D'Onofrio 2023: precipitated withdrawal was rare when EDs started buprenorphine

What they tested

Within an ongoing trial run from June 2020 to October 2022, people with opioid use disorder at 28 emergency departments were randomly assigned to start standard buprenorphine under the tongue or CAM2038, a 7-day buprenorphine injection. They needed urine tests positive for opioids and negative for methadone, and a Clinical Opiate Withdrawal Scale (COWS) score of 4 or more. They were observed for 2 hours.

Precipitated withdrawal, a sudden worsening of withdrawal caused by the medicine itself, was defined in advance as a marked rise in COWS score (5 points or more) needing extra buprenorphine and other medicines. Suspected cases were recorded as they happened and checked by expert reviewers. Pregnant people and people admitted to hospital were excluded.

What they found

Of 1,200 people enrolled, 9 (0.76%) had precipitated withdrawal: 5 who got buprenorphine under the tongue and 4 who got the injection.

All 9 had fentanyl in their urine, 7 along with other drugs. Most people who didn't have precipitated withdrawal also used fentanyl, and the authors found nothing that marked out who would get it. Time since last use ranged from 8 to more than 24 hours.

Worst symptoms came 20 to 116 minutes after the dose. Eight people were discharged after their symptoms resolved, after 2 hours 50 minutes to 22 hours 39 minutes in the emergency department, and 1 left against medical advice.

The authors say this rate of under 1% is similar to rates reported in people using heroin or prescription opioids, and strikingly different from what retrospective studies had found.

Limits

• People were watched for 2 hours, so cases after discharge could have been missed, although 86% were reached at 7 days.
• Fentanyl analogues or nitazenes that the tests didn't pick up may have played a part in some cases.
• It excluded pregnant people and people admitted to hospital, so it covers emergency department patients who went home.

What it means if you're considering naltrexone

This study is about buprenorphine. It found that sudden withdrawal when starting buprenorphine in the emergency department was rare, even with fentanyl common. Naltrexone has its own rules for avoiding precipitated withdrawal, covered in the site's precipitated withdrawal guide.