Cohort study of the impact of high-dose opioid analgesics on overdose mortality

Nabarun Dasgupta, Michele Jonsson Funk, Scott Proescholdbell, Annie Hirsch, Kurt M. Ribisl, Steve Marshall

Research output: Contribution to journalArticle

  • 14 Citations

Abstract

Objective. Previous studies examining opioid dose and overdose risk provide limited granularity by milligram strength and instead rely on thresholds. We quantify dose-dependent overdose mortality over a large spectrum of clinically common doses. We also examine the contributions of benzodiazepines and extended release opioid formulations to mortality. Design. Prospective observational cohort with one year follow-up. Setting. One year in one state (NC) using a controlled substances prescription monitoring program, with name-linked mortality data. Subjects. Residential population of North Carolina (n59,560,234), with 2,182,374 opioid analgesic patients. Methods. Exposure was dispensed prescriptions of solid oral and transdermal opioid analgesics; person- years calculated using intent-to-treat principles. Outcome was overdose deaths involving opioid analgesics in a primary or additive role. Poisson models were created, implemented using generalized estimating equations. Results. Opioid analgesics were dispensed to 22.8% of residents. Among licensed clinicians, 89.6% prescribed opioid analgesics, and 40.0% prescribed ER formulations. There were 629 overdose deaths, half of which had an opioid analgesic prescription active on the day of death. Of 2,182,374 patients prescribed opioids, 478 overdose deaths were reported (0.022% per year). Mortality rates increased gradually across the range of average daily milligrams of morphine equivalents. 80.0% of opioid analgesic patients also received benzodiazepines. Rates of overdose death among those co-dispensed benzodiazepines and opioid analgesics were ten times higher (7.0 per 10,000 person-years, 95 percent CI: 6.3, 7.8) than opioid analgesics alone (0.7 per 10,000 person years, 95 percent CI: 0.6, 0.9). Conclusions. Dose-dependent opioid overdose risk among patients increased gradually and did not show evidence of a distinct risk threshold. There is urgent need for guidance about combined classes of medicines to facilitate a better balance between pain relief and overdose risk.

Original languageEnglish (US)
Pages (from-to)85-98
Number of pages14
JournalPain Medicine (United States)
Volume17
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Opioid Analgesics
Cohort Studies
Mortality
Benzodiazepines
Prescriptions
Controlled Substances
Morphine
Pain

Keywords

  • Big Data
  • Chronic Pain
  • Cloud Computing
  • Cohort Study
  • Dose–Response
  • Epidemiology
  • Opioids
  • Overdose
  • Prescriptions
  • Risk Factors

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Cohort study of the impact of high-dose opioid analgesics on overdose mortality. / Dasgupta, Nabarun; Funk, Michele Jonsson; Proescholdbell, Scott; Hirsch, Annie; Ribisl, Kurt M.; Marshall, Steve.

In: Pain Medicine (United States), Vol. 17, No. 1, 01.01.2016, p. 85-98.

Research output: Contribution to journalArticle

Dasgupta, Nabarun; Funk, Michele Jonsson; Proescholdbell, Scott; Hirsch, Annie; Ribisl, Kurt M.; Marshall, Steve / Cohort study of the impact of high-dose opioid analgesics on overdose mortality.

In: Pain Medicine (United States), Vol. 17, No. 1, 01.01.2016, p. 85-98.

Research output: Contribution to journalArticle

@article{8638e07c7bc049fe969e02c7069703e2,
title = "Cohort study of the impact of high-dose opioid analgesics on overdose mortality",
abstract = "Objective. Previous studies examining opioid dose and overdose risk provide limited granularity by milligram strength and instead rely on thresholds. We quantify dose-dependent overdose mortality over a large spectrum of clinically common doses. We also examine the contributions of benzodiazepines and extended release opioid formulations to mortality. Design. Prospective observational cohort with one year follow-up. Setting. One year in one state (NC) using a controlled substances prescription monitoring program, with name-linked mortality data. Subjects. Residential population of North Carolina (n59,560,234), with 2,182,374 opioid analgesic patients. Methods. Exposure was dispensed prescriptions of solid oral and transdermal opioid analgesics; person- years calculated using intent-to-treat principles. Outcome was overdose deaths involving opioid analgesics in a primary or additive role. Poisson models were created, implemented using generalized estimating equations. Results. Opioid analgesics were dispensed to 22.8% of residents. Among licensed clinicians, 89.6% prescribed opioid analgesics, and 40.0% prescribed ER formulations. There were 629 overdose deaths, half of which had an opioid analgesic prescription active on the day of death. Of 2,182,374 patients prescribed opioids, 478 overdose deaths were reported (0.022% per year). Mortality rates increased gradually across the range of average daily milligrams of morphine equivalents. 80.0% of opioid analgesic patients also received benzodiazepines. Rates of overdose death among those co-dispensed benzodiazepines and opioid analgesics were ten times higher (7.0 per 10,000 person-years, 95 percent CI: 6.3, 7.8) than opioid analgesics alone (0.7 per 10,000 person years, 95 percent CI: 0.6, 0.9). Conclusions. Dose-dependent opioid overdose risk among patients increased gradually and did not show evidence of a distinct risk threshold. There is urgent need for guidance about combined classes of medicines to facilitate a better balance between pain relief and overdose risk.",
keywords = "Big Data, Chronic Pain, Cloud Computing, Cohort Study, Dose–Response, Epidemiology, Opioids, Overdose, Prescriptions, Risk Factors",
author = "Nabarun Dasgupta and Funk, {Michele Jonsson} and Scott Proescholdbell and Annie Hirsch and Ribisl, {Kurt M.} and Steve Marshall",
year = "2016",
month = "1",
doi = "10.1111/pme.12907",
volume = "17",
pages = "85--98",
journal = "Pain Medicine (United States)",
issn = "1526-2375",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Cohort study of the impact of high-dose opioid analgesics on overdose mortality

AU - Dasgupta,Nabarun

AU - Funk,Michele Jonsson

AU - Proescholdbell,Scott

AU - Hirsch,Annie

AU - Ribisl,Kurt M.

AU - Marshall,Steve

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Objective. Previous studies examining opioid dose and overdose risk provide limited granularity by milligram strength and instead rely on thresholds. We quantify dose-dependent overdose mortality over a large spectrum of clinically common doses. We also examine the contributions of benzodiazepines and extended release opioid formulations to mortality. Design. Prospective observational cohort with one year follow-up. Setting. One year in one state (NC) using a controlled substances prescription monitoring program, with name-linked mortality data. Subjects. Residential population of North Carolina (n59,560,234), with 2,182,374 opioid analgesic patients. Methods. Exposure was dispensed prescriptions of solid oral and transdermal opioid analgesics; person- years calculated using intent-to-treat principles. Outcome was overdose deaths involving opioid analgesics in a primary or additive role. Poisson models were created, implemented using generalized estimating equations. Results. Opioid analgesics were dispensed to 22.8% of residents. Among licensed clinicians, 89.6% prescribed opioid analgesics, and 40.0% prescribed ER formulations. There were 629 overdose deaths, half of which had an opioid analgesic prescription active on the day of death. Of 2,182,374 patients prescribed opioids, 478 overdose deaths were reported (0.022% per year). Mortality rates increased gradually across the range of average daily milligrams of morphine equivalents. 80.0% of opioid analgesic patients also received benzodiazepines. Rates of overdose death among those co-dispensed benzodiazepines and opioid analgesics were ten times higher (7.0 per 10,000 person-years, 95 percent CI: 6.3, 7.8) than opioid analgesics alone (0.7 per 10,000 person years, 95 percent CI: 0.6, 0.9). Conclusions. Dose-dependent opioid overdose risk among patients increased gradually and did not show evidence of a distinct risk threshold. There is urgent need for guidance about combined classes of medicines to facilitate a better balance between pain relief and overdose risk.

AB - Objective. Previous studies examining opioid dose and overdose risk provide limited granularity by milligram strength and instead rely on thresholds. We quantify dose-dependent overdose mortality over a large spectrum of clinically common doses. We also examine the contributions of benzodiazepines and extended release opioid formulations to mortality. Design. Prospective observational cohort with one year follow-up. Setting. One year in one state (NC) using a controlled substances prescription monitoring program, with name-linked mortality data. Subjects. Residential population of North Carolina (n59,560,234), with 2,182,374 opioid analgesic patients. Methods. Exposure was dispensed prescriptions of solid oral and transdermal opioid analgesics; person- years calculated using intent-to-treat principles. Outcome was overdose deaths involving opioid analgesics in a primary or additive role. Poisson models were created, implemented using generalized estimating equations. Results. Opioid analgesics were dispensed to 22.8% of residents. Among licensed clinicians, 89.6% prescribed opioid analgesics, and 40.0% prescribed ER formulations. There were 629 overdose deaths, half of which had an opioid analgesic prescription active on the day of death. Of 2,182,374 patients prescribed opioids, 478 overdose deaths were reported (0.022% per year). Mortality rates increased gradually across the range of average daily milligrams of morphine equivalents. 80.0% of opioid analgesic patients also received benzodiazepines. Rates of overdose death among those co-dispensed benzodiazepines and opioid analgesics were ten times higher (7.0 per 10,000 person-years, 95 percent CI: 6.3, 7.8) than opioid analgesics alone (0.7 per 10,000 person years, 95 percent CI: 0.6, 0.9). Conclusions. Dose-dependent opioid overdose risk among patients increased gradually and did not show evidence of a distinct risk threshold. There is urgent need for guidance about combined classes of medicines to facilitate a better balance between pain relief and overdose risk.

KW - Big Data

KW - Chronic Pain

KW - Cloud Computing

KW - Cohort Study

KW - Dose–Response

KW - Epidemiology

KW - Opioids

KW - Overdose

KW - Prescriptions

KW - Risk Factors

UR - http://www.scopus.com/inward/record.url?scp=84940930142&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940930142&partnerID=8YFLogxK

U2 - 10.1111/pme.12907

DO - 10.1111/pme.12907

M3 - Article

VL - 17

SP - 85

EP - 98

JO - Pain Medicine (United States)

T2 - Pain Medicine (United States)

JF - Pain Medicine (United States)

SN - 1526-2375

IS - 1

ER -