Nonrandomized Intervention Study of Naloxone Coprescription for Primary Care Patients Receiving Long-Term Opioid Therapy for Pain

Ann Intern Med. 2016 Aug 16;165(4):245-52. doi: 10.7326/M15-2771. Epub 2016 Jun 28.


Background: Unintentional overdose involving opioid analgesics is a leading cause of injury-related death in the United States.

Objective: To evaluate the feasibility and effect of implementing naloxone prescription to patients prescribed opioids for chronic pain.

Design: 2-year nonrandomized intervention study.

Setting: 6 safety-net primary care clinics in San Francisco, California.

Participants: 1985 adults receiving long-term opioid therapy for pain.

Intervention: Providers and clinic staff were trained and supported in naloxone prescribing.

Measurements: Outcomes were proportion of patients prescribed naloxone, opioid-related emergency department (ED) visits, and prescribed opioid dose based on chart review.

Results: 38.2% of 1985 patients receiving long-term opioids were prescribed naloxone. Patients prescribed higher doses of opioids and with an opioid-related ED visit in the past 12 months were independently more likely to be prescribed naloxone. Patients who received a naloxone prescription had 47% fewer opioid-related ED visits per month in the 6 months after receipt of the prescription (incidence rate ratio [IRR], 0.53 [95% CI, 0.34 to 0.83]; P = 0.005) and 63% fewer visits after 1 year (IRR, 0.37 [CI, 0.22 to 0.64]; P < 0.001) compared with patients who did not receive naloxone. There was no net change over time in opioid dose among those who received naloxone and those who did not (IRR, 1.03 [CI, 0.91 to 1.27]; P = 0.61).

Limitation: Results are observational and may not be generalizable beyond safety-net settings.

Conclusion: Naloxone can be coprescribed to primary care patients prescribed opioids for pain. When advised to offer naloxone to all patients receiving opioids, providers may prioritize those with established risk factors. Providing naloxone in primary care settings may have ancillary benefits, such as reducing opioid-related adverse events.

Primary funding source: National Institutes of Health.

Publication types

  • Clinical Study
  • Multicenter Study

MeSH terms

  • Adult
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use*
  • Chronic Pain / drug therapy*
  • Drug Overdose / etiology
  • Drug Overdose / prevention & control*
  • Emergency Service, Hospital / statistics & numerical data
  • Female
  • Humans
  • Male
  • Middle Aged
  • Naloxone / therapeutic use*
  • Narcotic Antagonists / therapeutic use*
  • Primary Health Care*
  • San Francisco


  • Analgesics, Opioid
  • Narcotic Antagonists
  • Naloxone