Buprenorphine Dose and Time to Discontinuation Among Patients With Opioid Use Disorder in the Era of Fentanyl

Abstract

ImportanceBuprenorphine treatment for opioid use disorder (OUD) has more than doubled since 2009. However, current US Food and Drug Administration buprenorphine dosing guidelines are based on studies among people using heroin, prior to the emergence of fentanyl in the illicit drug supply.ObjectiveTo estimate the association between buprenorphine dose and time to treatment discontinuation during a period of widespread fentanyl availability.Design, Setting, and ParticipantsThis retrospective cohort study used statewide Rhode Island Prescription Drug Monitoring Program data. Participants were Rhode Island residents initiating buprenorphine treatment for OUD between October 1, 2016, and September 30, 2020. Data analysis was performed from December 9, 2022, to August 10, 2023.ExposureDaily dose of buprenorphine (16 mg and 24 mg) defined starting on the day of initiation based on total quantity and days’ supply dispensed. Patients were censored on any dose change.Main Outcomes and MeasuresBuprenorphine treatment discontinuation in the 180 days following initiation, defined as a gap in treatment of more than 27 days based on prescription fill dates and days’ supply. Kaplan-Meier and Cox regression survival analyses were conducted to estimate the association between buprenorphine dose and time to treatment discontinuation, controlling for potential informative censoring and measured potential confounders.ResultsAmong 6499 patients initiating buprenorphine treatment for OUD, most were aged 25 to 44 years (57%; n = 3682), were male (61%; n = 3950), and had private (47%; n = 3025) or Medicaid (33%; n = 2153) insurance. More than half of patients were prescribed a daily dose of interest at initiation (16 mg: 50%; n = 3264; 24 mg: 10%; n = 668). In Kaplan-Meier analyses, 58% of patients discontinued buprenorphine treatment within 180 days (16 mg: 59% vs 24 mg: 53%; log-rank test P = .005). In Cox regression analyses, patients prescribed a dose of 16 mg had a greater risk of treatment discontinuation than those prescribed 24 mg (adjusted hazard ratio, 1.20; 95% CI, 1.06-1.37).Conclusions and RelevanceIn this cohort study of patients initiating buprenorphine treatment from 2016 to 2020, patients prescribed a 24 mg dose of buprenorphine remained in treatment longer than those prescribed 16 mg. The value of higher buprenorphine doses than currently recommended needs to be considered for improving retention in treatment.

A Systematic Review of State Office-Based Buprenorphine Treatment Laws Effective During 2022: Counseling, Dosage, and Visit Frequency Requirements

“…Recent studies suggest that higher dosages of buprenorphine may result in longer retention 41 -45 ; and higher dosages of buprenorphine may be particularly useful at a time when fentanyl—a very potent opioid—is increasingly the cause of overdose. 46 Furthermore, high dosages are the norm in the Veterans Health Administration.…”

Caring for Hospitalized Adults With Opioid Use Disorder in the Era of Fentanyl

“…Few data exist about dosing for patients using fentanyl; however, clinical experience and emerging evidence suggests that patients may need higher doses of methadone and buprenorphine . The heterogenous and rapidly changing drug supply means any specific dosing guidance (including the guidance outlined in this review) will likely change over time and may need to be modified to adapt to the current local drug supply, patient use patterns, and emerging evidence.…”

Trends in the Prescribing of Buprenorphine for Opioid Use Disorder, 2019-2023

“…Buprenorphine fills were stratified by the distribution of fills for days supply (1-7, 8-15, 16-27, and 28+ days) and daily dose (0-7.9, 8-11.9, 12-15.9, and 16+ mg). Longer initial days supply 24 and doses above 24 mg 25 have been associated with better outcomes. We separately calculated days supply and daily dose by Commercial and MA.…”