High-dose buprenorphine in the ED could be safe for some patients

Abstract

Doses of buprenorphine well above the established standards (>12 mg) administered in the emergency department are safe and well-tolerated in individuals experiencing opioid withdrawal symptoms, says a new case series published by Herring and colleagues in the July 2021 issue of JAMA. The authors’ findings suggest that a relatively high buprenorphine induction dose, in certain patient populations that do not respond to current recommended induction regimens, may allow for a paradigm shift in common opioid use disorder (OUD) treatment modalities. The clinical algorithm presented in the study’s design allows for a more rapid response to withdrawal symptoms while also removing barriers to short-term medication access. The authors hope that by rapidly achieving therapeutic levels of buprenorphine and extending buprenorphine’s duration of action, it will potentially improve patient engagement in longer-term addiction treatment programs. Herring and colleagues conducted a retrospective review of patient electronic health record data from Highland Hospital Emergency Department in Oakland, CA in 2018. The authors identified specific OUD patients who did not have their withdrawal symptoms relieved by current guideline-recommended buprenorphine induction therapy as outlined by the Substance Abuse and Mental Health Services Administration (SAMHSA). Patients who had a COWS score (Clinical Opioid Withdrawal Scale) of 8 or more after receiving 8 mg to 12 mg of buprenorphine in the ED could be escalated to what the authors refer to as the “high-dose induction pathway,” in which the patient could receive up to 32 mg of buprenorphine, provided they showed no clinical signs of sedation, respiratory depression, or other complicating factors. Additionally, the participating providers could discharge the patient with a prescription for 16 mg of buprenorphine daily until follow-up at an addiction treatment clinic. Of the 579 opioid withdrawal ED visits during the study’s timeframe, 366—or 63.2%—were escalated to the high-dose induction pathway. Additionally, of all the buprenorphine dose totals, nearly one-fourth of them were equal to 28 mg or more. The high-dose intervention appears to have been very well-tolerated, with only one case experiencing precipitated withdrawal symptoms after receiving 24 mg of buprenorphine. In fact, of the 5 total cases of precipitated withdrawal recorded, 4 of them occurred after 8 mg of buprenorphine, but resolved after their doses were escalated to 28 mg total. Overall, there were no serious adverse effects related to buprenorphine recorded during the study, including sedation, hypoxia, or naloxone rescue in the ED 24 hours after discharge. It has been well-established that allowing withdrawal treatment through EDs improves patient engagement in addiction treatment programs. However, according to buprenorphine (specifically SUBUTEX) drug label information from 2017, “in some studies, gradual induction over several days led to a high rate of drop-out of buprenorphine patients during the induction period.” The drug labeling recommends that an adequate treatment dose, titrated to clinical effectiveness, should be achieved as rapidly as possible. Currently, the 2021 Treatment Improvement Protocols—the official guidance document by SAMHSA—recommends buprenorphine 2 mg to 4 mg, followed by a second dose of 2 mg to 4 mg after approximately 2 hours, with a maximum of 8 mg to 12 mg on day 1 and 16 mg on day 2 via a referred addiction clinic. However, this guidance may be too uniform and not adequate for patients who require a higher dosing strategy. The authors imply that the current standard often prolongs the time for maximum saturation of μ-opioid receptors and reduction in cravings. Furthermore, they state that it assumes the patient has adequate access to a buprenorphine prescription for the second day, which is often not the case. The treatment algorithm presented by Herring and colleagues is a good step forward for redefining current recommendations with regard to opioid addiction treatment in the ED. While the study may be a retrospective case series at a single site, it represents a practical application (with a well-represented patient population) for adopting a relatively safe high-dose treatment algorithm into routine practice. This new treatment technique could help prevent the inadvertent prolongation of withdrawal symptoms that current guidance may yield and improve patient follow-up and retention with addiction centers.