The growing use of fentanyl challenges current methadone induction protocols

A growing number of physician assistants and nurse practitioners (NPs) are working in the field of addiction medicine, including opioid treatment programs (OTPs) where they are increasingly able to practice in a more autonomous. A comment recently published in the Drug Treatment Journal highlights the challenges OTP practitioners face in reaching therapeutic doses of methadone for patients who use fentanyl instead of heroin.1 The reviewers noted that with “the increased potency of fentanyl relative to other opioids, many articles have described the need for higher doses of methadone to achieve the therapeutic goal of reducing and suppressing drug withdrawal. opioids and the subsequent illicit use of fentanyl”.

The commentators make several key observations and related recommendations. One of the key findings is that fentanyl-using patients who enter OTPs may view the increased time it takes to get an effective dose of methadone as evidence that methadone treatment will not work for them, and that this can be another barrier to treatment.

Running guidelines for methadone treatment by the Substance Abuse and Mental Health Services Administration (SAMHSA) recommend a maximum starting dose of 30 mg per federal OTP regulationsthat were established before synthetic opioids became the first cause of opioid-related death in the United States. The guidelines state that the dose can be increased by 5 mg to 10 mg every 3 to 5 days. This dosing regimen may be ineffective for patients using fentanyl given their higher tolerance; it may take up to a month or more to reach an effective dose of methadone in these patients.

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The commentators offer several points to consider when adapting induction protocols to meet the therapeutic needs of patients using fentanyl and noted that change can be achieved without lengthy regulatory reform. The authors offer evidence from several US studies in which a plus fast the methadone induction regimen allowed faster reaching of therapeutic doses without increasing the risk of overdose, which is the highest risk during the first few weeks of methadone induction in OTP settings.

This evidence indicates that PTA providers attempt to address these concerns with a variety of induction variations, suggesting that more patient-focused research using fentanyl is needed.

This comment is valuable in attempting to stimulate new, innovative efforts to adapt the OTP model of methadone to meet the challenges posed by the increased potency of fentanyl. Commitment to early induction can be difficult for any patient with an opioid use disorder who is seeking treatment. Even before the rise in fentanyl use, many patients with opioid use disorder struggled with the induction period when initiated at doses that did little to the beginning to suppress withdrawal symptoms, which are common. This problem is even greater now with the increase in the use of fentanyl, and this commentary demonstrates the need for OTPs to offer a model for how OTPs and OTP regulators can design induction protocols more effective that are both safe and effective.


Buresh M, Nahvi S, Steiger S, Weinstein ZM. Adapting methadone inductions to the age of fentanyl. J Subst Abuse Treat. 2022;141:108832. doi:10.1016/j.jsat.2022.108832

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