Fentanyl Exposure Not Associated With Perceived Adequacy of Methadone Dose

Some experts postulate that higher therapeutic doses of methadone may be needed to treat opioid use disorder among people exposed to fentanyl, due to fentanyl’s high potency. Researchers used data from three observational cohorts of people who use drugs in Vancouver, Canada to investigate the association between fentanyl-positive urine drug tests (UDT) and patients feeling that their methadone dose is inadequate. UDT results were categorized as: “fentanyl-positive” (with or without other opioids); “fentanyl-negative, non-fentanyl opioid-positive”; or “negative” (no opioid other than methadone detected).

• There were 1732 encounters among 616 participants who had a UDT and reported being prescribed methadone (≥60 mg); 53 percent of encounters had a fentanyl-positive UDT, 10 percent were fentanyl-negative, opioid-positive, and 37 percent were negative.
• Participants reported feeling that their methadone dose was inadequate in 18 percent of encounters.
• Those who perceived receiving an inadequate methadone dose were younger, and more likely to have experienced homelessness, or to report daily use of non-prescribed opioids or stimulants; their methadone dose was not significantly lower compared with the rest of the cohort (median for all was 100 mg).
• In adjusted analyses, compared with encounters with a fentanyl-positive UDT, encounters with fentanyl-negative, opioid-positive results were not associated with reports of inadequate methadone dose, but encounters with negative results were associated with lower odds of reporting inadequate methadone dose (adjusted odds ratio, 0.59).

Comments: This study supports guidelines recommending patient-centered methadone dose titration in response to ongoing cravings and opioid use. It suggests that we should not assume that people who are exposed to fentanyl will need higher doses.

Darius A. Rastegar, MD

Reference: Young S, Raboud J, Dodd Z, et al. Examining the association between fentanyl use and perceived adequacy of methadone dose: a retrospective cohort study. Drug Alcohol Depend. 2025;267:112547.