Opioids + Comorbidities = Trouble?

The increase in opioid prescribing for non-cancer pain has drawn attention to the corresponding increase in unintentional overdose deaths.

However, opioids also cause or exacerbate sleep-disordered breathing, boost the risk of adverse cardiovascular events, and cause adverse psychomotor, endocrine, gastrointestinal, and immunologic effects. Researchers have recently conducted limited population-based studies comparing opioid alternatives, such as analgesic anticonvulsants and low-dose cyclic antidepressants.

The Journal of the American Medical Association has published a study in its June 2016 issue that shows long-acting opioids increase all-cause mortality compared to non-opioid treatments for moderate to severe chronic non-cancer pain.

The researchers conducted a retrospective cohort study of Tennessee Medicaid patients with chronic non-cancer pain. Patients had moderate-to-severe chronic pain, and had been prescribed either long-acting opioids or alternative medications.

Patients treated with long-acting opioid were 64% more likely to die than matched patients who were treated with other options. This coincides with an additional 69 deaths per 10,000 patient-years. More than two-thirds of these excess deaths were not overdose-related.

Most of the non-overdose deaths were cardiovascular in character, and respiratory depression and sleep-disordered breathing compound cardiovascular risk.

Misclassification of cause of death on death certificates may have biased the results. This also raises suspicion that other studies may have underestimated the risk of opioids. Overdose risk was artificially low in this study because the researchers excluded patients with a history of drug abuse.

As such the authors concluded, long-acting opioids increase all-cause mortality, including non-overdose related deaths, compared to anticonvulsants and cyclic antidepressants. Furthermore, providers should consider the excess risk of death when weighing the benefits and harms of treatments.