Risk of Opioid Overdose Associated With Concomitant Use of Opioids and Skeletal Muscle Relaxants: A Population-Based Cohort Study.
Adult
Analgesics, Opioid
/ administration & dosage
Baclofen
/ administration & dosage
Benzodiazepines
/ administration & dosage
Carisoprodol
/ administration & dosage
Cohort Studies
Drug Interactions
Female
Humans
Male
Middle Aged
Neuromuscular Agents
/ administration & dosage
Opiate Overdose
/ epidemiology
Practice Patterns, Physicians'
Retrospective Studies
Time Factors
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
18
10
2019
accepted:
28
01
2020
pubmed:
6
2
2020
medline:
17
2
2021
entrez:
6
2
2020
Statut:
ppublish
Résumé
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.
Substances chimiques
Analgesics, Opioid
0
Neuromuscular Agents
0
Benzodiazepines
12794-10-4
Carisoprodol
21925K482H
Baclofen
H789N3FKE8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
81-89Informations de copyright
© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.
Références
Scholl, L., Seth, P., Kariisa, M., Wilson, N. & Baldwin, G. Drug and opioid-involved overdose deaths - United States, 2013-2017. MMWR Morb. Mortal. Wkly. Rep. 67, 1419-1427 (2018).
Rudd, R.A., Aleshire, N., Zibbell, J.E. & Gladden, R.M. Increases in drug and opioid overdose deaths-United States, 2000-2014. MMWR Morb. Mortal. Wkly. Rep. 64, 1378-1382 (2016).
Hedegaard, H., Miniño, A. & Warner, M. Drug overdose deaths in the United States, 1999-2017. NCHS Data Brief, No. 329. (National Center for Health Statistics, Hyattsville, MD, 2018).
Dart, R.C. et al. Trends in opioid analgesic abuse and mortality in the United States. N Engl. J. Med. 372, 241-248 (2015).
US Food and Drug Administration. FDA drug safety communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning <https://www.fda.gov/Drugs/DrugSafety/ucm518473.htm> (2016). Accessed August 15, 2018.
Zin, C.S. & Ismail, F. Co-prescription of opioids with benzodiazepine and other co-medications among opioid users: differential in opioid doses. J. Pain. Res. 10, 249-257 (2017).
Nadpara, P.A. et al. Risk factors for serious prescription opioid-induced respiratory depression or overdose: comparison of commercially insured and Veterans Health Affairs populations. Pain. Med. 19, 79-96 (2018).
Dowell, D., Haegerich, T.M. & Chou, R. CDC guideline for prescribing opioids for chronic pain-United States, 2016. JAMA 315, 1624-1645 (2016).
White, J.M. & Irvine, R.J. Mechanisms of fatal opioid overdose. Addiction 94, 961-972 (1999).
Gomes, T., Mamdani, M.M., Dhalla, I.A., Paterson, J.M. & Juurlink, D.N. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch. Intern. Med. 171, 686-691 (2011).
Sun, E.C., Dixit, A., Humphreys, K., Darnall, B.D., Baker, L.C. & Mackey, S. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ 356, j760 (2017).
Park, T.W., Saitz, R., Ganoczy, D., Ilgen, M.A. & Bohnert, A.S.B. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ 350, h2698 (2015).
Jones, J.D., Mogali, S. & Comer, S.D. Polydrug abuse: a review of opioid and benzodiazepine combination use. Drug Alcohol Depend 125, 8-18 (2012).
See, S. & Ginzburg, R. Skeletal muscle relaxants. Pharmacotherapy 28, 207-213 (2008).
Garg, R.K., Fulton-Kehoe, D. & Franklin, G.M. Patterns of opioid use and risk of opioid overdose death among Medicaid patients. Med. Care 55, 661-668 (2017).
Mosher, H.J., Richardson, K.K. & Lund, B.C. Sedative prescriptions are common at opioid initiation: an observational study in the Veterans Health Administration. Pain Med. 19, 788-792 (2017).
Larochelle, M.R., Zhang, F., Ross-Degnan, D. & Wharam, J.F. Trends in opioid prescribing and co-prescribing of sedative hypnotics for acute and chronic musculoskeletal pain: 2001-2010. Pharmacoepidemiol. Drug Saf. 24, 885-892 (2015).
Brat, G.A. et al. Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study. BMJ 360, j5790 (2018).
Samples, H., Williams, A.R., Olfson, M. & Crystal, S. Risk factors for discontinuation of buprenorphine treatment for opioid use disorders in a multi-state sample of Medicaid enrollees. J. Subst. Abuse Treat. 95, 9-17 (2018).
Green, C.A., Perrin, N.A., Janoff, S.L., Campbell, C.I., Chilcoat, H.D. & Coplan, P.M. Assessing the accuracy of opioid overdose and poisoning codes in diagnostic information from electronic health records, claims data, and death records. Pharmacoepidemiol. Drug Saf. 26, 509-517 (2017).
Austin, P.C. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav. Res. 46, 399-424 (2011).
Austin, P.C. & Stuart, E.A. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat. Med. 34, 3661-3679 (2015).
Kurth, T. et al. Results of multivariable logistic regression, propensity matching, propensity adjustment, and propensity-based weighting under conditions of nonuniform effect. Am. J. Epidemiol. 163, 262-270 (2006).
Austin, P.C. Using the standardized difference to compare the prevalence of a binary variable between two groups in observational research. Commun. Stat. Simul. Comput. 38, 1228-1234 (2009).
Austin, P.C. Variance estimation when using inverse probability of treatment weighting (IPTW) with survival analysis. Stat. Med. 35, 5642-5655 (2016).
Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (The Cochrane Collaboration, London, UK, 2011).
Cochran, G. et al. Medicaid prior authorization and opioid medication abuse and overdose. Am. J. Manag. Care 23, e164-171 (2017).
Center for Behavioral Health Statistics and Quality. 2015 National Survey on Drug Use and Health: Detailed Tables (Substance Abuse and Mental Health Services Administration, Rockville, MD, 2016).
Cohen, R.I. et al. Role of muscle relaxants in the treatment of pain. In Comprehensive Treatment of Chronic Pain by Medical, Interventional, and Integrative Approaches (eds. Deer, T.R. et al.) (Springer-Verlag, New York, NY, 2013).
See, S. & Ginzburg, R. Choosing a skeletal muscle relaxant. Am. Fam. Phys. 78, 365-370 (2008).
Moody, D.E., Fu, Y. & Fang, W.B. Inhibition of in vitro metabolism of opioids by skeletal muscle relaxants. Basic Clin. Pharmacol. Toxicol. 123, 327-334 (2018).
Horsfall, J.T. & Sprague, J.E. The pharmacology and toxicology of the 'Holy Trinity'. Basic Clin. Pharmacol. Toxicol. 120, 115-119 (2017).
Massei, R., Songa, V. & Trazzi, R. Potentiation of opiates by administration of baclofen and proglumide during the intraoperative period [in Italian]. Minerva Anestesiol. 54, 137-140 (1988).
Olivier, P.-Y. et al. Severe central sleep apnea associated with chronic baclofen therapy: a case series. Chest 149, e127-e131 (2016).
Chaignot, C., Zureik, M., Rey, G., Dray-Spira, R., Coste, J. & Weill, A. Risk of hospitalisation and death related to baclofen for alcohol use disorders: comparison with nalmefene, acamprosate, and naltrexone in a cohort study of 165 334 patients between 2009 and 2015 in France. Pharmacoepidemiol. Drug Saf. 27, 1239-1248 (2018).
van Tulder, M.W., Touray, T., Furlan, A.D., Solway, S. & Bouter, L.M. Muscle relaxants for non-specific low back pain. Cochrane Database Syst. Rev. CD004252 (2003).
Chou, R., Peterson, K. & Helfand, M. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. J. Pain Symptom. Manage. 28, 140-175 (2004).
Flexeril [package insert]. (McNeil Consumer Healthcare, Fort Washington, PA, 2013).
Park, T.W., Lin, L.A., Hosanagar, A., Kogowski, A., Paige, K. & Bohnert, A.S. Understanding risk factors for opioid overdose in clinical populations to inform treatment and policy. J. Addict. Med. 10, 369-381 (2016).
Dunn, K.M. et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann. Intern. Med. 152, 85-92 (2010).
Sullivan, D., Lyons, M., Montgomery, R. & Quinlan-Colwell, A. Exploring opioid-sparing multimodal analgesia options in trauma: a nursing perspective. J. Trauma Nurs. 23, 361-375 (2016).
Wang, Y., Delcher, C., Li, Y., Goldberger, B.A. & Reisfield, G.M. Overlapping prescriptions of opioids, benzodiazepines, and carisoprodol: "Holy Trinity" prescribing in the state of Florida. Drug Alcohol Depend 205, 107693 (2019).
Adelmann, P.K. Mental and substance use disorders among Medicaid recipients: prevalence estimates from two national surveys. Adm. Policy Ment. Health 31, 111-129 (2003).
Centers for Disease Control and Prevention. Overdose deaths involving prescription opioids among Medicaid enrollees - Washington, 2004-2007. MMWR Morb. Mortal. Wkly. Rep. 58, 1171-1175 (2009).
Whitmire, J.T. & Adams, G.W. Unintentional overdose deaths in the North Carolina Medicaid population prevalence, prescription drug use, and medical care services. SCHS Studies 162, 1-12 (2010).
American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults. J. Am. Geriatr. Soc. 63, 2227-2246 (2015).
Luo, X., Pietrobon, R., Curtis, L.H. & Hey, L.A. Prescription of nonsteroidal anti-inflammatory drugs and muscle relaxants for back pain in the United States. Spine 29, E531-E537 (2004).
Gnjidic, D., Du, W., Pearson, S.-A., Hilmer, S.N. & Banks, E. Ascertainment of self-reported prescription medication use compared with pharmaceutical claims data. Public Health Res. Pract. 27, e27341702 (2017).
Miller, M. et al. Prescription opioid duration of action and the risk of unintentional overdose among patients receiving opioid therapy. JAMA Intern. Med. 175, 608-615 (2015).
Bohnert, A.S.B. et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA 305, 1315-1321 (2011).