Journal Article Annotations
2023, 3rd Quarter

Addiction

Annotations by Julian J. Raffoul, MD, PhD
October, 2023

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

PUBLICATION #1 — Addiction

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

Laura C Chambers, Benjamin D Hallowell, Andrew R Zullo, Taylor J Paiva, Justin Berk, Rachel Gaither, Aidan J Hampson, Francesca L Beaudoin, Rachel S Wightman

Abstract: JAMA Netw Open. 2023 Sep 5;6(9):e2334540. doi: 10.1001/jamanetworkopen.2023.34540.

Importance:
Buprenorphine 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.

Objective:
To estimate the association between buprenorphine dose and time to treatment discontinuation during a period of widespread fentanyl availability.

Design, setting, and participants:
This 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.

Exposure:
Daily 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 measures: Buprenorphine 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.

Results: Among 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 relevance:
In 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.

Annotation

The finding:
Patients with opioid use disorder (OUD) who were prescribed a higher daily dose of buprenorphine (24 mg) were more likely to remain in treatment over six months compared with those who received a lower dose (16 mg), according to a cohort study of 6,499 patients prescribed buprenorphine in Rhode Island from 2016 to 2020. Of these patients, 57% were 25 to 44 years old and 61% were male. In total, 58% of patients discontinued buprenorphine treatment within 180 days. Of those who received 16 mg, 59% discontinued treatment compared with 53% of those prescribed 24 mg—a statistically significant difference. Current dosing guidelines for buprenorphine are based on studies among people using heroin, prior to the emergence of fentanyl in the illicit drug supply. The value of buprenorphine doses that are higher than those currently recommended should be considered for improving treatment retention in the era of synthetic opioid use disorders.

Strength and weaknesses:
However, this study was observational and although it attempted to account for measured factors that may be associated with buprenorphine dose and treatment retention, sociodemographic, social determinants of health, or other residual confounding factors may remain. Characteristics of the clinicians’ facilities may also confound the results. Furthermore, the 53% treatment discontinuation rate among patients on 24 mg suggests even this dose may be inadequate for many patients and higher doses—32mg, or more?—may need to be considered. Measurement of the above outcomes in a randomized clinical trial would be optimal to evaluate the full risks, benefits, and optimal dosing range with buprenorphine.

Relevance:
C-L psychiatrists should be familiar with strategies to improve OUD treatment. Patients prescribed a 24 mg dose of buprenorphine remained in treatment longer than those prescribed 16 mg—potentially saving lives since improved retention in buprenorphine treatment reduces risk of overdose and death. The current daily target dose of buprenorphine has been suggested to be inadequate to control symptoms of OUD in patients who used fentanyl or other synthetic opioids. Recommending higher doses of buprenorphine for patients with OUD, particularly synthetic OUD such as with fentanyl, may better treat synthetic opioid withdrawal and cravings and thereby improve treatment retention in this vulnerable patient population.