use in the general population, but few discusses effect of opioids with other sedatives, when policies are not in consensus. This review is a comprehensive outlook of current evidence analyzing the impact of concomitant opioid and sedative use in chronic non-malignant pain. METHODS: Literature search strategy using phrase "opioid AND CNS depressants OR benzodiazepine OR sedatives OR gabapentinoids NOT cancer" was conducted in PubMed, Embase, Web of Science, and Scopus. Excluded case reports, reviews, pediatric, duplicates, and non-opioid-related outcome studies(N=43,914) for total 14 articles. RESULTS: 12 studies were retrospective. Overall, concomitant use of sedatives or muscle relaxants with opioids was associated with hospitalizations(N=5), mortality(N=4), motor vehicle accidents(N=1), inappropriate drug utilization(N=4), or anxiety and depression(N=2). Higher dosages of opioids(N=4) corresponded to negative outcomes regardless of concomitant medications. South and increasing age had higher prevalence of concomitant use but was not always associated with negative outcomes. CONCLUSIONS: Considering increased incidence of co-prescriptions and adverse outcomes, policy changes recommending avoidance of concomitant opioid and skeletal muscle relaxant/sedative use are needed. All 14 studies are diverse but showed higher age, higher opioid dose, and South with more coprescription-associated negative outcomes. Overall consistency of negative outcomes needs further investigation of interactions despite limitations. Policymakers, clinicians, and patients should know the risks of concomitant prescribing to solidify current policy recommendations, ensure adequate drug monitoring and co-prescribing controls through prior authorization, reduce number of co-prescriptions, and improve clinical outcomes.