Duration of Opioid Action Affects Unintentional Overdoses

BOSTON — Clinicians weighing the risks and benefits of prescribing different opioid regimens should take not only the daily dose into consideration but also the duration of the opioid action, according to a new study.

That study, published recently in JAMA Internal Medicine, suggests that favoring short-acting agents whenever possible, especially during the first two weeks of therapy, could lower the risk of unintentional overdose events.1

The authors from the VA Boston Healthcare System, Northeastern University and the Harvard Medical School, all in Boston, point out that “few controlled studies have examined the extent to which ecologic measures of increases in opioid prescribing and overdose injuries reflect risk among patients prescribed opioids, let alone whether some opioid regimens are safer than others.”

Yet, they add, “The unprecedented increase in unintentional overdose events that has occurred in tandem with escalating sales of prescription opioids over the past two decades has raised concerns about whether the therapeutic use of opioids has contributed to increases in overdose injury.”

To examine whether the risk of unintentional overdose injury is associated with the duration of opioid action, the researchers conducted a propensity score-adjusted cohort study using population-based healthcare utilization data from the VHA. Patients were veterans with chronic painful conditions who began therapy with opioid analgesics between Jan. 1, 2000, and Dec. 31, 2009.

With 319 unintentional overdose events observed, patients initiating therapy with long-acting opioids were found to be more than twice as likely to overdose compared with persons initiating therapy with short-acting opioids.

After adjustment for age, sex, opioid dose and other clinical characteristics, patients receiving long-acting opioids had a significantly higher rate of overdose injury — hazard ratio 2.33 — than did those receiving short-acting opioids. The authors noted that the risk associated with long-acting agents was particularly marked during the first two weeks after initiation of treatment, with a hazard ratio of 5.25.

“To our knowledge, the findings of the present study provide the first evidence that the risk of unintentional overdose injury is related to the prescribed opioid’s duration of action,” the study concludes. “If replicated in other cohorts, our findings suggest that clinicians weighing the benefits and risks of initiating different opioid regimens should consider not only the daily dose prescribed but also the duration of opioid action, favoring short-acting agents whenever possible, especially during the first two weeks of therapy.”

1 Miller M, Barber CW, Leatherman S, Fonda J, Hermos JA, Cho K, Gagnon DR. Prescription opioid duration of action and the risk of unintentional overdose among patients receiving opioid therapy. JAMA Intern Med. 2015 Apr1;175(4):608-15. doi: 10.1001/jamainternmed.2014.8071. PubMed PMID: 25686208.

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