Risk of buprenorphine triggering sudden opioid withdrawal is low

Buprenorphine, an evidence-based treatment for opioid use disorder, is currently underprescribed because of concerns that it can cause ‘precipitated withdrawal’, in which the first dose causes sudden, intense pain and anxiety that resolves within a few hours.  A new review of the best available evidence has found that the rate of buprenorphine-precipitated withdrawal in adults with opioid use disorder is low and should not be a barrier to use.  The review is published in the scientific journal Addiction.

Lead author Dr Caroline Gregory, of the University of Ottawa, explains: “There is a lot of speculation that buprenorphine-precipitated withdrawal is a widespread problem.  This had led both doctors and patients to resist using buprenorphine to treat opioid use disorder.  Until now, we haven’t known the size of the problem.  Our study reviewed all of the available evidence to determine how often buprenorphine-precipitated withdrawal occurs.  We found that between 0 and 13.2% of adults with opioid use disorder taking their first dose of sublingual buprenorphine experienced precipitated withdrawal.  Most of the evidence was at the lower end of that range, and precipitated withdrawal symptoms were generally mild.

“This means that the best evidence we have is that buprenorphine-precipitated withdrawal is a low risk and should not stop doctors or patients from using buprenorphine.”

The review also found room for improvement.  The overall quality of the studies included in this review was poor:  many didn’t have a process for recording cases of precipitated withdrawal and many didn’t record the severity of withdrawal.  The review also found that there is no standard definition of precipitated withdrawal.  Even so, the highest-quality studies to date have consistently found low rates of precipitated withdrawal.

Dr. Gregory says, “We need better evidence to measure the true risk of precipitated withdrawal.  Until those high-quality studies are conducted, doctors and patients should not resist using this highly effective treatment for opioid use disorder.”

This systematic review looked at 26 studies of buprenorphine-precipitated withdrawal, including 5 randomized trials, all conducted between 2002 and 2023 and with a total sample size of 4,497 patients.

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For editors:

This paper is free to read online for one month after publication on the Wiley Online Library (https://onlinelibrary.wiley.com/doi/10.1111/add.16646) or you may request a copy from Jean O’Reilly, Editorial Manager, Addiction, jean@addictionjournal.org.

To speak with lead author Dr. Caroline Gregory, please contact her at the University of Ottawa by e-mail (cgregory@toh.ca).

Full citation for article: Gregory C, Yadav K, Linders J, Sikora L, and Eagles D.  Incidence of Buprenorphine-Precipitated Opioid Withdrawal in Adults with Opioid Use Disorder: A Systematic Review. Addiction. 2024. DOI: 10.1111/add.16646

Primary funding: No specific funding was required. 

Declaration of interests: The authors declare that they have no competing interests.

Addiction is a monthly international scientific journal publishing peer-reviewed research reports on alcohol, substances, tobacco, gambling, editorials, and other debate pieces. Owned by the Society for the Study of Addiction, it has been in continuous publication since 1884.