Opioid dose escalation, rapid tapering associated with all-cause mortality in older patients
Overdose and opioid use disorder risk were reduced in patients who underwent rapid tapering of long-term opioid therapy for chronic noncancer pain, but their risk of all-cause mortality was higher than patients who stayed on a steady dose.
Rapid changes in dose for patients on long-term opioid therapy (LTOT) for chronic noncancer pain may negatively affect all-cause mortality, a study found.
To examine the relationships between opioid tapering and subsequent overdoses, opioid use disorder (OUD) diagnoses, and all-cause mortality, researchers conducted a nested case-control study among Medicare beneficiaries ages 65 years and older with chronic noncancer pain treated with LTOT from 2012 to 2020. Researchers assessed opioid tapering as a monthly dose change percentage with four levels: steady dose (±10% dose change), slow tapering (10% to 40% dose reduction), rapid tapering (>40% dose reduction), and dose escalation (>10% dose increase). Results were published April 22 in the Journal of General Internal Medicine.
Among a cohort of 82,295 patients, there were 1,333 overdoses, 4,933 cases of OUD, and 5,971 deaths. After the researchers controlled for all covariates, compared with steady dose, the odds of overdose were significantly lower with rapid tapering (adjusted odds ratio [OR], 0.74; 95% CI, 0.55 to 0.99) and significantly higher with dose escalation (aOR, 2.08; 95% CI, 1.64 to 2.65). Similarly, the odds of OUD were significantly lower for rapid tapering (aOR, 0.53; 95% CI, 0.46 to 0.60) and significantly higher for dose escalation (aOR, 1.60; 95% CI, 1.42 to 1.81). Compared to steady dose, odds for all-cause mortality were higher among patients undergoing rapid tapering (aOR, 1.28; 95% CI, 1.14 to 1.44) or dose escalation (aOR, 1.51; 95% CI, 1.34 to 1.71).
Compared with a steady opioid dose, slow tapering was not significantly associated with increases in the study outcomes.
The study authors said that clinicians should regularly assess patients on LTOT, considering the benefits and risks of treatment that incorporate evolving evidence on dose changes. Aging affects patients' ability to metabolize drugs, and older patients are also more likely to have multiple comorbidities and need multiple medications, making managing those on LTOT a challenge. The benefits and risks of both LTOT and tapering should be carefully evaluated before initiating dose changes, the study authors said.
“Overall, slow opioid tapering is relatively safe and can be a viable approach to gradually reduce opioid doses, especially in patients where benefits of LTOT do not outweigh risks,” they wrote. “In these situations, clinicians should work with patients to closely monitor any signs of adverse events. Rapid tapering should not be recommended as a tapering strategy as it is associated with significantly increased risks of mortality.”