Higher Daily Buprenorphine Doses Help Manage OUD

Higher daily buprenorphine doses may help patients better manage opioid use disorder (OUD), data from a National Institutes of Health (NIH) study suggested.

The new data highlight that the dose size currently recommended by the US Food and Drug Administration (FDA) and insurance caps on doses are outdated and harmful in the age of fentanyl overdoses, according to the American Medical Association (AMA) and physicians who have studied the issue.

Findings of the study, led by Sarah Axeen, PhD, with the Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles, were published on September 25 in JAMA Network Open.

The researchers reviewed insurance claims data from more than 35,000 people diagnosed with OUD who started on buprenorphine treatment between 2016 and 2021. They found that 12.5% had an emergency department (ED) or inpatient visit related to behavioral health within the study period.

They analyzed whether a patient’s buprenorphine dose was linked with the length of time between treatment start and an ED or inpatient visit.

Higher Doses, Better Outcomes

The FDA’s recommended target dose for buprenorphine is 16 mg/d. Axeen’s team found that those taking higher daily doses (> 16 to 24 mg) took 20% longer to have an ED or inpatient visit related to behavioral health within the first year after receiving treatment than those who took > 8 to 16 mg/d.

“Those taking daily doses of more than 24 mg of buprenorphine went 50% longer before having a subsequent emergency or inpatient healthcare visit related to behavioral health within the first year after receiving treatment, compared to those receiving > 8 to 16 mg a day,” the researchers said in a press release.

AMA Says the Findings Should Change Policies

Bobby Mukkamala, MD, president-elect of the AMA and Chair of the AMA Substance Use and Pain Care Task Force, said the association welcomed the study findings and urged policymakers and insurance providers to act on them with updated policies.

“The findings support AMA policy calling for flexibility in buprenorphine dosing, allowing patients to receive doses exceeding FDA-approved limits when clinically recommended by their prescriber,” he said in a statement. “Policymakers must take note of these findings and the growing body of evidence that further affirm buprenorphine as a safe, effective, and lifesaving tool in the fight against the illicit fentanyl overdose epidemic. It is also critically important for health insurance companies, Medicaid, and Medicare to remove dosage caps for buprenorphine.”

‘Tangible Economic Impact’

Lucinda Grande, MD, a family physician and addiction specialist with Pioneer Family Practice in Lacey, Washington, said in an interview that she was happy to see this study because “it is the first buprenorphine dose study that addresses an outcome with a tangible economic impact that would affect the bottom line of payers and healthcare systems” and may capture the attention of policymakers in changing what she says are outdated recommendations.

“This study is also unusual because it looked specifically at the dose range above 24 mg. Even though that top tier included only a tiny proportion (1.8%) of patients, it was the group that had the greatest long-term benefit from buprenorphine,” Grande said, adding that other studies have not included that high a dose.

Grande, who published on a related topic in 2023, noted that Medicaid patients were excluded from the current study, and they make up a substantial portion of those using buprenorphine for OUD. Had they been included, she said, she suspects the evidence would have been even stronger in favor of higher doses.

Physicians can prescribe higher doses off-label, but buprenorphine is expensive, and some insurers have caps based on the FDA recommendations. Grande says she rarely prescribes > 32 mg/d, and the patients who need the higher doses often have chronic pain. “In Washington State,” she said, “we have had the luxury of prescribing up to 32 mg daily to Medicaid patients for years. I have had a lot of opportunity to work in that dose rage for people who really need it, and I can really see a difference.”

As fentanyl has grown into the primary illicit opioid, she says, the FDA recommendations for buprenorphine have become progressively weaker.

“Fentanyl is 50 times more potent than heroin, the opioid prevalent when the FDA guidelines were written,” she said. “It’s like a popgun that you’re using against a cannon.”

This manuscript was prepared with support from the National Institute on Drug Abuse. Axeen reported no relevant financial disclosures. Co-author Jessica S. Merlin reported grants from Cambia Health Foundation outside the submitted work. Adam J. Gordon reported grants from NIH and the Veterans Affairs (institution) during the conduct of the study; he reported service as editor-in-chief with the Association for Multidisciplinary Education and Research in Substance use and Addiction. Bradley D. Stein reported grants from the NIH during the conduct of the study. Mukkamala and Grande reported no relevant financial relationships.

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, Northwestern Magazine, and Nurse.com and was an editor at the Chicago Sun-Times, The Cincinnati Enquirer, and St. Cloud Times. Follow her on X@MLfrellick