ED-Initiated Medication for Addiction Therapy

Case presentation:

55 year-old man with a past medical history of hypertension and intravenous drug use presents to the Emergency Department at night with two weeks of upper back pain.

· Clinical evaluation and imaging show no evidence of paraspinal/epidural abscess or other emergent back pain etiologies. Notable symptomatic improvement with topical anesthetics and NSAIDS.

· The patient reports a 15-year history of intravenous drug use (heroin and fentanyl). He reports last using fentanyl 8 hours prior to presentation. Denies use of illicit drugs other than opioids.

· He reports a prior successful three-year period of methadone maintenance treatment during which he abstained from illicit drug use.

· The patient expresses a desire to reinitiate medication for addiction therapy (MAT) as soon as possible. He is advised to return to the ED the following morning to speak to a peer recovery specialist. However, following discharge, he does not return to the ED.

Clinical question:

What is the evidence for medication for addiction therapy (MAT), and specifically ED-initiated MAT, and what issues should be addressed when considering its use?

What is the evidence for ED-initiated MAT?

· Outpatient MAT. Observational study (2011): Outpatients with opioid use disorder not receiving MAT had 75% higher overall mortality over 6 months than those receiving buprenorphine-based MAT.1

o Cochrane metanalysis (2014): Across 13 trials, fixed-dose buprenorphine was as effective as methadone in retaining participants in outpatient MAT and reducing illicit opioid use.2

· RCT (2015): ED patients randomized to receive buprenorphine MAT + motivational counseling + outpatient referral (n=114) were more likely to be engaged in addiction treatment at 30 and 60 days post-randomization than those randomized to referral alone or referral + counseling (n=213; 78% vs. 41% [pooled control group] at 30 days3; 74% vs. 50% at 60 days4).

o Caveat: No difference in treatment engagement at 6 months or 12 months post-randomization.4

· Single-site observational study (2020): In a programmatic setting, 74% of patients started on buprenorphine in the ED presented for outpatient MAT and 49% were still in treatment at 30 days.5

· Cost-effectiveness analysis (2018): ED-initiated MAT costs $8-$83 per patient and is cost-saving to both the health system and the patient. ED-initiated MAT is more cost effective than simple outpatient MAT referral with fewer hospital admissions, shorter clinic visits, and higher retention in care.6

o Caveat: Based on the 30-day results of the RCT above. Real-world cost-effectiveness is likely to depend on long-term retention in care.

· Multi-site urban study (2020): Significant barriers to ED-initiated MAT remain. Only 21% of ED providers self-reported being ready to initiate MAT. Many reported lack of training, competing priorities, and concerns about linkage to care.7

How does ED-initiated MAT work?

· Screening and referral to MAT: Patients presenting for care are screened for nonmedical use of opioids. Patient with opioid use disorder or presenting with withdrawal symptoms are approached for motivational counseling and to assess interest in MAT.

· ED-initiated treatment:

o Agent: Buprenorphine/naloxone – buprenorphine, a high-affinity partial opioid receptor agonist + naloxone, an opioid antagonist with poor oral bioavailability to deter IV use.

o Protocol: A score of ≥8 on the Clinical Opiate Withdrawal Scale (COWS) is recommended before starting buprenorphine. The COWS includes assessment of heart rate, diaphoresis, rhinorrhea, restlessness, anxiety, tremor, GI upset, pupil size, myalgias, yawning and piloerection. Dosing: initial ED dose of 4-8 mg sublingual buprenorphine, with further doses every 1-2 hours to achieve symptomatic relief.

· Prescription and outpatient referral: Once relief from withdrawal is achieved or if not in active withdrawal, the patient should be discharged with close referral to outpatient MAT, a prescription for buprenorphine to last through linkage to outpatient MAT (~3 days), and instructions on buprenorphine use.

What are the risks in prescribing buprenorphine?

· Withdrawal: Buprenorphine can displace other opioids and precipitate withdrawal. To avoid this, ensure that sufficient time has passed since last opioid use (COWS ≥8). If precipitated withdrawal occurs, treat with further buprenorphine doses (2-4 mg/hr or 0.3 mg IV/IM every 30 mins) until symptoms resolve.

What are the legal and regulatory concerns in prescribing buprenorphine?

· All physicians with the ability to prescribe opioids can prescribe buprenorphine to patients experiencing withdrawal while in the hospital/clinic, for up to 72 hours.

· To write a prescriptions for buprenorphine at discharge, providers must apply for a DATA 2000 waiver (an “X waiver”). Physicians must undergo an 8-hour training to obtain the waiver and are limited to treating 30 patients concurrently with buprenorphine in the first year.

· Up to 70% of Medicaid plans require prior authorization for buprenorphine.8

Conclusions and Recommendations

· ED-initiated buprenorphine protocols appear safe, efficacious, and cost-effective in facilitating short-term engagement in MAT.

· Further research is needed to understand the longer-term impact of ED-initiated treatment. However, even short term MAT engagement may reduce the risk of overdose and secondary harms.

· ED-initiated MAT is not simply a pharmacologic intervention. Successful implementation requires organizational and systemic buy-in, including resources for training, ED-based counseling, and close coordination with outpatient MAT providers.

· Broader uptake of ED-based MAT will require increased resources and support for X-waiver training, and wider availability of outpatient MAT clinics

References

1.Clark RE, Samnaliev M, Baxter JD, Leung GY. The evidence doesn't justify steps by state Medicaid programs to restrict opioid addiction treatment with buprenorphine. Health Aff (Millwood). Aug 2011;30(8):1425-33.

2.Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. Feb 2014;(2):CD002207.

3.D'Onofrio G, O'Connor PG, Pantalon MV, et al. Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial. JAMA. Apr 2015;313(16):1636-44.

4.D'Onofrio G, Chawarski MC, O'Connor PG, et al. Emergency Department-Initiated Buprenorphine for Opioid Dependence with Continuation in Primary Care: Outcomes During and After Intervention. J Gen Intern Med. Jun 2017;32(6):660-666.

5.Kaucher KA, Caruso EH, Sungar G, et al. Evaluation of an emergency department buprenorphine induction and medication-assisted treatment referral program. Am J Emerg Med. 02 2020;38(2):300-304.

6.Busch SH, Fiellin DA, Chawarski MC, et al. Cost-effectiveness of emergency department-initiated treatment for opioid dependence. Addiction. Nov 2017;112(11):2002-2010.

7.Hawk KF, D'Onofrio G, Chawarski MC, et al. Barriers and Facilitators to Clinician Readiness to Provide Emergency Department-Initiated Buprenorphine. JAMA Netw Open. May 2020;3(5):e204561.

8.Andrews CM, Grogan CM, Smith BT, et al. Medicaid Benefits For Addiction Treatment Expanded After Implementation Of The Affordable Care Act. Health Aff (Millwood). 08 2018;37(8):1216-1222. doi:10.1377/hlthaff.2018.0272