A decade ago. fentanyl, the white powder that closely resembles heroin, hit the illicit drug scene, and it was a drug dealer’s dream—highly potent, yet cheap.
But illicit fentanyl proved risky. Because fentanyl is 50 to 100 times more potent than morphine, many who used it died. Others feared fentanyl at first, but quickly grew to appreciate its extra zing—then couldn’t get enough of it. Some turned to smoking it, to minimize risk. But fentanyl deaths continued to soar.
Experts searched for solutions. More potent, longer-acting opioid antagonists? Higher doses of naloxone?
Neither, according to an article published online a year ago in the International Journal of Drug Policy. Higher doses of naloxone, the authors said, “could have unintended consequences”—severe withdrawal symptoms, leading to a fear of forced fentanyl withdrawal—causing some people using fentanyl to stop carrying naloxone for protection.
Last month, as the debate continued, AT Forum’s contributing writer Alison Knoph summarized an August 7 NBC News story, “Once feared, illicit fentanyl is now a drug of choice for many opioid users.” The NBC story called for higher doses of naloxone to reverse overdoses, and for higher doses of opioid agonists as well. (Methadone is an opioid agonist; naloxone is an opioid antagonist.) Some NBC sources wanted new, more potent, longer-acting opioid antagonists, reasoning that they could join naloxone in counteracting the greater potency of fentanyl. As for testing potent new antagonists by using lower doses, Alison’s medical experts said that could result in damage from lack of oxygen. Higher doses of naloxone could have unintended consequences, they agreed, but at least “these patients are alive and without permanent brain or other damage.” Alison noted that some patients have complained about the severe withdrawal symptoms.
New Approach Zeroes in on OTPs and Methadone Induction
Amid the back and forth on the fentanyl problem, an article published in the Journal of Substance Abuse Treatment presents a new approach. Circumventingthe usual issues, the article zeroes in on methadone induction and the role of opioid treatment programs (OTPs), as seen by OTP and inpatient consult service addiction medicine physicians with expertise in treating opioid use disorders. The authors are affiliated with Johns Hopkins Medical Center, Boston Medical Center, Montefiore Medical Center, and Albert Einstein College of Medicine.
The article calls for OTPs to:
- Develop induction schedules for rapidly administering methadone
- Assign panels of experts to review data gathered from the new schedules
- Use the new data to create updated evidence-based guidance for methadone induction
Some may take issue with the idea of rapid methadone induction, and the authors agree it’s not appropriate for everyone. Standard induction works quite well for some people; others aren’t eligible for rapid induction, due to coexisting conditions—pulmonary disease, cirrhosis, end-stage renal disease, congestive heart failure, or ventricular arrhythmia—or because of relative contraindications listed in the publication.
Authors of the Commentary explain that recent induction-reform efforts in the COVID-19 era have focused on relaxing take-home regulations, and haven’t addressed what the authors believe is the real need—”to adapt methadone induction schedules to be more rapid in the fentanyl era, as allowed by current regulations [emphasis added].”
Current Methadone Induction Guidelines Preceded the Fentanyl Crisis
Current methadone guidelines, created before the days of fentanyl, are conservative and serve two purposes: prevent methadone diversion, and lower the risk of methadone overdose. Those who drafted the guidelines limited the first dose of methadone to 30 mg.
. . . but that’s followed by a key clause: “unless the program physician documents in the patient’s record that 40 milligrams did not suppress opiate abstinence symptoms [emphasis added]…” Any additional dose increases are a matter of OTP discretion.
The key clause provides leeway for physicians to use a higher dose when necessary, while staying within the guidelines. Currently, most methadone titrations are slow, with increases of 5 to 10 mg every 3 to 5 days, but OTPs have regulatory flexibility to increase more rapidly.
The guidelines note that although the overdose risk peaks during the first two weeks of methadone treatment, a key characteristic of fentanyl is a marked increase in opioid tolerance. This means that those using fentanyl may be slow to reach the point where a minimum daily .therapeutic dose of methadone—60 to 120 mg—is effective. In fact, some may not reach an effective dose during the first weeks—or even the first months—of methadone treatment.
“We know that current protocols aren’t working for many patients and we desperately need to adapt,” lead author Megan Buresh, MD, told AT Forum. “The opioid landscape has drastically changed, but most OTPs have not. The beauty is that current regulations don’t restrict methadone dosing after the first day, so this an area where we can make changes now.”
The Commentary authors emphasize the importance of balancing risks—
Risks of Death
|—from methadone toxicity||—from opioid overdose|
|—from ongoing fentanyl use|
|—from methadone discontinuation|
Clearly, the three items on the right tip the scale to higher risks than any risks associated with methadone toxicity. The last example alone—discontinuing methadone—carries a 10-fold increase in the risk of death occurring within four weeks.
Decreasing the Risk of Fentanyl-Related Death
In calling for OTPs to adapt methadone inductions to the fentanyl era, reaching a therapeutic dose more quickly, the authors hope to increase patient engagement and retention in treatment, while decreasing opioid-related mortality.
Others, as well as OTPs, have a responsibility, the authors say: “Without expert guidance from SAMHSA or professional organizations, OTPs may remain in a state of inertia; continue with outdated dosing protocols; and risk patients’ treatment discontinuation, overdose, and death.”
Bottom line: The recommended approach calls on OTPs to play a leading role in easing the fentanyl crisis. If OTPs adapt protocols for methadone induction to provide a therapeutic dose quickly, more people will stay in treatment. And that, the authors believe, is when we can hope to see a drop in fentanyl-related deaths.
Buresh M, Nahvi S, Steiger S, Weinstein ZM. Adapting methadone inductions to the fentanyl era. J Subst Abuse Treat. 2022;141:108832. doi:10.1016/j.jsat.2022.108832.
Hill LG, Zagorski CM, Loera LJ. Increasingly powerful opioid antagonists are not necessary. Int J Drug Policy. 2022;99:103457. doi:10.1016/j.drugpo.2021.103457.
Knopf A. Higher doses of methadone, buprenorphine, and naloxone called for in fentanyl era. Addiction Treatment Forum. August 10, 2022.
Edwards E. One nation overdosed. NBC News. August 7, 2022. https://www.nbcnews.com/health/health-news/feared-illicit-fentanyl-now-drug-choice-many-opioids-users-rcna40418