Varshneya 2022: buprenorphine-precipitated withdrawal after fentanyl use

What they tested

People seeking treatment for opioid use disorder at 49 US addiction treatment centers reported the withdrawal symptoms they'd had after taking buprenorphine and, for comparison, after taking methadone. The researchers looked at how the timing of their last fentanyl use related to severe withdrawal.

Precipitated withdrawal is withdrawal that starts suddenly when a medicine pushes other opioids off the brain's opioid receptors. Buprenorphine can cause it in people who have recently used fentanyl, but how often had not been established.

What they found

Taking buprenorphine within 24 hours after fentanyl was linked to higher odds of severe withdrawal (OR 5.202, 95% CI 1.979-13.675). Taking it 24 to 48 hours after fentanyl was also linked to higher odds (OR 3.352, 95% CI 1.237-9.089). An odds ratio above 1 means higher odds.

Of people who waited less than 24 hours after fentanyl, 22.19% (152 of 685) reported severe withdrawal with buprenorphine and 11.56% (23 of 199) with methadone.

Methadone taken after fentanyl was not linked to significantly higher rates of withdrawal, which the authors say suggests the effect is specific to buprenorphine.

Limits

• It relied on people's own reports of past withdrawal, not symptoms measured by staff at the time.
• It is a survey, so it shows links between timing and withdrawal rather than proving cause.

What it means if you're considering naltrexone

For someone weighing buprenorphine against naltrexone for opioid use disorder, it shows that recent fentanyl use matters when buprenorphine is started. Naltrexone carries its own risk of precipitated withdrawal in anyone with opioids still in their system, covered in the site's precipitated withdrawal guide.