New findings suggest a dose adjustment is needed

Individuals with opioid use disorder who receive a higher daily dose of the medication buprenorphine are 20% more likely to remain in treatment compared to those prescribed a lower dose, according to a new study conducted in Rhode Island from 2016 to 2020. The study’s findings come at a critical time when the prevalence of fentanyl, a potent synthetic opioid responsible for a significant portion of overdose deaths, has raised questions about the adequacy of existing dosing guidelines.

The study, published in JAMA Network Open and supported by the National Institute on Drug Abuse (NIDA), was led by researchers from Brown University, the Rhode Island Department of Health, and NIDA. It aimed to understand the impact of buprenorphine dosing on treatment retention among individuals with opioid use disorder, particularly during a period when fentanyl became widely available.

In recent years, the opioid epidemic has devastated communities across the United States, with a staggering number of overdose deaths. Fentanyl, a synthetic opioid approximately 50 times more potent than heroin, has played a central role in this crisis. In 2021, over 70,000 overdose deaths were primarily attributed to fentanyl.

Fentanyl’s presence in the illicit drug supply has led to a need for more effective treatments for opioid use disorder. Buprenorphine, a medication that reduces opioid cravings and withdrawal symptoms, has been a crucial part of opioid use disorder treatment. However, the dosing guidelines for buprenorphine were established before the emergence of fentanyl as a dominant substance in the illegal drug market. This raises questions about whether the recommended dosages are still appropriate in the face of this new challenge.

“In the face of soaring overdose rates, it is essential that we study whether and how evidence-based treatments for opioid use disorder may need to evolve due to the rapidly changing drug supply,” said study author Laura C. Chambers, an assistant professor at Brown University School of Public Health. “There is very strong evidence that buprenorphine treatment saves lives and improves health and quality of life among people with an opioid use disorder.”

“However, clinicians and patients have suggested that higher daily doses of buprenorphine are needed to control cravings and prevent withdrawal for many people who used fentanyl than were previously needed for people who used heroin and prescription opioids (e.g., oxycodone and hydrocodone). We must be able to quickly and rigorously study these types of questions to inform treatment guidelines and ensure that we are setting patients up for success.

To investigate the impact of buprenorphine dosing on treatment retention, the researchers conducted a retrospective cohort study in Rhode Island. They analyzed data from 6,499 individuals who initiated buprenorphine treatment for opioid use disorder between 2016 and 2020.

The researchers found that patients prescribed a daily dose of 24 milligrams (mg) of buprenorphine were more likely to remain in treatment than those prescribed the recommended 16 mg dose. Specifically, individuals on the lower dose were 20% more likely to discontinue treatment within 180 days. The study’s results suggest that individuals with a higher tolerance to opioids, such as those exposed to fentanyl, may require higher buprenorphine doses to improve treatment retention.

“We aimed to answer the question: Are higher doses of buprenorphine treatment for opioid use disorder associated with improved retention in treatment when use of fentanyl (versus heroin) is more common? In short, the answer was yes,” Chambers told PsyPost.

“This finding is consistent with what we’ve heard from patients and clinicians: that, for many people who used fentanyl, the recommended 16 mg daily dose of buprenorphine does not adequately control cravings and prevent withdrawal, and that these symptoms improve with higher doses. It also makes sense given what we know about fentanyl and how it differs from heroin and prescription opioids like oxycodone and hydrocodone.”

“Not only is fentanyl more potent, but recent studies also suggest that it may lead to greater tolerance and dependence. Taken together, clinicians need to consider higher daily doses of buprenorphine (up to 24 mg) for their patients who used fentanyl. Higher doses may better control cravings and prevent withdrawal, ultimately helping patients to stay in treatment.”

But the study, like all research, includes some limitations.

“The main limitation of our study is that it was observational, meaning patients were not randomized to the 16 mg or 24 mg daily dose,” Chambers explained. “As a result, there were other factors that influenced the dose patients were prescribed, and some of those same factors may have also impacted retention in treatment. In our analysis, we aimed to account such factors when the data were available, including age, sex, health insurance, year, location of residence, and other controlled substances prescribed.”

“However, there may be other unmeasured factors that we were not able to account for, and this could bias our results. For this reason, we are hoping to conduct a randomized controlled trial of differing daily doses of buprenorphine, which would avoid this potential bias. Another important limitation of our study was that the measures were based on prescription fill data, and the information on a prescription may not reflect how the patient actually took or was instructed to take the medication.”

“Additionally, we had hoped to examine doses higher than 24 mg in our study, but the number of patients prescribed such doses during the study period was too small for a meaningful analysis,” Chambers said. “This is an important area for future research, as prior work suggests there may be dose-dependent benefits up to 32 mg.”

As part of future research, scientists plan to conduct prospective randomized clinical trials to further investigate the impact of daily buprenorphine doses, including doses up to 24 mg, on treatment retention and patient outcomes. These trials will also explore the role of other factors, such as clinician prescribing practices and patient socio-demographics, in treatment retention.

Ultimately, the findings from these trials could inform updates to opioid use disorder treatment standards, ensuring that individuals with opioid use disorder receive the most effective and tailored care.

NIDA Director Nora Volkow emphasized the importance of adapting treatments to the changing landscape of the opioid crisis, stating, “Effective treatment can save lives, but our proven treatments for opioid use disorders must evolve to match the challenges posed by the fentanyl crisis. If science continues to demonstrate that a higher dosage of buprenorphine increases treatment retention, we must re-evaluate clinical guidelines to optimize treatment and help people achieve recovery.”

The study, “Buprenorphine Dose and Time to Discontinuation Among Patients With Opioid Use Disorder in the Era of Fentanyl“, was authored by Laura C. Chambers, Benjamin D. Hallowell, Andrew R. Zullo, Taylor J. Paiva, Justin Berk, Rachel Gaither, Aidan J. Hampson, Francesca L. Beaudoin, and Rachel S. Wightman.

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