A new study led by Brown University researchers suggests there is a need to re-evaluate opioid addiction treatment recommendations in the era of fentanyl. Recent research found that patients with opioid use disorder who took low doses of buprenorphine were 20 percent more likely to end treatment compared to those who took high doses of buprenorphine. In light of the current opioid crisis and the dominance of fentanyl, the study calls for a re-evaluation of buprenorphine dosing guidelines.
The study, recently published in JAMA Network Open, focused on patients in Rhode Island between 2016 and 2020. During this period, the rise of the powerful prescription opioid fentanyl led to an increase in overdoses and deaths. The study was led by experts from Brown University, the National Institute on Drug Abuse and the Rhode Island Department of Health.
Dosing Details and Patient Response
During the study period, among participants who started buprenorphine treatment for opioid abuse, 59% were prescribed a daily dose of 16 mg and 53% were prescribed a daily dose of 24 mg, and they ended treatment within 180 days. The U.S. Food and Drug Administration recommends a daily dose of 16 mg. A complex comparison of the two groups showed that patients taking the FDA-recommended dose were more likely to discontinue treatment within 180 days than those taking the 24-mg dose. A multivariable comparison of the two study groups showed that patients taking the recommended dose were significantly more likely to discontinue treatment within 180 days than those taking the 24 mg dose.
It's important to note that the recommended daily dose was established before fentanyl became widely available. The researchers stressed that these guidelines need to be re-evaluated because the situation has changed significantly.
Importance of updated treatments
"Drugs like buprenorphine to treat opioid use disorder can save lives, but only if people start taking them and keep taking them," said study author Dr. Francesca Beaudoin, a professor of epidemiology and emergency medicine at Brown University. These drugs have been around for a long time, but fentanyl has not. We must reevaluate and update treatment guidelines to address today's opioid crisis -- otherwise, we are putting lives at risk. This study shows that people who are prescribed higher doses of buprenorphine tend to stay on it longer."
Medications to treat opioid use disorder, including buprenorphine, can safely and effectively help reduce opioid use and overdose and help patients recover by reducing opioid cravings and easing withdrawal symptoms, researchers say. Their findings build on accumulating evidence on the safety and efficacy of higher doses of buprenorphine: Studies have shown that doses above 16 mg of buprenorphine are safe and well-tolerated in patients with opioid use disorder in emergency department and outpatient treatment settings.
The rise of fentanyl and current treatment guidelines
In 2021, of the nearly 107,000 overdose deaths reported, more than 70,000 were caused primarily by fentanyl. This potent synthetic opioid is about 50 times more powerful than heroin. The ubiquity of fentanyl in the drug supply and the resulting increase in overdose deaths has raised questions about whether existing dosing guidelines for buprenorphine should be modified to better address the unique challenges posed by this potent opioid.
"Medications for treating opioid use disorder have been around for a long time, but the same cannot be said for fentanyl. We must reevaluate and update treatment guidelines to address today's opioid crisis - otherwise, we are putting lives at risk." -Francesca L. Beaudoin, MD, chair of the Department of Epidemiology, School of Public Health, Brown University.
Currently, FDA-approved labeling states that the maintenance dose should be between 4 and 24 mg, with a recommended target dose of 16 mg per day for most patients. Recommended treatment dosages can vary widely based on an individual's needs and response to medications. "The current recommended target dose for buprenorphine was derived from studies conducted before fentanyl was widely used," said study author Dr. Rachel Whiteman, associate professor of emergency medicine and epidemiology at Brown University's Warren Alpert School of Medicine. Our findings suggest that increasing the dose of buprenorphine may help improve treatment outcomes in these individuals. We have a responsibility to help our patients succeed. "
Analyze previous data and future steps
For the study, researchers retrospectively examined data on 6,499 Rhode Island residents who began using buprenorphine as part of opioid use disorder treatment between 2016 and 2020, a period when fentanyl emerged and became dominant. Our goal was to estimate the relationship between a patient's daily dose of buprenorphine and 180-day treatment retention, which is consistent with the U.S. Centers for Medicare and Medicaid Services' minimum treatment duration for measuring continuity of treatment for opioid use disorder.
Most patients are male, between the ages of 25 and 44, and have private or Medicaid insurance. At the time of initiating buprenorphine treatment, approximately 21% of patients (1,343 people) were prescribed 8 mg, 50% (3,264 people) were prescribed 16 mg, and 10% (668 people) were prescribed 24 mg. The number of patients prescribed doses above 24 mg during the study period was small (0.2%, or 15 patients) and therefore could not be analyzed.
Patients prescribed the 24 mg buprenorphine dose continued treatment longer than those prescribed the 16 mg recommended dose. The latter were 20% more likely to discontinue treatment than those prescribed the 24 mg dose.
The research team plans to further conduct this research in the future. Their goal is to launch a clinical trial to evaluate the effectiveness of daily doses of buprenorphine up to 24 mg in improving treatment persistence and reducing the risk of overdose and death. In this trial, researchers will also investigate the role of other factors that may be associated with retention in treatment, including clinicians' prescribing practices and patients' sociodemographics and living circumstances. The trial results will ultimately help update treatment standards for opioid use disorder.