Examining the association between fentanyl use and perceived adequacy of methadone dose: A retrospective cohort study

People exposed to fentanyl may report that the dose of methadone in the commonly accepted therapeutic range feels too low. We examined self-reported methadone dose adequacy.

We conducted a retrospective cohort study of individuals prescribed methadone at a dose of at least 60mg daily using data from three community-recruited prospective cohort studies of people who use drugs in Vancouver, Canada from December 2016 through March 2020. We used multivariable generalized estimating equations to estimate the relationship between type of opioid exposure - measured using urine drug tests and categorized as: (1) fentanyl-positive, (2) fentanyl-negative opioid-positive, and (3) fentanyl- and opioid-negative, and report of their methadone dose being too low.

In total, 1732 observations from 616 participants were included, of which 914 (52.8 %) observations had a fentanyl-positive, 178 (10.3 %) had a fentanyl-negative opioid-positive, and 640 (37.0 %) had a fentanyl- and opioid-negative urine drug test. Compared with those with a fentanyl-positive urine drug test, in the adjusted model those with a fentanyl- and opioid-negative urine drug test were significantly less likely to report their methadone dose as too low (adjusted odds ratio [AOR]=0.57, 95 % CI 0.41-0.81), while there was no significant association among those with a fentanyl-negative opioid-positive urine drug test (AOR=0.92, 95 % CI 0.59-1.43).

We found that exposure to non-fentanyl opioids while on methadone was not associated with feeling the dose was too low compared with individuals exposed to fentanyl. Our findings support adequate titration of methadone for individuals with continued exposure to unregulated opioids including fentanyl.