Buprenorphine initiation from fentanyl using low-dose intramuscular ketamine: a pilot study

Source:

Engeriser, J.L., Hutch, T., Smith, C.L. et al. Buprenorphine initiation from fentanyl using low-dose intramuscular ketamine: a pilot study. Addict Sci Clin Pract 21, 23 (2026). https://doi.org/10.1186/s13722-026-00649-3

Abstract

Background

Buprenorphine is an effective medication for treating opioid use disorder but is underutilized partly due to patient apprehensiveness of the severe withdrawal symptoms it can induce when started, particularly by fentanyl-dependent individuals. An emerging facilitator to buprenorphine initiation is ketamine, a dissociative anesthetic shown to reverse opioid withdrawal symptoms in case reports and small series. A 24-hour behavioral health crisis center implemented a quality improvement protocol to address difficulties transitioning patients from fentanyl to buprenorphine using a high-dose buprenorphine initiation strategy premedicated with a low, sub-dissociative dose of intramuscular ketamine.

Methods

Crisis center personnel injected ketamine 10 mg intramuscularly at a cost of $0.44 per patient and 30 minutes later administered buprenorphine 8 mg sublingually to patients who self-reported recent use of fentanyl and were in at least moderate withdrawal. They assessed Clinical Opiate Withdrawal Scale (COWS) scores at baseline, 30 minutes after ketamine, and 30 minutes after buprenorphine. They compared length of stay (LOS) between patients initiating buprenorphine before and after implementing the protocol. They recorded pharmacy dispensing of buprenorphine prescriptions and follow-up visits within 30 days.

Results

In 50 patients treated over 13 months, average COWS score dropped from 13.6 (range 8–21, SD 2.9) at baseline to 6.2 (range 0–17, SD 3.6) 30 minutes after ketamine and 4.1 (range 0–18, SD 4.0) 30 minutes after buprenorphine. Both decreases were statistically significant (p < 0.001) with very large effect sizes. Of the 50 patients, 36 (72%) experienced a decrease in COWS score including 27/50 (54%) with COWS score 0–3 by 30 minutes after buprenorphine. After protocol implementation, median LOS decreased from 66.0 hours (range 20–135) in the pre-protocol comparison sample to 7.0 hours (range 2–148) in the post-protocol sample. Patients reported no adverse effects of ketamine.

Conclusions

In this observational study, sub-dissociative dose intramuscular ketamine was a well-tolerated and inexpensive premedication for a high-dose buprenorphine initiation strategy. Most patients had rapid reduction in signs of fentanyl withdrawal after ketamine, and half had nearly complete resolution following buprenorphine. Ketamine may be a useful adjunct to increase buprenorphine uptake and reduce overdose deaths. Prospective research is warranted.

Key Findings

A) Average COWS scores at baseline, 30 minutes after ketamine, and 30 minutes after buprenorphine were 13.6, 6.2, and 4.1 respectively.

B) 30 minutes after buprenorphine (1 hour after starting the protocol), 49/50 patients (98%) had a lower COWS score, and 54% had COWS score 0–3 (minimal to no withdrawal). 3 patients required overnight stay due to inadequate control of withdrawal.

C) Median length of stay (in hours) at the facility decreased from 66.0 to 7.0 after starting the protocol.