Prescription of long-acting opioid medications for chronic, noncancer pain is associated with an increased risk of all-cause mortality when compared to alternative medications, according to research published in JAMA.

Wayne A. Ray, PhD, Vanderbilt University School of Medicine, Nashville, and colleagues conducted a retrospective cohort study of Tennessee Medicaid patients with chronic, noncancer pain between 1999 and 2012. Patients had received either long-acting opioid therapy or comparable therapy with either an analgesic anticonvulsant or low-dose cyclic antidepressant. Patients had not received palliative or end-of-life care.

The researchers found 22,912 new episodes of prescribed therapy for both long-acting opioids and control medications; 185 deaths were recorded in the long-acting opioid group, compared to 87 deaths recorded in the control group. Data analysis showed that patients who were prescribed long-acting opioid therapy had a 1.6 times greater risk of all-cause mortality and a 1.9 times greater risk of out-of-hospital death.

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“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,” noted Dr Ray. “These findings should be considered when evaluating harms and benefits of treatment.”


  1. Ray WA, Chung CP, Murray KT, et al. Prescription of long-acting opioids and mortality in patients with chronic noncancer pain. JAMA. 2016;315(22):2415-2423; doi: 10.1001/jama.2016.7789