Jessica M. Scully

A team of researchers at Yale School of Medicine (YSM) is helping determine risks and benefits for higher-than-previously recommended doses of a medication to treat opioid use disorder.

The upper daily limit of the medication, buprenorphine, was once thought to be 24 milligrams. This dosage was based on research in patients using heroin. But as fentanyl has replaced heroin in opioid use, physicians have found that dose is less effective in some patients, especially those who have used fentanyl. In response, physicians have prescribed higher buprenorphine doses for these patients. And as more physicians have seen that higher doses are effective, more have been prescribed.

But little research has been done on these high doses, according to 

, YSM associate professor (general medicine) and a research health scientist at the Department of Veterans Affairs. Many veterans are prescribed long-term opioid therapy for chronic pain, which can lead to opioid use disorder and the need for buprenorphine treatment, she noted.

“Veterans are increasingly being exposed to these higher doses, but we’re not really clear on the risk benefit ratio. Determining that is the purpose of the study,” she said.

 professor of medicine (general medicine), and 

, professor of medicine (general medicine), is working with the Veterans Affairs (VA) Connecticut Healthcare System as part of a larger study funded by the FDA. The Buprenorphine Dosing for OUD Outcomes and Studying Treatment Episodes (BOOST) study also includes VA research teams from Salt Lake City, Little Rock, and Portland, Oregon. The teams are using data from VA electronic health records, for 10 projects on how and why veterans are prescribed higher doses and their health outcomes on those higher doses.

The YSM team, using a national observational cohort created for the Veterans Aging Cohort Study (VACS), is studying the characteristics of patients prescribed high doses and how long patients remain on these doses to understand whether high doses decrease treatment dropout.

“This is such an important outcome because people face risk for overdose and death if they drop out of treatment and relapse to opioid use,” Black said.

The team is also studying how long patients stay at a lower dose before they are moved to a higher one and how higher doses versus lower doses affect additional patient outcomes. And they hope to determine what treatments are used along with buprenorphine, including for patients who need chronic pain management.

“Through our partnership with the FDA, results of this study have the potential to inform guidelines around the practice of high-dose buprenorphine prescribing for any patient in treatment for opioid use disorder,” Black said.

This project is partially funded by the U.S. Food and Drug Administration (FDA) via an Inter-Agency agreement with the Veteran Affairs (VA) [PO# 75F40124S30054] and conducted in collaboration with the VA Pharmacy Benefits Management Services (VA PBM). The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, VA, or the U.S. Government.

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Articles

Researchers at Yale School of Medicine are investigating the risks and benefits of prescribing higher doses of buprenorphine for opioid use disorder, particularly in patients exposed to fentanyl. The study, part of a larger FDA-funded project, involves collaboration with the Veterans Affairs Connecticut Healthcare System and other VA research teams. The research aims to understand patient characteristics, treatment duration, and outcomes associated with high-dose buprenorphine, potentially informing future prescribing guidelines. The study also examines the impact of concurrent treatments for chronic pain management in these patients.

Yale researchers explore the risks and benefits of higher buprenorphine doses for opioid use disorder, aiming to improve treatment outcomes for veterans.