Opioid Dose Variability May Be a Risk Factor for Overdose

There is an apparent dose-response association between variability in opioid dose and overdose risk, according to a study published in JAMA Network Open.

“Our study suggests that safely managing long-term opioid therapy is complex,” said Ingrid Binswanger, MD, Institute for Health Research, Kaiser Permanente Colorado, Aurora, Colorado.

“This study suggests [that] dose variability could present an increased risk of overdose,” she continued. “We also found [that] eventually discontinuing opioid therapy may prevent overdoses.”

For the study, Jason M. Glanz, PhD, Institute for Health Research, Kaiser Permanente Colorado, and colleagues examined the effect of opioid dose variability on 228 patients with incident opioid overdose and 3,547 controls who were prescribed long-term opioid therapy. The mean duration of opioid therapy was 36.7 months in patients who experienced an overdose and 33 months in controls.

The researchers found that individuals exposed to the highest category of dose variability had an odds ratio of 3.32 (95% confidence interval [CI], 1.63-6.77) for experiencing an overdose compared with individuals exposed to the lowest category of dose variability.

Individuals prescribed high doses (>100 mg of morphine equivalents) in the 3 months before the index date had an odds ratio of 2.37 (95% CI, 1.41-3.98) for experiencing an overdose compared with individuals prescribed lower doses (0-20 mg of morphine equivalents).

The analysis evaluating variability in dose as dose response was statistically significant.

Without dose variability in the model, an opioid dose >100 mg of morphine equivalents was associated with a higher risk of overdose (odds ratio [OR] = 3.10; 95% CI, 1.85-5.19) compared with a dose of 0 to 20 mg of morphine equivalents.

An interaction was not found between dose and variability in dose, suggesting that the association of dose variability with overdose risk did not vary by the magnitude of dose.

Individuals with sustained opioid therapy discontinuation (defined as 3 continuous months with 0 mg of morphine equivalents before the index date) were 51% less likely to have experienced an overdose than those who had not discontinued opioid therapy (OR = 0.49; 95% CI, 0.26-0.93).

“This study represents the first of many investigations that we plan to do on [this] topic,” concluded Dr. Glanz. “Our goal is to help identify safe and effective approaches for managing long-term opioid therapy. We want to be able to minimise patients’ pain and reduce their risk of overdose.”