Out-of-Hospital Mortality Among Patients Receiving Methadone for Noncancer Pain

Prescription of Long-Acting Opioids and Mortality in Patients With Chronic Noncancer Pain

“…Thus, of the estimated 69 excess deaths per 10,000 person years of followup 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 increased risk for cardiovascular death persisted when patients prescribed methadone, a known pro-arrhythmic drug, 16 were excluded from the cohort.…”

“…16 The analysis made the conservative assumption that control medication deaths were not misclassified.…”

“…Second, what was the relative risk for deaths outside of the hospital, which are less likely to be due to existing conditions and most plausibly related to opioid adverse effects? 16 Third, were there differences in the risk of deaths other than those from unintentional medication overdose?…”

CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016

“…A fair-quality retrospective cohort study based on national Veterans Health Administration system pharmacy data found that methadone was associated with lower overall risk for all-cause mortality versus morphine (81), and a fair-quality retrospective cohort study based on Oregon Medicaid data found no statistically significant differences between methadone and long-acting morphine in risk for death or overdose symptoms (82). However, a new observational study (83) found methadone associated with increased risk for overdose versus sustainedrelease morphine among Tennessee Medicaid patients. The observed inconsistency in study findings suggests that risks of methadone might vary in different settings as a function of different monitoring and management protocols, though more research is needed to understand factors associated with safer methadone prescribing.…”

Pain in the Frail or Elderly Patient: Does Tapentadol Have a Role?

“…With the exception of buprenorphine, opioids generally require dosage adjustment in age-related renal impairment [20]. Methadone has highly variable pharmacokinetics [41]; in addition, even doses of 20 mg a day or less have been associated with an increased risk of death compared with an equivalent morphine dose [42], and thus other opioids should be used preferentially. Tramadol has a different mode of action to other opioids as it also prevents the neuronal re-uptake of serotonin.…”