AIMS: Patients in methadone medication treatment for opioid use disorder (M-MOUD) typically have a complex history of opioid use, often in combination with other drugs. It is unknown how frequently M-MOUD patients experience persistent substance or polysubstance use. We measured trends in illicit substance use in a large, multistate population of M-MOUD patients and persistence of substance use in the first year of treatment.

DESIGN: Retrospective cohort study of United States (US) M-MOUD patients from 2017 to 2021, focused on urine drug specimens provided for testing to Millennium Health, a third-party laboratory. Specimens were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Generalized estimating equations (GEE) were used to estimate the average trends in positivity during time in treatment. Specimens were obtained from clinics in 10 US states that provided at least 300 unique patients during the study period. Participants were patients with opioid use disorder receiving M-MOUD (n = 16 386).

MEASUREMENTS: Positivity rates for heroin, fentanyl, methamphetamine and cocaine.

FINDINGS: From 2017 to 2021, yearly crude positivity rates for first collected specimens increased for fentanyl, methamphetamine and cocaine; for heroin positivity did not significantly change. In regression models estimating patient trajectories from week 1 to week 52, marginal fentanyl positivity declined from 21.8% to 17.1% and heroin positivity declined from 8.4% to 4.3%, but positivity for methamphetamine and cocaine did not significantly change, remaining at an average of 17.7% and 9.2%, respectively.

CONCLUSIONS: Between 2017 and 2021, United States patients presenting to opioid treatment programs increasingly tested positive for fentanyl, methamphetamine and cocaine. Methadone medication treatment for opioid use disorder appears to remain an effective intervention for reducing illicit opioid use.