A medication proven safe and effective in helping patients addicted to opioids may be being administered in doses too low for some of those accustomed to street drugs saturated with fentanyl, according to a study published Monday in JAMA, the Journal of the American Medical Association.
People who were prescribed a lower dose of buprenorphine to treat opioid use disorder were 20% more likely to discontinue treatment than those on a higher dose, according to researchers at Brown University and the Rhode Island Department of Health.
Dr. Wilson M. Compton, deputy director of the National Institute on Drug Abuse (NIDA) of the National Institutes of Health, said the study is the first he’s aware of that systematically compares dosing for the opioid-treatment medication.
“One of the most important ways to save people’s lives in the overdose crisis is to get them on a medication to treat the underlying opioid use disorder,’’ Compton said. “And that’s what buprenorphine is.”
In Rhode Island, 74% of the 434 drug overdose deaths in 2022 were linked to fentanyl, a synthetic opioid 50 to 100 times stronger than morphine, according to state data published on preventoverdoseri.org.
Nationally, the share of fentanyl-related drug overdose deaths in 2022 was 68%, according to preliminary data from the Centers for Disease Control and Prevention.
Dosage levels for buprenorphine were set back when the illicit opioid market was dominated by prescription painkillers and heroin, Compton said. But in recent years, as fentanyl has flooded the market, people who use illicit opioids have developed a higher tolerance. So the opioid substitutes used to treat those people, he said, may also need to be increased.
Buprenorphine, one of two FDA-approved medications – the other being methadone – considered the gold standard for treating opioid use disorders, has been shown to reduce the risk of overdose and help people stay in treatment. Unlike methadone, which patients generally can only access at specialized clinics, buprenorphine is prescribed in doctor’s offices and clinics.
More than 5,000 Rhode Island residents are receiving buprenorphine treatment, according to state health data.
The researchers in Rhode Island compared patients prescribed the target daily dose of 16 milligrams recommended by the U.S. Food and Drug Administration with those given the higher 24 mg daily dose. They analyzed data on 6,499 Rhode Island residents who initiated treatment between 2016 and 2020 with buprenorphine.
The idea for the study grew out of a buprenorphine hotline that Rhode Island launched at the start of the COVID-19 pandemic to help expand access to opioid treatment, said Dr. Rachel Wightman, an associate professor of epidemiology at Brown University and one of the study’s lead authors. While answering calls to the hotline, she said, “it really became clear that the patients who I was speaking with were doing better on higher doses of buprenorphine.”
Wightman said she shared her impressions with treatment providers doing similar work across the country, and found that they noticed a similar pattern.
“We were really seeing higher levels of opioid dependence and tolerance,” she said. “It really became clear that the patients who I was speaking with were doing better on higher doses of buprenorphine.”
Studies of patients in emergency rooms and outpatient treatment have shown that more than 16 mg of buprenorphine is safe and well tolerated in people with opioid use disorder.
And though more recent clinical guidance supports use of higher doses of buprenorphine, Wightman said, the medication’s FDA package inserts continue to recommend 16 milligrams, and some insurance companies require prior authorization to prescribe a higher dose. When a doctor is trying to help patients on a hotline or in a hospital emergency department, she said, requiring prior authorization can be a barrier to treatment.
“We’re dealing with a population … [at] extremely high risk for overdose,” including a fatal overdose, Wightman said. “And I think a 20% improvement in treatment retention is huge.”
Yet even at the higher dose of 24 mg, “an awful lot of people still drop out of treatment,’’ Compton said. “And this raises the question of, well, if 24 milligrams is better than 16 [milligrams], might 32 be better than 24?”
He said that’s an important question for future studies.
Health reporter Lynn Arditi can be reached at larditi@thepublicsradio.org. Follow her on X/Twitter @LynnArditi
