Extended-Release Buprenorphine Shows Superior Retention for Fentanyl Users, New Study Finds

The fentanyl era has fundamentally altered the landscape of opioid addiction treatment, forcing clinicians to reconsider protocols developed for heroin and prescription opioid dependence. New real-world evidence presented at the American Society of Clinical Psychopharmacology (ASCP) Annual Meeting suggests that extended-release injectable buprenorphine may offer decisive advantages over traditional daily formulations for patients using fentanyl—a finding with significant implications for how medication-assisted treatment is delivered amid the deadliest phase of the overdose crisis.

Braeburn Inc. presented three studies analyzing outcomes for patients treated with BRIXADI, a weekly and monthly extended-release buprenorphine injection approved by the FDA in 2023. The most clinically significant finding came from a retrospective cohort study comparing treatment retention among patients with recent fentanyl use who received either extended-release injectable buprenorphine or sublingual formulations through a national network of outpatient addiction clinics.

The Fentanyl Challenge

Fentanyl's pharmacological properties have complicated traditional buprenorphine induction protocols. The synthetic opioid's high potency and lipophilicity result in prolonged withdrawal syndromes that can last days rather than hours, making the transition from full agonists to partial agonists particularly challenging. Patients often experience precipitated withdrawal—severe symptoms triggered when buprenorphine displaces fentanyl from opioid receptors—creating barriers to treatment initiation and early retention.

The study data suggests that once patients successfully initiate treatment, extended-release formulations may provide better protection against relapse. Researchers found that patients treated with BRIXADI demonstrated greater retention on buprenorphine over six months compared to those receiving sublingual buprenorphine, with the difference achieving statistical significance.

Mechanisms of Improved Retention

Dr. Joshua M. Cohen, Chief Medical Officer at Braeburn, emphasized that the findings reflect evolving clinical realities. "For too long, treatment decisions have been shaped by older research that may not reflect the full picture of how buprenorphine works, particularly as the opioid crisis has evolved with the rise of high-potency synthetic opioids," he noted in the presentation.

Several mechanisms may explain the superior retention observed with extended-release formulations. The steady plasma concentrations maintained by weekly or monthly injections eliminate the peaks and troughs associated with daily dosing, potentially reducing craving fluctuations that trigger relapse. Additionally, the removal of daily medication rituals—opening bottles, placing films under the tongue, managing take-home supplies—reduces opportunities for diversion and the psychological associations that can reinforce addictive patterns.

Perhaps most importantly for fentanyl users, the extended-release formulation ensures continuous receptor occupancy. This pharmacological "floor" may be particularly protective against the extreme potency of fentanyl, which can overwhelm partial agonist blockade when buprenorphine levels fluctuate.

Real-World Utilization Patterns

A second analysis of specialty pharmacy data involving over 30,000 patients revealed how clinicians are actually using extended-release buprenorphine in practice. The data showed substantial dose variation across the patient population, with all available doses of both weekly and monthly formulations being utilized.

For BRIXADI Weekly, 36.1% of dispensed units were the 24 mg dose, followed by 29.6% at the maximum 32 mg strength. Among monthly formulations, the highest dose (128 mg) accounted for 44.4% of units, suggesting that many patients require substantial buprenorphine exposure to achieve therapeutic effects—particularly relevant given fentanyl's potency.

Notably, 29.6% of patients changed doses over the course of treatment, and 60.8% of those starting on weekly injections eventually transitioned to monthly formulations. This pattern suggests that extended-release buprenorphine treatment involves dynamic dose optimization rather than fixed protocols, with patients benefiting from individualized adjustments as their clinical needs evolve.

Withdrawal Suppression at Lower Concentrations

A third presentation examined the relationship between buprenorphine plasma concentrations and withdrawal suppression, offering insights into dosing strategies. Post-hoc analysis of 110 participants found that both weekly (32 mg) and monthly (128 mg) formulations effectively suppressed opioid withdrawal throughout their dosing intervals—including in patients with lower plasma concentrations than previously assumed necessary.

This finding challenges conventional wisdom about buprenorphine dosing and suggests that some patients may achieve adequate withdrawal suppression at lower exposure levels than typically targeted. The implications extend beyond individual treatment decisions to broader questions about access and cost, as higher-dose formulations carry greater expense and may be subject to more restrictive insurance authorization.

Clinical and Policy Implications

The convergence of fentanyl's dominance in the illicit drug supply and the availability of extended-release buprenorphine formulations represents a potential inflection point in addiction treatment. While sublingual buprenorphine has dramatically expanded access since the X-waiver elimination in 2023, the new data suggests that formulation choice may meaningfully impact outcomes for the patient population most at risk of overdose death.

However, barriers to extended-release adoption remain substantial. BRIXADI requires administration by healthcare providers, necessitating clinic visits that may be challenging for patients with transportation limitations or inflexible work schedules. The REMS (Risk Evaluation and Mitigation Strategy) program restricts dispensing to certified providers and pharmacies, creating access bottlenecks in underserved areas. And cost—often exceeding $1,000 per monthly injection—presents formidable obstacles for uninsured patients and those with high-deductible plans.

The Broader Context

These findings arrive amid encouraging but fragile progress in the overdose crisis. CDC data released this month shows drug overdose deaths declined approximately 14% in 2025 to roughly 70,000 fatalities—the third consecutive year of improvement. Yet fentanyl continues to drive mortality, and emerging threats including xylazine and medetomidine are complicating emergency response.

The research underscores a fundamental principle increasingly recognized in addiction medicine: medication adherence—not just prescription—determines outcomes. Extended-release formulations address adherence through their delivery mechanism rather than patient behavior, potentially offering more reliable protection for populations struggling with the chaos that often accompanies active addiction.

As the field continues adapting to fentanyl's pharmacological realities, these data suggest that treatment protocols may need to evolve beyond one-size-fits-all approaches. For patients using high-potency synthetic opioids, extended-release buprenorphine appears to offer measurable advantages in sustaining recovery—a finding that should inform both clinical practice and coverage policy as the nation continues its long struggle against overdose mortality.