University of Washington Medicine researchers have developed a breakthrough treatment protocol for opioid-use disorder that eliminates the need for patients to undergo withdrawal before starting buprenorphine therapy. The novel approach, published in JAMA Network Open, represents a significant advancement in addressing treatment barriers in the fentanyl era.
The study, conducted in collaboration with Seattle's Downtown Emergency Service Center, enrolled 95 patients struggling with opioid-use disorder and administered injectable-only overlapping buprenorphine without requiring fentanyl cessation. Results demonstrated substantial improvements over traditional methods, with 75% of participants completing the three-day injection series and 64% returning for a second monthly dose.
Addressing Critical Treatment Barriers
Traditional buprenorphine protocols require patients to stop using fentanyl and experience withdrawal symptoms before beginning treatment, creating a significant barrier to care initiation. The new protocol removes this obstacle by allowing patients to continue fentanyl use while beginning buprenorphine therapy through a sequence of long-acting injections administered under the skin.
"Fentanyl has complicated things, making starting buprenorphine trickier, which led our team to look for potentially easier ways to start this lifesaving medication," said Dr. Richard Waters, clinical instructor of family medicine at the University of Washington School of Medicine and medical director of the Downtown Emergency Service Center.
Focus on Vulnerable Populations
The research was conducted within the center's Opioid Treatment Network, which delivers care both in clinical settings and in the field by meeting patients in shelters, supportive-housing buildings, and encampments. Nearly 80% of study participants were experiencing homelessness or living in permanent supportive housing, underscoring the protocol's relevance for highly vulnerable populations.
"Being able to get someone started on life-saving medication like buprenorphine without the need for an initial period of withdrawal is particularly important for people experiencing homelessness," said Dr. Jared Klein, associate professor of medicine in the Division of General Internal Medicine at the University of Washington School of Medicine and senior author of the study.
Integrated Care Model Success
The study demonstrates the effectiveness of integrated care approaches that link treatment to housing and outreach services. Daniel Malone, executive director of the Downtown Emergency Medical Center, emphasized that medication alone is insufficient for optimal outcomes.
"People are more likely to succeed when they have housing, behavioral healthcare, and other robust supports in place," Malone said. "This study shows how integrated care models — linking treatment to housing and outreach — can help people overcome barriers to starting and staying on lifesaving medication."
Clinical Significance and Future Implications
Dr. Waters noted that buprenorphine, along with methadone, represents an essential element of treatment plans for opioid-use disorder. The new protocol's success suggests it may serve as a promising alternative for patients who have struggled to initiate buprenorphine through conventional methods.
"Our results suggest that this method — using a sequence of long-acting buprenorphine injections that go under the skin — may be a promising alternative for people who have struggled to start buprenorphine in other ways," Waters added.
The research represents what Klein described as "a significant contribution to the existing literature around novel methods of starting buprenorphine in the era of fentanyl." The study was conducted from September 2024 to January 2025, with clinical data collected as part of routine operations funded by King County government, the Washington State Health Care Authority, State Opioid Response grants, and the Pacific Hospital Preservation and Development Authority of King County.
