Are Buprenorphine Doses Too Low?

If patients were prescribed antibiotics at too-low doses, it would be obvious that they had little chance of successful treatment. The same is true for patients with opioid use disorder, said Smita Das, M.D., Ph.D., M.P.H., chair of APA’s Council on Addiction Psychiatry. “If we don’t sufficiently treat these patients at least per guideline dosing, we may be setting them up for failure,” she said.

Underprescribing of buprenorphine has long been concerning, Das said. She often has patients who present to her on doses of buprenorphine below 16 mg—the target daily dose recommended by the U.S. Food and Drug Administration (FDA). Currently, dosing guidelines include an upper limit of 24 mg per day. Yet a new study suggests that the upper limit may be ideal for most patients.

According to a study published in JAMA Network Open in September, patients who received 24 mg of buprenorphine were significantly more likely to remain in treatment over six months compared with those who received 16 mg.

The FDA’s recommendations around buprenorphine prescribing were developed before fentanyl emerged in the illicit drug supply. Some physicians have suggested that 16 mg of buprenorphine may be inadequate to control withdrawal and cravings among patients who used fentanyl, wrote lead author Laura Chambers, Ph.D., M.P.H., and colleagues. Chambers is an assistant professor of the practice of epidemiology at Brown University.

Chambers and colleagues conducted a retrospective study using data from the Rhode Island Prescription Drug Monitoring Program. They included patients who initiated buprenorphine treatment for opioid use disorder for the first time between October 2016 and September 2020. Each patient was followed for 180 days after initiation.

The authors categorized patients as having discontinued treatment if they had a gap in treatment of more than 27 days based on prescription fill dates and days’ supply. To account for slight variations in prescribing, the authors categorized patients who received daily doses in the 14-18 mg range in the 16 mg group, and patients who received doses in the 22-26 mg range in the 24 mg group.

A total of 6,499 patients were included in the study, 57% of whom were 25 to 44 years old and 61% of whom were male. The initial daily dose for most patients was 8 mg (21%) or 16 mg (50%), and only 10% were initially prescribed a 24 mg dose. In total, 58% of patients discontinued buprenorphine treatment within 180 days. Of those who received 16 mg, 59% discontinued treatment compared with 53% of those prescribed 24 mg—a statistically significant difference, according to Chambers and colleagues.

“Effective treatment can save lives, but our proven treatments for opioid use disorders must evolve to match the challenges posed by the fentanyl crisis,” National Institute on Drug Abuse (NIDA) Director Nora Volkow, M.D., said in a news release. NIDA funded the study by Chambers and colleagues. “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.”

Those who use fentanyl may require a higher buprenorphine dose because of the drug’s high potency and unique profile, which leads patients to develop greater tolerance and physiologic dependence, Das said. Additionally, fentanyl has high lipophilicity, meaning it sticks around in fat structures longer than other illicit opioids. This may lead patients who use fentanyl to have longer, more intense withdrawals that need clinical attention, Das said.

Some physicians are overly cautious when they prescribe buprenorphine, but that extreme caution may be unnecessary due to the medication’s safety profile, especially compared with a full agonist opioid, she said.

There are several studies underway exploring the optimal buprenorphine dose, she noted. “My hope is that the guidelines evolve with the newer findings,” Das said. “In the meantime, clinicians would benefit from treating the patient’s symptoms.” ■