Patients who received higher doses of buprenorphine, a common medication used to alleviate opioid withdrawal and cravings, were less likely to be hospitalized and less likely to discontinue treatment, according to a new study.
The findings run counter to federal guidelines about buprenorphine dosing. Currently, the Food and Drug Administration recommends a target dose of 16 mg. But as fentanyl has come to dominate the U.S. drug supply, addiction treatment providers across the country have reported that patients seeking to reduce or stop their illicit opioid use often require significantly higher doses than in years past.
The paper, published Wednesday in JAMA Network Open, found that patients receiving 24 mg or more were less likely to visit the emergency room or require other inpatient care than those receiving lower doses.
Initially, the paper’s authors sought to examine whether higher buprenorphine doses were linked to harmful outcomes, said Sarah Axeen, the director of data and analytics at the USC Schaeffer Center for Health Policy and Economics and the paper’s lead author.
But “instead of finding evidence of no harm, we actually found a benefit,” she said. “Patients receiving higher doses were less likely to end up in the emergency department, and if they did, it took them longer to get there.”
Buprenorphine and methadone, another medication used to alleviate opioid withdrawal and cravings, are viewed as the “gold standard” for treating opioid use disorder. But in recent years, as the drug supply has grown more potent, it’s become more difficult for patients seeking care to transition from fentanyl to the addiction medications.
Buprenorphine, commonly known by the brand name Suboxone, can cause “precipitated withdrawal” if not administered correctly, potentially causing pain, anxiety, sweating, and gastrointestinal distress, among other symptoms. The medication is itself an opioid, but binds to the brain’s opioid receptors differently than pain medications or fentanyl, often “outcompeting” other opioid molecules for receptor space despite not providing the same euphoric or analgesic effect.
In response, addiction doctors have turned to increasingly creative methods for starting patients on buprenorphine, including large “loading” doses, “microdosing,” and even accompanying the addiction medication with small amounts of ketamine.
The new paper adds to a growing body of evidence that higher buprenorphine doses are safe and can help patients remain in treatment. Another study published this year showed that higher initial buprenorphine doses are associated with lower mortality, and the American Society of Addiction Medicine has also advocated for giving clinicians more flexibility to use the dose they feel is medically appropriate.
“This would help support the notion that you could go even higher than 24 mg,” Axeen said. “The broader takeaway is that we need to make sure these higher dosages are available to people who need them.”
Despite the enthusiasm surrounding larger buprenorphine doses, however, they remain harder to access. Addiction medications, including buprenorphine, still face significant stigma, leading many doctors to avoid prescribing it in the first place. Among those that do, a combination of the prevailing medical culture, prior authorization requirements from insurers, and the FDA recommendations prevent them from prescribing doses exceeding 16 or 24 mg.
Patients who receive smaller doses “are going to fail, and that’s the whole point,” said Edwin Chapman, a doctor who has practiced addiction medicine in Washington for over 45 years and fought for years for the District of Columbia to raise its longtime dosing cap.
“We’ve had a number of patients, depending on the insurance company, that didn’t get the right dose because of the state regs or insurance caps and prior authorization,” Chapman said. “We recognized this in my practice in about 2015 or 2016, because we already had some patients who were testing positive for fentanyl, and we observed that their comfort level increased as they had their dose increased up to 32 mg.”
Federal agencies are already aware of the debate. In February, the Substance Abuse and Mental Health Services Administration hosted a “listening session” in conjunction with the FDA and National Institute on Drug Abuse to examine whether current buprenorphine doses were sufficient.
According to a transcript, one presentation featured a Canadian doctor who reported a “strong sense that safety is not a significant issue” when it comes to higher buprenorphine doses, citing data that only a minuscule portion of opioid overdoses in British Columbia involve the medication.
In light of the new study, Chapman expressed hope that the growing body of evidence and changing climate surrounding buprenorphine prescribing could prompt the FDA to change its dosing guidelines. Though the guidelines are not binding, they often factor into insurance companies’ decisions regarding prior authorization and are sometimes misconstrued as hard caps.
“Unfortunately, a lot of those insurance companies and states are still following the current FDA recommendations,” Chapman said. “So hopefully the FDA will make the necessary changes.”
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