Risk of unintentional overdose higher for long-acting opioids

Patients taking long-acting opioids are more than twice as likely to overdose unintentionally than patients taking short-acting opioids, study finds.

Long-acting opioids may carry a higher risk for unintentional overdose than short-acting formulations, study suggests. Morphine sulphate tablets pictured

Long-acting opioids may carry a higher risk for unintentional overdose than short-acting formulations, suggests a US cohort study published in JAMA Internal Medicine
on 16 February 2015.

In a propensity-score-adjusted analysis, people initiating treatment with long-acting opioids for the management of chronic pain were more than twice as likely to overdose compared with those initiating short-acting drugs. The risk was particularly high in the first two weeks after starting treatment.

The researchers, led by Matthew Miller from Northeastern University, Boston, Massachusetts, believe their findings provide the first evidence that the risk of unintentional opioid overdose injury is related to the prescribed drug’s duration of action.

“If replicated in other cohorts, our findings suggest that clinicians weighing the benefits and risks of different opioid regimens should take into account not only the daily dose prescribed but also the duration of opioid action, favouring short-acting opioids whenever possible, especially during the first two weeks after initiation of therapy,” the researchers say.

Miller’s team analysed information on 319 patients in the Veterans Administrations Healthcare System who had experienced an unintentional opioid overdose (defined as drug or medication poisoning of accidental or undetermined intent). All patients had been prescribed an opioid for chronic non-cancer pain.

Most of the overdoses were in patients taking short-acting opioids, with 37 involving long-acting drugs; around half of all events occurred within the first 60 days of starting treatment. After adjusting for covariates, overdose was more likely for patients taking long-acting versus short-acting opioids, with a hazard ratio of 2.33 (95% confidence interval [CI] 1.26–4.32).

The risk for overdose was particularly marked in the first fortnight after initiating therapy, with a hazard ratio of 5.25 (95% CI 1.88–14.72). The risk was also greater for patients initiating higher-dose opioids (50mg morphine equivalents) compared with those receiving lower doses (1mg–20mg equivalents).

“The exceptionally high relative risk observed during the first two weeks of therapy was driven by a very high rate of unintentional overdose injury among patients receiving long-acting agents rather than a particularly low rate of injury among those receiving short-acting agents, making it less likely that differentially poor initial adherence to opioid therapy by patients receiving short-acting agents accounts for our findings,” the researchers remark. 


[1] Miller M, Barber CW, Leatherman S et al. Prescription opioid duration of action and the risk of unintentional overdose among patients receiving opioid therapy. JAMA Internal Medicine 2015. doi: 10.1001/jamainternmed.2014.8071.

Last updated
The Pharmaceutical Journal, PJ, 7 March 2015, Vol 294, No 7852;294(7852):DOI:10.1211/PJ.2015.20067928

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