Removing arbitrary limitations on buprenorphine for opioid use disorder

Abstract

The opioid crisis has sharply evolved over the past two decades, shifting first from prescription opioids to heroin and now to fentanyl and other synthetic opioids far more potent than their predecessors. Buprenorphine, a partial opioid agonist, has long been a cornerstone of opioid use disorder (OUD) treatment, demonstrating significant reductions in morbidity and mortality when prescribed appropriately. However, legacy dosing recommendations from an era preceding fentanyl's dominance have resulted in restrictive state and insurance policies that limit patient access to clinically necessary dosages. In the United States (US), recent US Food and Drug Administration (FDA) updates seek to mitigate this issue [1], but broader structural and international policy shifts are needed to align buprenorphine treatment with the contemporary realities of opioid pharmacology and patient need.

The US FDA initially approved buprenorphine-based medications for OUD treatment in 2002, establishing a recommended target dose of 16 mg per day, with 24 mg per day cited as the upper limit beyond which no additional clinical benefit was believed to occur. These recommendations were based on studies conducted in the pre-fentanyl landscape. Today, fentanyl's high potency, low street price per morphine milligram equivalent (MME), and long half-life complicate withdrawal management, often necessitating higher doses of buprenorphine to suppress cravings and stabilize patients effectively [2]. The growing body of evidence supporting higher doses has not yet translated into widespread policy reform. Instead, outdated dosage limits have been used by US states and insurers to justify restrictive prescribing practices that hinder effective treatment [3].

Local policies on buprenorphine dosing vary considerably, often in ways that can undermine patient care [4]. Some US states, such as Kentucky, impose arbitrary dosage caps, while others, such as Tennessee and West Virginia, enforce dosage restrictions with cumbersome exceptions, such as chart documentation or required referral to an addiction specialist. Additional bureaucratic barriers—such as prior authorizations or excessive documentation requirements—further delay or prevent treatment escalation, disproportionately affecting Medicaid beneficiaries and uninsured individuals [5].

Additionally, insurance coverage for extended-release injectable buprenorphine (Sublocade), presents another significant hurdle. Originally approved for monthly administration, new data suggest that an accelerated induction phase—including a second 300 mg dose as early as day 8—may improve stabilization outcomes. Insurance coverage has not kept pace with these findings, leaving patients with inadequate options for stabilization and relapse prevention [6]. Although barriers such as quantity limits and prior authorization are in place to ensure appropriate medication use [7], the reality of the opioid epidemic is that the treatment landscape changes quickly. The standard of care may not have large-scale, randomized controlled trials. Instead, to pivot and save lives, effective OUD management must rely on expert opinion, a practice broadly applied in medical guideline development to address evidence gaps in published literature [8]. This poses obvious challenges for public and private insurers.

In response to growing clinician and patient advocacy, the FDA revised its buprenorphine labeling on 27 December 2024, clarifying that higher doses may be necessary and discouraging the use of prior dosing language as a justification for denial of care [1]. Although this update is a valuable step, it remains to be seen whether states and insurers will swiftly adapt their policies. Historical precedent suggests that regulatory inertia may delay meaningful change unless additional pressure is applied through litigation, policy advocacy, and professional guideline updates.

The issue of restrictive dosing is not unique to the United States. Across the world, there is growing recognition of the need for individualized dosing strategies. Canada, Australia and other countries have begun adapting OUD treatment strategies in response to fentanyl, allowing for flexible dosing and rapid induction protocols. One study on methadone found that some patients required doses significantly higher than traditional suggested guidelines to achieve optimal outcomes [9]. Emerging data from Canada indicate that higher-dose buprenorphine can improve retention and reduce illicit opioid use among fentanyl-exposed individuals [10]. Furthermore, European nations with established heroin-assisted treatment programs provide an alternative framework for managing patients with severe OUD who may not stabilize on standard buprenorphine regimens [11]. British Columbia's guidelines for clinical management of OUD acknowledge that the daily maximum dose cited in the Suboxone Product Monograph preceded the fentanyl era, and that more recent data supports a daily dose up to 32 mg [12]. The British Advisory Council on the Misuse of Drugs acknowledges ‘good evidence that high doses of methadone and buprenorphine result in less opiate use and in a reduction in risk behaviors.’ [13].

Harold A. Pollack: Conceptualization (equal); funding acquisition (lead); writing—original draft (equal); writing—review and editing (equal). Nicole Gastala: Conceptualization (equal); writing—original draft (equal); writing—review and editing (equal). Brianna Hudak: Conceptualization (equal); writing—original draft (equal); writing—review and editing (equal). Mai T. Pho: Conceptualization (equal); writing—review and editing (equal). Katharine Wilcox: Conceptualization (equal); writing—original draft (equal); writing—review and editing (equal).

Funding for this editorial is provided by the National Institute on Drug Abuse (NIDA). Any opinions expressed are those of the authors, and do not represent those of NIDA or any employer or organization.