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Three Part Question

In the [Emergency Department patients with opioid use disorder] who are [initiated on buprenorphine therapy during the ED visit] what [proportion of patients can be expected to adhere to buprenorphine treatment long-term]?

Clinical Scenario

A 42 year old male presents to the ED with opioid withdrawal symptoms of moderate severity. He is hoping to be prescribed opioid agonist therapy treatment with buprenorphine. He has no other complaints.

Search Strategy

Ovid MEDLINE(R) and Epub Ahead of Print, In-Process, In-Data-Review & Other Non-Indexed Citations and Daily <1946 to February 13, 2023>
[exp Buprenorphine, Naloxone Drug Combination/ or exp Buprenorphine/ or buprenorphine.mp. OR suboxone.mp. or exp Buprenorphine, Naloxone Drug Combination or exp Buprenorphine/ or exp Opiate Substitution Treatment/ or opioid agonist therapy.mp.] AND [exp emergency department.mp. or exp Emergency Service, Hospital/ or emergency medicine.mp. or exp Emergency Medicine/ or acute care.mp. or accident and emergency.mp. or a&e.mp.]

Search Outcome

The initial literature search yielded 371 papers. 360 papers were excluded during the initial title and abstract review. Out of the 11 papers selected for full paper review, 1 was excluded due the inclusion of patients from outside the Emergency Department. Another paper was discovered to be a partial dataset of a different article already included in the full paper review so these 2 studies were merged.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Bogan C. et al. 2020 USA	231 patients who received sublingual buprenorphine or buprenorphine/naloxone in the ED.	Prospective cohort study within an implementation study.	Number of patients retained in treatment at 30 days.	46% (111/231) of patients whose treatment was initiated in the ED adhered to treatment.	Observational study. There is no data about patients who may have switched to other opioid agonist therapy medications. Some patients may have continued with buprenorphine treatment without engaging in the ongoing community treatment and their outcomes would not have been captured by this study.
D'Onofrio G. et al. 2017 USA	329 ED patients underwent initial randomization into one of three treatment arms: buprenorphine/naloxone, brief intervention, or referral. 92 ED patients with moderate to severe opioid withdrawal symptoms were initiated on buprenorphine/naloxone treatment with a plan for 10-week treatment continuation in primary care. All patients received sufficient take-home daily doses to ensure adequate medication until a follow-up appointment.	Randomized controlled trial.	Engagement in formal addiction treatment at 2 months.	74%(68/92) of patients in the buprenorphine group were adherent to treatment vs 53%(42/79) in the referral group and 47%(39/83) in the brief intervention group.	The initial study only provided buprenorphine treatment through an outpatient program for the first 10 weeks. After this point, patients either had to find other pathways to ongoing treatment, switch to alternative medications or go through a tapering process. The ED and the primary-care treatment center for the buprenorphine group were located in the same institution making results less generalizable to locations where outpatient follow-up may be in a different institution. 22 patients were lost to follow-up at 2 and 6 months and 28 patients at 12 months. The authors reported adherence as a proportion of patients they were able to follow-up with, which in turn may have over or underestimated the results at different time points.
			Engagement in formal addiction treatment at 6 months.	53%(49/92) of patients in the buprenorphine group were adherent to treatment vs 60%(42/70) in the referral group and 51%(39/76) in the brief intervention group.
			Engagement in formal addiction treatment at 12 months.	49%(42/86) of patients in the buprenorphine group were adherent to treatment vs 49%(36/73) in the referral group and 63%(49/78) in the brief intervention group.
Hu T. et al. 2019 Canada	43 patients in mild to moderate opioid withdrawal who underwent buprenorphine/naloxone treatment initiation in the ED. These patients then received a prescription with up to three daily observed doses and a referral was sent to the rapid access addiction clinic.	Prospective cohort study.	Ongoing buprenorphine/naloxone treatment 6 months after the index ED visit. Adherence was confirmed with treatment providers.	35%(15/43) patients were adherent to medication.	Small sample size. This study excluded patients who used opioids within the previous 12 hours and required patients to be in mild to moderate withdrawal without an option for home-induction. The study also excluded patients who consented to receive buprenorphine/naloxone treatment but did not consent to a referral. 47 % (20/43) of patients did not attend the initial appointment.
Kaucher K et al. 2019 USA	219 patients who underwent a buprenorphine induction in the ED. All patients received an outpatient referral for next-day appointment with a medication assisted therapy (MAT) provider. If no next-day appointments were available, patients were given a buprenorphine/naloxone prescription.	Prospective cohort study.	Engagement in MAT at 30 days, including patients who transitioned to methadone treatment.	49%(108/219) of patients were adherent to MAT.	Single center study. 26%(57/219) of the initial cohort were discharged from the MAT clinic because they did not attend the initial appointment, 14%(15/219) due to relocation/incarceration and 6%(7/219) due to lack of transportation or clinic hours. Some of these discharged patients may have continued with treatment however their outcomes would not have been included in the final analysis.
Krenz J. et al. 2022 USA	155 patients who were initiated on buprenorphine therapy in the ED, with 35 patients who received the first medication dose in the ED and 120 patients who followed a home-induction protocol. All patients were discharged with a three-day medication supply and instructions to follow-up on the same or next day at the institution’s outpatient clinic.	Retrospective cohort study.	The proportion of patients who filled a prescription for buprenorphine 3 months after index ED visit according to the pharmacy records.	45.2%(70/155) of patients filled buprenorphine prescription.	Some of the patients who did not fill buprenorphine prescriptions at the established time points may have transitioned to methadone treatment instead and their outcomes would not have been captured by this study. Prescription filling may not be indicative of medication adherence.
			The proportion of patients who filled a prescription for buprenorphine 6 months after index ED visit according to the pharmacy records.	41.3%(64/155) of patients filled buprenorphine prescription.
McLane P. et al. 2020 Canada	47 ED patients who were discharged on buprenorphine/naloxone treatment either following an ED induction or with a plan for home induction. The comparison group included 335 ED patients with opioid-related ED visits who did not receive buprenorphine-naloxone treatment.	Case-control study within a quality improvement study.	Number of patients filling any opioid agonist treatment prescription 30 days after ED discharge.	74.4%(35/47) of patients in the intervention group filled an opioid agonist treatment in comparison with 33.4%(112/335) of patients in the control group.	No statistical analysis for significance. The final outcome measures include patients who were taking any opioid agonist treatment and not just buprenorphine. There are no details regarding the intervention itself, such as the initial medication dosing.
			Number of patients filling any opioid agonist treatment prescription 60 days after ED discharge.	74.4%(35/47) of patients in the intervention group filled an opioid agonist treatment prescription in comparison with 32.8%(110/335) of patients in the control group.
			Number of patients filling any opioid agonist treatment(OAT) prescription 30, 60, 90 days after ED discharge.	72.3%(34/47) of patients in the intervention group filled an opioid agonist treatment prescription in comparison with 32.5%(109/335) of patients in the control group.
Moe J et al. 2020 Canada	68 patients were enrolled initially, however, 14 left against medical advice, and 8 were excluded prior to treatment initiation so a total of 46 patients were included in the final study cohort. 21 patients underwent a standard protocol for buprenorphine initiation whereas 25 patients underwent a microdosing protocol.	Mixed study design.	Opioid agonist therapy adherence 30 days after the index ED visit.	23.8%(5/21) of patients who received standard dosing and 32% (8/25) of patients who received microdosing remained on opioid agonist therapy.	Many patients lost to follow-up. Reliance on self-reporting. Small sample size.
Reuter Q. et al. 2022 USA	279 patients enrolled in the ED medication for opioid use disorder(MOUD) Program.	Prospective cohort study.	Treatment retention(defined as adherence to buprenorphine/naloxone) at 1 month after the initial ED visit.	54.1%(151/279) of patients adherent to treatment.	Prescription monitoring program was used to monitor adherence, however, there was no way to confirm whether patients were truly taking the medication. This method of monitoring also would not include patients who may be receiving treatment through in-patient and day programs.
			Treatment retention(defined as adherence to buprenorphine/naloxone) at 3 months after the initial ED visit.	43.0%(120/279) of patients adherent to treatment.
			Treatment retention(defined as adherence to buprenorphine/naloxone) at 6 months after the initial ED visit.	37.6%(105/279) of patients adherent to treatment.
			Treatment retention(defined as adherence to buprenorphine/naloxone) at 12 months after the initial ED visit.	34.8%(97/279) of patients adherent to treatment.
Srivastava et al. 2019 Canada	26 ED patients with opioid withdrawal symptoms were randomized to receive buprenorphine or clonidine.	Randomized controlled trial.	Adherence to opioid agonist therapy(OAT) at 1 month.	62%(8/13) of patients randomized to buprenorphine arm were adherent to OAT treatment in comparison with 8%(1/13) in the clonidine arm.	Small sample size. Unequal numbers of patients lost to follow-up(6 in the clonidine group and 3 in the buprenorphine group). Unclear whether all patients adherent to OAT were still on buprenorphine or switched to a different medication prior to the 30-day follow-up.

Comment(s)

There is weak to moderate evidence that buprenorphine initiation in the ED leads to opioid agonist treatment retention rates of 25-50% thirty days after the initial visit. Most of the studies included in this review were cohort studies with 1 of the randomized controlled trials having a very small sample size. The desired outcome of adherence can also be challenging to assess given the varied practices accessing pharmaceutical dispensing information and social factors related to the populations in which substances use issues are more prevalent. The proportion of patients adherent to treatment after 30 days is challenging to estimate due to losses to follow-up, switches to other medications or completion of treatment, however some of the studies report adherence rates of 30-70% at 3 and 6 months after medication initiation.

Clinical Bottom Line

Initiation of opioid agonist treatment with buprenorphine in the ED can lead to long-term treatment adherence in up to half of the patients.

References

1. Carolyn Bogan, Lindsey Jennings, Louise Haynes, Kelly Barth, Angela Moreland, Marla Oros, Sara Goldsby, Suzanne Lane, Chanda Funcell, Kathleen Brady Implementation of emergency department-initiated buprenorphine for opioid use disorder in a rural southern state Journal of Substance Abuse Treatment 2020
2. Gail D'Onofrio, Marek C Chawarski, Patrick G O'Connor, Michael V Pantalon, Susan H Busch, Patricia H Owens, Kathryn Hawk, Steven L Bernstein, David A Fiellin Emergency Department-Initiated Buprenorphine for Opioid Dependence with Continuation in Primary Care: outcomes During and After Intervention Journal of General Internal Medicine 2017
3. Tina Hu, Melissa Snider-Adler, Larry Nijmeh and Adam Pyle Buprenorphine/naloxone induction in a Canadian emergency department with rapid access to community-based addictions providers Canadian Journal of Emergency Medicine 2019
4. Kevin A Kaucher, Emily H Caruso, Gannon Sungar, Lisa Gawenus, Katherine Hurlbut, Dayan Colon Sanchez and Kerry Broderick Evaluation of an emergency department buprenorphine induction and medication-assisted treatment referral program American Journal of Emergency Medicine 2019
5. James R. Krenz, Bryan D. Hayes, Sarah E. Wakeman, Alister Martin, Ali S.Raja, Benjamin A. White and Jennifer L. Koehl Continuation of outpatient buprenorphine therapy after dispensing Buprenorphine-Naloxone from the emergency department Clinical Toxicology 2022
6. Patrick McLane, Ken Scott, Zainab Suleman, Karen Yee, Brian R Holroyd, Kathryn Dong, S Monty Ghosh, Josh Fanaeian, Jan Deol, Catherine Biggs and Eddy Lang Multi-site intervention to improve emergency department care for patients who live with opioid use disorder: A quantitative evaluation Canadian Journal of Emergency Medicine 2020
7. Jessica Moe, Katherin Badke, Megan Pratt, Raymond Y Cho, Pouya Azar, Heather Flemming, K Anne Sutherland, Barbara Harvey, Lara Gurney, Julie Lockington, Penny Brasher, Sam Gill, Emma Garrod, Misty Bat Microdosing and standard-dosing take-home buprenorphine from the emergency department: A feasibility study Journal of the American College of Emergency Physicians Open 2020
8. Quentin R. Reuter, Amanda Dos Santos, Jamie McKinnon, David Gothard, Nicholas Jouriles and David Seaberg Long-term treatment retention of an emergency department initiated medication for opioid use disorder program American Journal of Emergency Medicine 2022
9. Anita Srivastava, Meldon Kahan, Irene Njoroge, Leeor Z. Sommer Buprenorphine in the emergency department: Randomized clinical controlled trial of clonidine versus buprenorphine for the treatment of opioid withdrawal Canadian Family Physician 2019