Minority of Patients With OUD Develop PW After Buprenorphine Initiation
A small group of patients with opioid use disorder (OUD) developed buprenorphine-precipitated withdrawal (PW) in emergency department or hospital settings, according to recent retrospective cohort study results published in JAMA Network Open. PW was more frequent among patients with confirmed fentanyl use.
“It is important to establish the incidence of buprenorphine PW from fentanyl because fentanyl is the predominant opioid involved in overdoses and because buprenorphine is the only US Food and Drug Administration–approved medication for OUD that is both associated with decreased mortality and available across all US treatment settings,” researchers wrote.
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The study took place at 3 academic hospitals in Philadelphia, Pennsylvania, and included adults with OUD who underwent traditional or high-dose buprenorphine initiation between January 1, 2020, and December 31, 2021. Researchers excluded those receiving low-dose buprenorphine initiation and missing documentation of opioid withdrawal severity within 4 hours of receiving buprenorphine. PW was defined as a 5-point or greater increase in Clinical Opiate Withdrawal Scale (COWS) score from baseline to within 4 hours after buprenorphine initiation.
A total of 226 patients (66.4% male; mean age 38.6 years) were included in the study and received an initial dose of at least 2 mg of sublingual buprenorphine after a COWS score of 8 or higher. Overall, 26 patients (11.5%) met criteria for PW, of which, the median change in COWS score was 9 points. Patients with confirmed fentanyl use also had higher levels of PW. Researchers also found a BMI of 30 or greater compared with less than 25 (adjusted odds ratio [AOR], 5.12; 95% CI, 1.31-19.92) and urine fentanyl concentration of 200 ng/mL or greater compared with less than 20 ng/mL (AOR, 8.37; 95% CI, 1.60-43.89) were associated with PW.
“As fentanyl adulteration increases in the drug supply and as access to buprenorphine expands,” authors noted, “future research should confirm the rate of buprenorphine PW, assess whether bioaccumulated fentanyl is responsible for PW, and determine whether BMI and urine fentanyl concentration can help clinicians optimize buprenorphine initiation for individual patients.”
Authors noted this study has several limitations. Its retrospective cohort design and limited sample size may introduce bias, confounding, and reduced power to detect small associations. High rates of missing data and the inability to distinguish new buprenorphine initiations from continued treatments further complicate findings, potentially underestimating PW incidence. Additionally, the inability to account for urine dilution in fentanyl concentration and the study's focus on hospital and ED patients limit generalizability to those initiating buprenorphine at home.
