Study Suggests Long-Acting Opioids Increase Risk of Non-Overdose Death

Patients initiating long-acting opioids for chronic noncancer pain may be at a greater risk of cardiovascular and non-overdose death compared with those initiating anticonvulsants or low-dose cyclic antidepressants, according to a report published Tuesday in JAMA. The findings, the authors wrote, add to the growing body of evidence to support non-opioid therapy for the treatment of chronic pain.

Although long-acting opioids increase the risk of unintentional overdose, few studies have examined their overall safety relative to other medications commonly prescribed to treat non-cancer pain.  

Researchers from Vanderbilt University conducted a retrospective cohort study of Tennessee Medicaid enrollees initiating drug therapy for chronic pain from 1999 to 2012. The study drugs were the long-acting opioids (sustained-release [SR] morphine, controlled-release [CR] oxycodone, transdermal fentanyl, and methadone); the control drugs were either anticonvulsants indicated for chronic pain (such as gabapentin and pregabalin) or low-dose cyclic antidepressants (such as amitriptyline and desipramine).

For their analysis, the researchers compared 22,912 long-acting opioid episodes with an equal number of control medication episodes. They found that patients prescribed therapy for a long-acting opioid had a risk of all-cause mortality that was 1.64 times greater than that for matched patients starting an analgesic anticonvulsant or a low-dose cyclic antidepressant, corresponding to 69 excess deaths per 10,000 person-years of therapy. 

“[O]f the estimated 69 excess deaths per 10,000 person-years of follow-up among long-acting opioid patients, 47 had an underlying cause of death other than unintentional overdose, and 29 had a cardiovascular cause of death,” the authors wrote, adding that the increased risk of cardiovascular death may be related to the adverse respiratory effects of opioids. However, once patients in the long-acting opioid group had more than 180 days of therapy, their risk of death did not differ significantly from that of the control group.

“The study finding that prescription of long-acting opioids was associated with increased cardiovascular and other non-overdose mortality adds to the already considerable known harms of the opioids and thus should be considered when assessing the benefits and harms of medications for chronic pain,” the authors concluded.

For related information, see the Psychiatric News article “AMA Survey Indicates M.D. Support for Measures to Address Opioid Epidemic.” For guidance on prescribing opioids, see information posted on the website of “Choosing Wisely,” a campaign in which APA is a member. Click here and search on “opioid.”

(Image: Paul Matthew Photography/Shutterstock)