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Prescription of long-acting opioids associated with increased risk of death

June 14, 2016

Prescription of long-acting opioids for chronic noncancer pain was associated with an increased risk of all-cause mortality, including deaths from causes other than overdose, compared with anticonvulsants or cyclic antidepressants, according to a study appearing in the June 14, 2016 issue of JAMA.

The increase in prescribing opioid analgesics for chronic noncancer pain has led to escalating concern about potential harms. Long-acting opioids increase the risk of unintentional overdose deaths but also may increase mortality from cardiorespiratory and other causes. Wayne A. Ray, Ph.D., of the Vanderbilt University School of Medicine, Nashville, Tenn., and colleagues compared the risk of death among patients initiating long-acting opioid therapy for moderate to severe chronic noncancer pain with that for matched patients initiating therapy with either an analgesic anticonvulsant or a low-dose cyclic antidepressant (medications that served as a control arm). The study included Tennessee Medicaid patients with chronic noncancer pain and no evidence of palliative or end-of-life care (1999 - 2012).

There were 22,912 new episodes of prescribed therapy for both long-acting opioids and control medications. The long-acting opioid group was followed up for an average 176 days and had 185 deaths and the control treatment group was followed up for an average 128 days and had 87 deaths. Analysis indicated that patients prescribed therapy for a long-acting opioid had a risk of all-cause mortality that was 1.6 times greater than that for matched patients starting an analgesic anticonvulsant or a low-dose cyclic antidepressant. The absolute risk difference was modest. The difference was explained by a 1.9 times greater risk of out-of-hospital deaths. More than two-thirds of the excess deaths were due to causes other than unintentional overdose; of these, more than one-half were cardiovascular deaths. The increased risk was confined to the first 180 days of prescribed therapy but was present for long-acting opioid doses of 60 mg or less of morphine-equivalents.

"These findings should be considered when evaluating harms and benefits of treatment," the authors write.
(doi:10.1001/jama.2016.7789; this study is available pre-embargo at the For The Media website.)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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