Note: This post was authored by Dr. Raymond Cho in collaboration with Dr. Jessica Moe.

Introduction

The opioid epidemic is a growing healthcare crisis that has claimed over 67,000 lives in the United States in 2018.^1,2 Public health data has shown that ED visits are common in patients who later overdose and therefore, these encounters are critical opportunities to initiate preventative interventions.³ Buprenorphine is a first-line opioid agonist therapy that has been shown not only to reduce illicit opioid use at 30 days but also to be safe in take-home regimens due to its ceiling effect on respiratory depression.^4-6

Buprenorphine is a high-affinity partial agonist for opioid receptors which outcompetes heroin, morphine and other lower-affinity opioids.⁵ This characteristic means that it may induce precipitated withdrawal if introduced in an opioid-dependent patient who has recently ingested other opioids and thus, patients must be in moderate withdrawal before initiating standard doses of buprenorphine. As withdrawal is extremely uncomfortable for patients, this is a major barrier to initiation that causes higher dropout rates.⁷  Microdosing is a novel approach that avoids this need for withdrawal by using small initial doses that increase incrementally over a longer period (generally 6-7 days) while patients continue to take overlapping opioids.⁸

The purpose of this study was to evaluate the feasibility of an ED-initiated buprenorphine/naloxone program that offers standard dosing and microdosing take-home packages, and to assess the feasibility of randomization to these interventions.

Methods

Patients with opioid-use disorder who presented to the emergency department were identified, offered take-home buprenorphine/naloxone packages and enrolled in the study.

These patients were allocated microdosing or standard dosing buprenorphine/naloxone first by convenience sample, then by randomization (please refer to the linked publication below for dosing protocols).

Follow-up was attempted post-ED visit at 7 days via telephone and 30 days in-person by our ED social worker or outreach worker.

Results

Recruitment

94 patients screened positive for opioid-use disorder from July 2019 to March 2020 and 68 (72.3%) were enrolled into the study.
10 patients declined due to poor previous experiences with buprenorphine, of whom 5 specifically cited a fear of precipitated withdrawal.
No patients declined enrollment due to randomization.

14/52 patients (26.9%) of consented patients left against medical advice (AMA) before receiving their buprenorphine/naloxone package. Time stamp data showed that urine toxicology testing was a common rate-limiting step that rarely changed management; no patients left AMA after elimination of this step.

Follow-up

Follow-up was low (9/46 [19.6%] at 7 days and 15/46 [32.6%] at 30 days), making it difficult to determine treatment retention.
Standard dosing: 21 patients were enrolled into standard dosing. At least 5/21 (23.8%) patients remained on opioid agonist therapy at 30-day follow up.
Microdosing: 25 patients were enrolled into microdosing. At least 8/25 (32.0%) patients remained on opioid agonist therapy at 30-day follow up.

Discussion

ED-initiated take-home buprenorphine/naloxone programs that offer standard dosing and microdosing are feasible.
Randomization is not a deterrent to enrollment and is acceptable to our target study population.
Additional lessons from this feasibility study

Most patients with opioid-use disorder presented for reasons unrelated to substance use, indicating a need for broader screening criteria.
Eliminating urine toxicology as a prerequisite for buprenorphine/naloxone may decrease the number of patients who left against medical advice.
Challenges in follow-up suggests a need to engage patients and identify more effective methods of ascertaining patient outcomes in future studies.

Bottom Line

A randomized control trial comparing standard dosing and microdosing buprenorphine/naloxone in the emergency department is feasible.

Source Publication
Microdosing and standard‐dosing take‐home buprenorphine from the emergency department: A feasibility study. (JACEP Open 2020 Oct)
Jessica Moe MD, MSc, Katherin Badke PharmD, BScPharm, Megan Pratt MSW,RSW, Raymond Y Cho MD, Pouya Azar MD, Heather Flemming MD, K. Anne Sutherland MD, MSc, Barbara Harvey MScN, JD, Lara Gurney MSN, RN, Julie Lockington MN, RN, Penny Brasher PhD, Sam Gill RN, BScN, Emma Garrod MSN, RN, Misty Bath MScPH, BSN, Andy Kestler MD, MScPH

Please see https://doi.org/10.1002/emp2.12289 for the full publication.

References

1. Centers for Disease Control and Prevention. Opioid Overdose. 2020; Available from: https://www.cdc.gov/drugoverdose/. [cited October 29, 2020].

2. Woolf SH, Schoomaker H. Life expectancy and mortality rates in the United States, 1959-2017. JAMA 2019 Nov 26;322(20):1996-2016.

3. Otterstatter MC, Crabtree A, Dobrer S, Kinniburgh B, Klar S, Leamon A, et al. Patterns of health care utilization among people who overdosed from illegal drugs: A descriptive analysis using the BC provincial overdose cohort. Health promotion and chronic disease prevention in Canada : research, policy and practice 2018 Sep;38(9):328-338.

4. D’Onofrio G, O’Connor PG, Pantalon MV, Chawarski MC, Busch SH, Owens PH, et al. Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: A randomized clinical trial. JAMA 2015 Apr 28,;313(16):1636.

5. American Society of Addiction Medicine. The ASAM national practice guideline for the treatment of opioid use disorder: 2020 focused update. 2020.

6. Marteau D, McDonald R, Patel K. The relative risk of fatal poisoning by methadone or buprenorphine within the wider population of England and Wales. BMJ Open 2015 May;5(5):e007629.

7. Mattick RP, Ali R, White JM, O’Brien S, Wolk S, Danz C. Buprenorphine versus methadone maintenance therapy: A randomized double-blind trial with 405 opioid-dependent patients. Addiction 2003 Apr;98(4):441-452.

8. Hämmig R, Kemter A, Strasser J, von Bardeleben U, Gugger B, Walter M, et al. Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: The Bernese method. Substance abuse and rehabilitation 2016;7:99-105.