1. Long-term opioid therapy for chronic non-cancer pain is associated with an increase in all-cause mortality.
2. Increased mortality was due to greater instances of unintended overdoses and cardiovascular mortality.
Evidence Rating Level: 2 (Good)
Study Rundown: The use of opioids for management of chronic pain has skyrocketed over the past 2 decades. Likewise, the number of hospitalizations and deaths due to opioid overdose has dramatically increased. Meanwhile, alternative medications may be better suited to addressing chronic pain. Therefore, this study compared the risk of death in patients starting long-term opioid therapy or a control therapy including analgesic anticonvulsants or low-dose tricyclic antidepressants. In a retrospective analysis, 45 824 patients with chronic, non-cancer pain were prescribed either an opioid or a control medication. At the end of follow-up, a significant association between long-term opioid use and all-cause mortality was identified. This mortality was due in large part to a significant increase in unintentional overdoses although excess cardiovascular mortality was also observed. The greatest increase in mortality occurred within 30 days of starting the pain medication. Although these results are from a retrospective study and cannot prove causation, they highlight the myriad adverse effects of opioid analgesics when given for chronic, non-cancer pain.
In-Depth [retrospective cohort]: This retrospective cohort study assessed 45 824 Tennessee Medicaid enrollees who were started on an analgesic therapy for chronic, non-cancer pain between 1999 and 2012. A total of 22 912 patients started on an opioid were matched, using propensity scoring, with an equal number of similar patients started on an anticonvulsant or tricyclic antidepressant for pain relief. All patients were followed for 30 days after their last refill of prescribed analgesic.
Participants prescribed opioids had a higher incidence of all-cause mortality than their matched counterparts (167.1 deaths per 10,000 person-years among patients prescribed opioids vs. 107.0 per 10,000 patient-years among those prescribed control medications; HR 1.64, 95%CI 1.26–2.12). This excess mortality was due in large part to unintentional overdoses (HR 3.37, 95%CI 1.47–7.7), although there was also a significant increase in cardiovascular causes of death (HR 1.65; 95%CI 1.1–2.46). Results were stabile to a sensitivity analysis. The greatest increase in the risk of death was found within the first 30 days of starting analgesic therapy (HR 4.16; 95%CI 2.27–7.63).
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