Fentanyl and other high-potency synthetic opioids are changing how doctors initiate medications for opioid use

Fentanyl and other high-potency synthetic opioids (HPSOs) are the leading cause of opioid overdose deaths in the United States. These substances have changed the way that hospitals start medication to treat opioid use disorder (OUD), but no standards exist.

A new study published in JAMA Network Open on August 7, 2025, assessed new initiation approaches used by hospital-based addiction consult services (ACS) to treat OUD around the country.

FDA-approved medications, including methadone and buprenorphine, have been demonstrated to reduce opioid-related mortality and overdoses by as much as 50%. Yet, clinical guidelines on how to initiate these lifesaving medications—which were developed when heroin and prescription opioids dominated the unregulated opioid supply—are outdated.

Researchers surveyed 58 directors of hospital-based ACS and found that most ACS recognized the prevalence of HPSOs, and agreed they have changed how they approach medication initiation.

“Our study shows hospital-based addiction consult clinicians are adapting their care to a rapidly evolving drug supply to best serve the people they’re caring for. As the drug supply continues to evolve so quickly, these practice changes are outpacing clinical guidelines and available research,” says Shawn Cohen, MD, assistant professor of medicine (general medicine) and lead author of the study.

Individuals using HPSOs who are provided the same methadone initiation approach as those using heroin or prescription opioids may still experience opioid withdrawal symptoms.

“Inadequately treated opioid withdrawal causes unnecessary patient discomfort and can often lead to poor treatment outcomes for people with OUD,” says Melissa Weimer, DO, MCR, associate professor of medicine (general medicine) and of epidemiology (chronic diseases) at Yale School of Public Health (YSPH), medical director of the Yale Addiction Medicine Consult Service (YAMCS) at Yale New Haven Hospital (YNHH), and co-author of the study.

New treatment approaches include more rapid methadone initiation, as well as both high- and low-dose buprenorphine initiation protocols. Hospital-based ACS have emerged on the frontier of this new treatment landscape.

“EDs and hospitals are on the front lines of the overdose crisis and see some of the most unfortunate complications of opioid use. Hospital-based addiction services like the one at Yale New Haven Hospital can deploy innovative specialty care to patients’ bedsides because of close monitoring in the hospital environment, regulatory allowances, and close collaboration with pharmacists and other hospital-based specialists,” says Weimer.

In addition to further study of the safety and effectiveness of novel medication initiation approaches, the authors call for the incorporation of community-partnered research methods to inform thoughtful and time-sensitive guidelines development in collaboration with individuals and communities impacted by OUD and with the changing opioid supply in mind.

“The people most impacted by changes in the drug supply, and those with the most insight into how we can adapt and improve our care, are people who use drugs. For clinicians and researchers to be able to improve care as rapidly as the drug supply changes, research and clinical care need to embrace a community-partnered approach,” Cohen says.