Fentanyl is changing how doctors treat opioid use disorder

HERSHEY, Pa. — For years, buprenorphine — one of the primary medications used to treat opioid use disorder — has been a critical bridge to recovery, helping to reduce illicit drug use and overdose deaths. But with the changing landscape of the illicit drug market, particularly the rise of the potent synthetic opioid fentanyl, health care providers have found that traditional treatment protocols aren’t as effective as they used to be.

A new national survey, led by researchers at the Penn State College of Medicine and the University of Pittsburgh, found that nearly three-quarters of clinicians encountered significant obstacles when starting buprenorphine treatment for patients using fentanyl. More than 67% have modified their treatment protocols, such as adjusting dosages.

But this is more than a technical hurdle for health care providers, the researchers said. It’s a major barrier for people seeking treatment for opioid use disorder who experience rapid withdrawal symptoms or prolonged symptoms as a result. The study, published in JAMA Open Network, highlights the complexity of treating opioid use disorder.

“It’s a public health crisis. Buprenorphine is a lifesaving option due to its safety profile and ease of access,” said lead author Sarah Kawasaki, associate professor of psychiatry and behavioral health and of medicine at Penn State College of Medicine. “We need more research and updated clinical guidelines for the fentanyl era.”

Treatment for opioid use disorder used to be predictable, Kawasaki said. Most people were using heroin, which could be verified on drug screenings. Clinicians could then give buprenorphine reliably at certain dosages and time intervals. Patients could access the medication at pharmacies and would do well.

Kawasaki said things started to change around 2017. More patients were testing positive for fentanyl. Unlike older opioids, fentanyl’s unique chemistry — specifically its ability to "hide" in the body's fat cells — makes the transition to buprenorphine more difficult. People experienced withdrawal symptoms for much longer than typical or had withdrawal symptoms so intense that they reported feeling allergic to the medication.

“Someone can get really sick or get tired of the whole process that they stop treatment. They might start using again and might overdose or die,” Kawasaki said.

Patients also began requesting methadone, another standard protocol for managing opioid use disorder. However, methadone is only available from an estimated 2,000 licensed facilities in the United States, Kawasaki said, compared to more than 70,000 pharmacies where patients can access buprenorphine.

To understand how doctors were responding to the challenges of starting patients on buprenorphine in the rapidly changing illicit drug market, the researchers surveyed 396 health care providers. The pool of participants was a nationally representative sample of physicians and advanced practice clinicians who initiated at least 10 patients with opioid use disorder onto buprenorphine during the prior year and at least one patient in the past 90 days.

The researchers found that:

• 72% of respondents reported experiencing challenges starting buprenorphine treatment among patients using fentanyl in the past year
• Nearly 62% of respondents reported one or more instances in which the patient experienced a severe and sudden onset of withdrawal symptoms
• 52.8% reported cases of prolonged withdrawal where symptoms lasted days instead of hours
• Those who worked in high-volume outpatient settings were more likely to report these challenges.

Approximately 67% reported modifying their standard protocols. In some cases, providers used doses that were much smaller than previously recommended while others used much higher doses. Some clinicians prescribed adjunct medications to help with withdrawal symptoms. Still others referred patients to inpatient treatment or to methadone because of the challenges of initiating buprenorphine treatment.

Despite these challenges, the researchers emphasized that buprenorphine remains a life-saving treatment for those with opioid use disorder and that many patients do not encounter problems when starting buprenorphine. According to Kawasaki, the study highlighted the need to develop evidence-based guidelines to successful initiate buprenorphine in light of more potent drugs.

“Buprenorphine still works. If you or a loved one needs help, don’t be afraid to reach out,” Kawasaki said.

Erin Winstanley, professor of medicine at the University of Pittsburgh, is senior author of the study. Other authors on the study from the University of Pittsburgh include Jane Liebschutz, professor of medicine; Cristina Murray-Krezan, associate professor of medicine; Galen Switzer, professor of medicine; Samantha Nash, clinical research coordinator; and Kwonho Jeong, biostatistician.

Funding from the National Institute on Drug Abuse supported this work.

At Penn State, researchers are solving real problems that impact the health, safety and quality of life of people across the commonwealth, the nation and around the world.

For decades, federal support for research has fueled innovation that makes our country safer, our industries more competitive and our economy stronger. Recent federal funding cuts threaten this progress.

Learn more about the implications of federal funding cuts to our future at Research or Regress.