Nabarun Dasgupta|Michele Jönsson Funk|Scott Proescholdbell|Annie Hirsch|Kurt M. Ribisl|Stephen W. Marshall
Cohort Study of the Impact of High-dose Opioid Analgesics on Overdose Mortality
University of North Carolina at Chapel Hill|University of North Carolina at Chapel Hill|NC Department of Health and Human Services|North Carolina Division of Public Health|North Carolina Division of Public Health|University of North Carolina at Chapel Hill|University of North Carolina at Chapel Hill
objective previous studies examining opioid dose overdose risk provide limited granularity milligram strength instead rely thresholds quantify dosedependent overdose mortality large spectrum clinically common doses also examine contributions benzodiazepines extended release opioid formulations mortality design prospective observational cohort one year followup setting one year one state nc using controlled substances prescription monitoring program namelinked mortality data subjects residential population north carolina n 9560234 2182374 opioid analgesic patients methods exposure dispensed prescriptions solid oral transdermal opioid analgesics personyears calculated using intenttotreat principles outcome overdose deaths involving opioid analgesics primary additive role poisson models created implemented using generalized estimating equations results opioid analgesics dispensed 228 residents among licensed clinicians 896 prescribed opioid analgesics 400 prescribed er formulations 629 overdose deaths half opioid analgesic prescription active day death 2182374 patients prescribed opioids 478 overdose deaths reported 0022 per year mortality rates increased gradually across range average daily milligrams morphine equivalents 800 opioid analgesic patients also received benzodiazepines rates overdose death among codispensed benzodiazepines opioid analgesics ten times higher 70 per 10000 personyears 95 percent ci 63 78 opioid analgesics alone 07 per 10000 person years 95 percent ci 06 09 conclusions dosedependent opioid overdose risk among patients increased gradually show evidence distinct risk threshold urgent need guidance combined classes medicines facilitate better balance pain relief overdose risk