Naloxone Co-prescription Associated with Fewer Opioid-Related Emergency Department Visits in Patients Receiving Opioid Medications for Chronic Pain

EBM Focus - Volume 11, Issue 27

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Reference - NOSE study (Ann Intern Med 2016 Jun 28 early online) (level 2 [mid-level] evidence)

  • Naloxone is typically given as a rescue medication in patient with an illicit drug overdose, but naloxone may also may also reduce opioid-related mortality in patients prescribed long-term opioid analgesics.
  • In this study, naloxone co-prescription was associated with a significant reduction in opioid-related emergency department visits at 6-months and 1-year in patients prescribed long-term opioids including oxycodone, hydrocodone or morphine.
  • Co-prescribing naloxone may be a safe and effective way to reduce potential opioid overdoses in patients on long-term opioid therapy, especially those requiring higher doses of opioids.

Opioid prescriptions for adults with chronic pain are associated with significant rates of mortality and emergency department visits, especially in patients requiring higher doses (JAMA 2016 Jun 14;315(22):2415, JAMA 2011 Apr 6;305(13):1315). Naloxone distribution programs providing the opioid antagonist as a rescue medication to illicit drug users (mainly heroin) to be used in case of opioid overdoses have successfully reduced opioid-related mortality in many communities (BMJ 2013 Jan 30;346:f174, MMWR Morb Mortal Wkly Rep 2015 Jun 19;64(23):631). However, these programs have not targeted patients with prescriptions for chronic opioid analgesics. A recent cohort study evaluated 1,985 patients (mean age 57 years) prescribed long-term opioid therapy for the management of chronic pain at 6 primary care clinics in San Francisco, California to assess the ability of naloxone to reduce adverse events in these patients.

The most commonly prescribed opioids included oxycodone (46.2%), hydrocodone (26%), and morphine (25.3%). Seventy-one percent of patients had a daily morphine-equivalent dose ≥ 21 mg and 9.3% had a daily dose ≥ 400 mg morphine-equivalent. Naloxone was co-prescribed in 38.2%, with prescriptions for naloxone significantly more common in patients with higher daily opioid doses or an opioid-related emergency department visit in the prior 12 months. Older patients were significantly less likely to receive naloxone. Overall, 471 opioid-related emergency department visits occurred. Compared to no naloxone prescription, naloxone co-prescription was associated with significantly fewer opioid-related emergency department visits at both 6 months post-prescription (incidence rate ratio 0.53, 95% CI 0.34-0.83) and at 1 year post-prescription (incidence rate ratio 0.37, 95% CI 0.22-0.64). There were no significant differences between groups in the net change in opioid dose over time.

The results of this study suggest that co-prescribing naloxone with long-term opioid medication may prevent opioid overdoses. However, the details of how this reduction occurred could not be easily determined. Naloxone prescriptions and educational material were provided to patients, but it is unknown if the drug itself or increased awareness of the risks of opioid overdose were responsible for the decline in emergency department visits. Additionally, naloxone must be delivered by an observer and having someone else aware of the potential for overdose may also influence the rates of emergency room visits in two ways: a heightened consciousness of the risk for an overdose could lead to closer monitoring of use to stay within prescribed limits and increased alertness to the signs of an overdose may lead to a faster response if one occurs. Regardless of the specific mechanism at work, co-prescribing naloxone appears to be a safe and effective way to reduce potential opioid overdoses in patients on long-term opioid therapy.

For more information, see the Opioids for chronic pain and Opioid overdose topics in DynaMed Plus. DynaMed users click here and here.


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