High-risk use by patients prescribed opioids for pain and its role in overdose deaths

JAMA Intern Med. 2014 May;174(5):796-801. doi: 10.1001/jamainternmed.2013.12711.


Importance: From January 1, 2003, through December 31, 2010, drug overdose deaths in Tennessee increased from 422 to 1059 per year. More of these deaths involved prescription opioids than heroin and cocaine combined.

Objective: To assess the contribution of certain opioid-prescribing patterns to the risk of overdose death.

Design, setting, and participants: We performed a matched case-control study that analyzed opioid prescription data from the Tennessee Controlled Substances Monitoring Program (TNCSMP) from January 1, 2007, through December 31, 2011, to identify risk factors associated with opioid-related overdose deaths from January 1, 2009, through December 31, 2010. Case patients were ascertained from death certificate data. Age- and sex-matched controls were randomly selected from among live patients in the TNCSMP.

Main outcomes and measures: We defined a high-risk number of prescribers or pharmacies as 4 or more per year and high-risk dosage as a daily mean of more than 100 morphine milligram equivalents (MMEs) per year. The main outcome was opioid-related overdose death.

Results: From January 1, 2007, through December 31, 2011, one-third of the population of Tennessee filled an opioid prescription each year, and opioid prescription rates increased from 108.3 to 142.5 per 100 population per year. Among all patients in Tennessee prescribed opioids during 2011, 7.6% used more than 4 prescribers, 2.5% used more than 4 pharmacies, and 2.8% had a mean daily dosage greater than 100 MMEs. Increased risk of opioid-related overdose death was associated with 4 or more prescribers (adjusted odds ratio [aOR], 6.5; 95% CI, 5.1-8.5), 4 or more pharmacies (aOR, 6.0; 95% CI, 4.4-8.3), and more than 100 MMEs (aOR, 11.2; 95% CI, 8.3-15.1). Persons with 1 or more risk factor accounted for 55% of all overdose deaths.

Conclusions and relevance: High-risk use of prescription opioids is frequent and increasing in Tennessee and is associated with increased overdose mortality. Use of prescription drug–monitoring program data to direct risk-reduction measures to the types of patients overrepresented among overdose deaths might reduce mortality associated with opioid abuse.

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / poisoning*
  • Case-Control Studies
  • Cause of Death
  • Drug Overdose / epidemiology*
  • Drug Utilization Review
  • Epidemiological Monitoring
  • Female
  • Humans
  • Inappropriate Prescribing / statistics & numerical data
  • Male
  • Opioid-Related Disorders / mortality*
  • Pain / drug therapy*
  • Pharmacies / statistics & numerical data
  • Prescription Drug Misuse / statistics & numerical data*
  • Prescription Drug Misuse / trends
  • Risk
  • Substance-Related Disorders / mortality*
  • Tennessee / epidemiology


  • Analgesics, Opioid