Opioid Analgesic Prescribing and Overdose Mortality in North Carolina Public Deposited

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  • March 22, 2019
Creator
  • Dasgupta, Nabarun
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • Mortality from drug overdose has risen since the 1990s. Composite International Classification of Disease (ICD-10) overdose definitions in state vital statistics surveillance may include deaths that do not involve controlled substances while missing deaths that do. We evaluated seven ICD-10-based definitions using North Carolina mortality data from 2008 through 2011. Overdose deaths varied by definition, ranging from 734 to 1,202 per year. Up to 16.1% of deaths using the national definition showed no evidence of controlled substance involvement, however, additional deaths involving controlled substances were not identified. We propose a definition that includes deaths from substance use disorders, but removes deaths from pharmaceutical adverse events, resulting in 1,149 deaths per year from overdoses involving controlled substances. Strong associations have been observed between amount of opioids dispensed and overdose mortality. Yet, clinical trials consistently show safety of opioid analgesics at high doses. To explore this paradox we conducted a prospective cohort study among North Carolina residents in 2010 to quantify dose-dependent overdose risk in routine clinical practice. Dispensing data were matched to overdose deaths identified in medical examiner records. Incidence rates were estimated using regression models. Exposure of 1,133,957 person-years to opioid analgesics was observed, corresponding to 22.8% of residents. Incidence rates appeared to increase gradually at lower doses, but stayed elevated beyond 200 mg average daily milligrams of morphine equivalents. The dose-dependent effect was exacerbated by co-prescribed central nervous system (CNS) depressants; rates were ten times higher among opioid analgesic patients receiving benzodiazepines. Since 80% of patients were co-prescribed benzodiazepines, high dose opioid analgesic use during routine clinical practice was more risky than observed in trials that exclude patients receiving other CNS depressants. Exploring formulation impacts, incidence rates were ten times greater among those receiving combinations of extended-release (ER) and immediate-release (IR) opioid analgesics compared to those receiving only IR. At higher doses, for every 1,300 patients treated for a year with ER instead of IR, there would be one additional overdose death. As a society we urgently need to understand what level of prescribing would strike the correct balance between access to care concerns and inadequately trained physicians.
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  • In Copyright
Advisor
  • Marshall, Stephen
Degree
  • Doctor of Philosophy
Graduation year
  • 2013
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