In a significant setback for opioid addiction treatment strategies, researchers at UC San Francisco have found that the increasingly popular low-dose initiation approach for buprenorphine treatment shows limited effectiveness in patients using fentanyl. The study, published in JAMA Network Open on January 24, revealed that only 34% of participants successfully achieved optimal buprenorphine dosing using this microdosing method.
The research, representing the largest evaluation of low-dose buprenorphine initiation to date, included 126 participants treated at two San Francisco outpatient substance-use disorder clinics between May 2021 and November 2022. The study emerged from urgent efforts during the COVID-19 pandemic to address surging fentanyl overdoses.
Treatment Protocols and Outcomes
Participants were offered two protocol options: a four-day treatment regimen with four daily doses or a seven-day approach with two to three daily doses. To ensure accurate dosing, medications were provided in bubble packs. The four-day protocol showed marginally better results, with a 38% success rate compared to 28% for the seven-day approach. Notably, only 22% of participants maintained the treatment for at least 28 days.
"This doesn't seem like it's working the way we had hoped," stated Dr. Leslie W. Suen, lead author and assistant professor at the UCSF Division of General Internal Medicine. "But when people expect it to work, and it doesn't work for them, they feel like there's something wrong with them."
The Fentanyl Challenge
The treatment complications stem from fentanyl's unique pharmacological properties. Unlike heroin and other opioids that leave the body predictably, fentanyl stores longer in fat cells, making it difficult to predict clearing times. This characteristic has complicated traditional buprenorphine initiation methods, which typically require patients to stop opioid use and experience withdrawal before starting treatment.
Clinical Implications
Buprenorphine, a partial opioid agonist, remains the most widely used medication among the three FDA-approved treatments for opioid use disorder. The other options include methadone, administered through certified treatment clinics, and injectable naltrexone for patients who have already achieved opioid independence.
The study's findings highlight persistent challenges in addiction treatment, including limited physician training in prescribing buprenorphine, insurance barriers, and ongoing stigma. Researchers are now conducting follow-up studies to understand why this promising approach fell short of expectations and to develop more effective treatment strategies for fentanyl users seeking recovery.
