As health care providers lower opioid doses for pain patients to minimize the risk of addiction; increase doses to manage worsening pain; or re-start dosing after a period of time without opioid pain relievers, patients could be getting confused about safe dose levels, putting them at risk for overdose. A new study funded by the National Institute on Drug Abuse found that high dose variability increases the odds for an opioid overdose independent of dose alone. Even among patients receiving low doses of opioids, dose variability increases the risk of overdose.

The study followed long-term opioid therapy patients enrolled in Kaiser Permanente Colorado, from January 1, 2006 to December 31, 2017. The study matched 228 patients who had experienced an opioid overdose with 3,547 control patients who had not experienced an opioid overdose.

Results suggested that more dose variability correlates with a more than three-fold increase in overdose risk. The authors suggested patients in long-term opioid therapy are exposed to changes in dose for a variety of reasons, including worsened pain, practitioner-initiated tapers, changing physicians, missed appointments, poor adherence to urine toxicology screening, or travel. The periods of greatest risk could follow abrupt changes in dosage, such as resuming opioid use after a period with no pain reliever use, prompting patients to seek a dose that may heighten their risk for overdose. Alternatively, a dose reduction may cause patients to seek pharmaceutical opioids from other sources.

These findings suggest that practitioners should: seek to minimize dose variability when managing long-term opioid therapy; pursue careful dose monitoring; and exercise caution in designing and implementing policies to reduce opioid prescribing. Tapering patients off long-term opioid therapy may be beneficial if it ultimately leads to the discontinuation of opioid therapy, but it also may result in dose variability associated with an increased risk of overdose.

The National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, funded this study. Investigators at Kaiser Permanente’s Institute for Health Research led the research team.

For a copy of the article, published in JAMA Network Open, go to Association Between Opioid Dose Variability and Opioid Overdose Among Adults Prescribed Long-term Opioid Therapy.

For more information about opioid overdoses, visit NIDA’s Opioid Overdose Crisis Webpage.

For more information, contact the NIDA press office at media@nida.nih.gov or 301-443-6245. Follow NIDA on Twitter and Facebook.

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