麻豆传媒

Extended-release 7-day injectable buprenorphine was safe and tolerable for most patients who had minimal-to-mild opioid withdrawal, a nonrandomized trial found.

Among 100 adult patients with minimal-to-mild opioid withdrawal scores who were given a 24-mg dose of extended-release buprenorphine, only 10 people (10%, 95% CI 4.9%-17.6%) saw a 5-point or greater jump in withdrawal symptoms within 4 hours of injection, reported Gail D'Onofrio, MD, of the Yale School of Medicine in New Haven, Connecticut, and colleagues.

Scores were determined using the Clinical Opiate Withdrawal Scale (), an 11-item questionnaire that assesses opioid withdrawal levels based on resting pulse rate, sweating, gastrointestinal upset, and other symptoms. A higher score indicates a greater degree of withdrawal. A COWS score of 0 to 7 represents minimal-to-mild withdrawal. Patients who saw benefit with the extended-release agent had COWS scores 4 to 7.

The researchers also reported in that of those 10 patients, 7% (95% CI 2.9%-13.9%) saw symptoms escalate to moderate or greater withdrawal within 4 hours, while 2% (95% CI 0.2%-7.0%) experienced "precipitated withdrawal" within 1 hour of injection. Precipitated withdrawal is akin to the experience of receiving naloxone (Narcan) and can involve vomiting, diarrhea, and other unpleasant side effects, D'Onofrio explained to 麻豆传媒.

Overall, seven patients (7%, 95% CI 2.9%-13.9%) went through precipitated withdrawal within 4 hours of injection, including two of 63 participants (3.2%) with a COWS score of 4 to 7 and five of 37 participants (13.5%) with a COWS score of 0 to 3.

The study examined whether patients with untreated opioid use disorder (OUD) and minimal-to-mild withdrawal could tolerate a 7-day dose of buprenorphine. Patients with OUD typically aren't treated with medication until they are in significant withdrawal, due to fear of precipitated withdrawal. For that reason, "[n]o one has ever even attempted to give buprenorphine in that [0 to 7] range," D'Onofrio said.

Few people with a COWS score of 4 or more experienced precipitated withdrawal in the study, suggesting "it would be very reasonable and safe to use our 7-day injectable" in that population, she noted.

"And it's 7 days," D'Onofrio said, "so that's even better [than sublingual buprenorphine] because you have 7 days to make people feel better and not have to internally decide 'Am I going to take my medicine today or not?'"

However, the roughly 13% incidence of precipitated withdrawal in the 0 to 3 COWS group indicated those patients are not candidates for extended-release buprenorphine, she clarified.

Still, "this is a real game-changer for emergency physicians and clinicians, even in the clinic, who would be able to induce people on buprenorphine much earlier than they previously could have," D'Onofrio said.

The trial was conducted in four emergency departments. Mean patient age was 36.5 years, and most were male. About half of study participants were white (51%); 35% were Black or African American, and 13% were Hispanic or Latino.

Just under half (48%) reported unstable housing in the last 12 months and 36% currently had unstable housing. Most patients had public insurance and tested positive for fentanyl.

Outcomes were measured daily for 7 days using telephone surveys and in person on day 7. Recruitment took place from 2020 to 2023.

Participants were given gift cards as compensation with a maximum value of $200. They were referred to community-based programs or clinicians for ongoing OUD treatment.

Site pain scores were low immediately after injection and after 4 hours. On any of the 7 days, between 33% and 43% of patients who responded to surveys reported no cravings, and between 78% and 85% reported no use of opioids. Overall, 60% of patients reported no days of opioid use. Most patients (73%) were still engaged in treatment on day 7.

With traditional sublingual buprenorphine, "it takes days to get a steady state and people are still going to crave, and when they're craving, they're going to use opioids," D'Onofrio said. In contrast, the extended-release formulation takes several hours to reach "a good point ... and it will stay up for a long time ... so you're not getting peaks and troughs," she stated.

Five serious adverse events (AEs) occurred that required hospitalization; two were associated with treatment.

Limitations included a lack of a control group and the study's small size and strict eligibility criteria. The researchers had some discretion in selecting patients with COWS score of 0 to 3, which may have led to selection bias.

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