Opioid Treatment Strategies Shift As Researchers Advocate for Higher Buprenorphine Dosages

Recent research has uncovered that people with opioid use disorder on a lower dose of buprenorphine were 20% more likely to end treatment compared to those on a higher dose. The study calls for a reevaluation of buprenorphine dosing guidelines in light of the present opioid crisis and the dominance of fentanyl.

A new study led by Brown University researchers suggests a need to reevaluate opioid addiction treatment recommendations in the era of fentanyl.

New research reveals that individuals diagnosed with opioid use disorder who received a lower buprenorphine dose were 20% more likely to abandon their treatment compared to those on a higher dosage.

This study, which was recently published in JAMA Network Open, concentrated on patients from Rhode Island between 2016 and 2020. This period marked the rise of the powerful prescription opioid, fentanyl, which contributed to an escalation in overdoses and fatalities. The research was spearheaded by experts from Brown University, the National Institute on Drug Abuse, and the Rhode Island Department of Health.

Dosage Details and Patient Response

During the study, among the participants initiating buprenorphine treatment for opioid misuse, 59% prescribed a daily dose of 16 milligrams and 53% with a 24-milligram dose ended their treatment within 180 days. The FDA’s recommended daily dosage is 16 milligrams. An intricate comparison between these two groups showed that individuals receiving the FDA’s advised dose were more likely to cease treatment within 180 days compared to those on a 24-mg dosage. A multivariable comparison of these two study groups showed patients prescribed the recommended dose were significantly more likely to discontinue treatment over 180 days compared to those prescribed 24 mg.

Notably, the recommended daily dosage was established before the widespread emergence of fentanyl. The researchers emphasized that these guidelines need reevaluation since the situation has drastically changed.

The Importance of Updated Treatment

“Medications for opioid use disorder, such as buprenorphine, are life-saving, but only if people start them and stay on them,” said study author Dr. Francesca Beaudoin, a professor of epidemiology and emergency medicine at Brown. “These medications have been around for a long time, but fentanyl has not. It is imperative that we reevaluate and update treatment guidelines to account for today’s opioid crisis — otherwise, we are putting lives at risk. This study indicates that people who are prescribed higher doses of buprenorphine tend to stay on it longer.”

Medications for opioid use disorder, including buprenorphine, can safely and effectively support reduction in opioid use and overdose as well as recovery by decreasing opioid cravings and easing withdrawal symptoms, the researchers said. Their findings build upon accumulating evidence of the safety and efficacy of higher doses of buprenorphine: Studies have shown that more than 16 milligrams of buprenorphine is safe and well tolerated in people with opioid use disorder in emergency department and outpatient treatment settings.

Rise of Fentanyl and Current Treatment Guidelines

In 2021, of nearly 107,000 overdose deaths reported, more than 70,000 were primarily due to fentanyl. This powerful synthetic opioid is approximately 50 times stronger than heroin. The ubiquity of fentanyl in the drug supply and resulting overdose death rate increase have raised questions about whether existing dosing guidelines for buprenorphine should be modified to better address the unique challenges posed by such a potent opioid.

“Medications for opioid use disorder have been around for a long time, but fentanyl has not. It is imperative that we reevaluate and update treatment guidelines to account for today’s opioid crisis — otherwise, we are putting lives at risk.”

— Francesca L. Beaudoin. M.D., Ph.D. Chair of Epidemiology, the Brown University School of Public HealthManuel Aravena

Currently, labeling approved by the FDA states that maintenance doses should range from 4 to 24 milligrams, with a recommended target dose of 16 milligrams per day for most patients. Recommended doses for treatment can also vary widely depending on the individual’s needs and response to the medication.

“The current recommended target dose of buprenorphine was derived from studies conducted prior to the widespread availability of fentanyl,” said study author Dr. Rachel Wightman, an associate professor of emergency medicine and epidemiology at the Warren Alpert Medical School of Brown University. “Now, we’re seeing people with higher levels of tolerance to and dependence on opioids, and our findings suggest that a higher buprenorphine dose may help improve treatment retention for these individuals. We have a responsibility to set patients up for success.”

Analyzing Previous Data and Future Steps

For the study, the investigators retrospectively examined data from 6,499 Rhode Island residents initiating buprenorphine as part of treatment for opioid use disorder from 2016 to 2020, a period of fentanyl emergence and predominance. The goal was to estimate the association between patients’ daily buprenorphine dose and retention in treatment over 180 days, a timeframe that aligns with the minimum treatment period considered by the U.S. Centers for Medicare and Medicaid Services to measure treatment continuity for opioid use disorder.

Most patients were male, ages 25 to 44 years, and had private or Medicaid insurance. At the start of buprenorphine treatment, approximately 21% (1,343 patients) were prescribed 8 mg, 50% (3,264 patients) 16 mg, and 10% (668 patients) 24 mg. Those prescribed more than 24 mg were unable to be analyzed due to the small number (0.2%, or 15 patients) prescribed such doses during the study period.

Patients prescribed a 24-mg dose of buprenorphine continued treatment for a longer period than those prescribed the recommended 16-mg dose. The latter cohort was 20% more likely to discontinue treatment than those prescribed 24 mg.

The research team has future plans to further this study. They aim to initiate a clinical trial to evaluate the outcomes of daily buprenorphine doses of up to 24 mg in improving treatment retention and reducing the risk of overdose and death. Within the trial, the researchers will also investigate the role of other factors that may be associated with treatment retention, including clinician prescribing practices, as well as patient socio-demographics and life circumstances. Findings from the trial could ultimately help inform updates to opioid use disorder treatment standards.

Reference: “Buprenorphine Dose and Time to Discontinuation Among Patients With Opioid Use Disorder in the Era of Fentanyl” by Laura C. Chambers, PhD, MPH; Benjamin D. Hallowell, PhD, MPH; Andrew R. Zullo, PharmD, PhD; Taylor J. Paiva, MPH; Justin Berk, MD, MPH, MBA; Rachel Gaither, BS; Aidan J. Hampson, PhD; Francesca L. Beaudoin, MD, PhD and Rachel S. Wightman, MD, FACMT, 18 September 2023, JAMA Network Open.
DOI: 10.1001/jamanetworkopen.2023.34540

The study was funded by the National Institute on Drug Abuse, part of the National Institutes of Health under award number UG3DA056880. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.