High-Dose Buprenorphine Induction for Opioid Use Disorder Safe, Effective Option


Data show 3 life-threatening adverse events required intervention, but were unrelated to buprenorphine induction.

Andrew A. Herring, MD

Andrew A. Herring, MD

While the initiation of buprenorphine for the treatment of opioid use disorder (OUD) in the emergency department (ED) is effective in reducing mortality and morbidity, there are limitations in both the timing and dose of buprenorphine after ED discharge.

Investigators, led by Andrew A. Herring, MD, Department of Emergency Medicine, Highland Hospital — Alameda Health System, examined the safety and tolerability of an ED high-dose (>12 mg) buprenorphine induction for patients with OUD.

The team found the induction of high-dose buprenorphine was a safe and well-tolerated treatment in patients with untreated OUD, and did not result in increased incidence of precipitated withdrawal or other adverse event.


Investigators performed a retrospective electronic health record (EHR) review of patients aged ≥18 years treated with SL-buprenorphine at a large, urban, safety net ED in Oakland, California between January - December 2018.

Demographic information, including self-reported race and ethnicity, was included in the analysis to describe the demographic profile of patients receiving buprenorphine treatment in the ED.

The high-dose ED buprenorphine induction included a dose option up to 32 mg SL to increased magnitude and duration of opioid withdrawal suppression.

Further, the selection of patients for high-dose buprenorphine induction (≥12 mg SL-buprenorphine) was determined based on a patient’s history, vital signs, physical examination findings, and evaluation of complicating factors.

The team also used scoring systems such as the Clinical Opioid Withdrawal Scale (COWS; mild, 5-12; moderate, 13-24; severe, >25).

Patients deemed clinically appropriate for buprenorphine induction received an initial dose of 4 - 8 mg SL based on level of withdrawal, with reassessment in 30 - 45 minutes following.

Investigators noted doses ≤12 mg could be administered to achieve minimal to mild withdrawal, with a COWS score of <8.

In addition, patients without medical complications, but barriers to access to buprenorphine after discharge were offered the high-dose induction pathway.

The team noted the dosing could be done in increments of 4-8 mg, or the full 24 mg at once, depending on the patient’s level of withdrawal.

Primary outcomes included the occurrence of precipitated withdrawal and any other serious adverse event attributable to buprenorphine administration (sedation, decreased respiratory rate, hypoxia, naloxone rescue administration in ED or 24 hours after discharge).

Data analysis was performed from April 2020 - March 2021.


A total of 391 ED patients were identified as treated with SL-buprenorphine between January - December 2018 over a total of 579 ED visits.

Demographic information included a median age of 36 years, 68.3% (n = 267) men, 43.5% (n = 170) Black and 14.6% (n = 57) were Hispanic.

Further, 22.5% of patients were homeless (n = 88), with 41.2% (n = 161) of patients having a comorbid non-substance use-related psychiatric disorder. Over half (53.5%) of patients had never been treated with buprenorphine.

Investigators found there were 366 (63.2%) high-dose inductions using more than 12 mg of SL-buprenorphine, including 138 doses ≥28 mg.

The mean length of stay in the ED was 2.4 hours (1.6 - 3.75) and most patients were assigned as low severity.

In addition, the team noted 5 cases of precipitated withdrawal, with 4 cases occurring after the typical dosing of 8 mg unrelated to high-dose buprenorphine.

They noted 3 life-threatening adverse events requiring urgent intervention, but they were determined to be unrelated to buprenorphine induction.

A total of 45 participants had return visits within 24 hours of discharge, but investigators observed no cases of precipitated withdrawal, opioid overdose, sedation, respiratory depression, or other adverse event attributed to buprenorphine treatment.


Investigators concluded the high-dose buprenorphine treatment pathway was determined to be a safe and effective method of induction at the single, urban ED.

“Our findings suggest that the high-dose induction pathway is safe, addresses withdrawal symptoms rapidly, removes barriers to short-term medication access, and extends the duration of action of buprenorphine, all of which offer substantial benefit to the individual and potentially improve follow-up,” investigators wrote.

The study, “High-Dose Buprenorphine Induction in the Emergency Department for Treatment of Opioid Use Disorder,” was published online in JAMA Network Open.

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