Buprenorphine Treatment of Opioid Use Disorder for Individuals Using High-potency Synthetic Opioids

Publication Date: July 28, 2023
Last Updated: November 14, 2024

Summary of Key Questions and Clinical Considerations

What Specific Clinical Situations Favor Use of Low- or High-Dose Buprenorphine Initiation Strategies?

  • Observational data suggest buprenorphine initiation is best individualized by setting and patient preference.
  • LDB-OC in hospital settings appears to be well tolerated in observational data.
  • More evidence is needed to determine the optimal strategy for LDB-OC in ambulatory settings for patients who are ineligible for medically prescribed FAO under current regulations.
  • In patients with chronic exposure to HPSO who initiate buprenorphine after opioid abstinence and development of OWS, rapid dose escalation has been observed to be safe, primarily in the ED setting.

What Strategies Can Address Patient Discomfort, Including Precipitated Opioid Withdrawal, If It Occurs During Buprenorphine Initiation?

  • For mild to moderate OWS during buprenorphine initiation, treatment with buprenorphine >24 mg SL on day 1 may be considered for patients with clinically apparent high opioid tolerance.
  • For mild to moderate OWS during buprenorphine initiation, alpha-2 agonists and other symptom-targeted treatments may be helpful in addition to more buprenorphine.
  • For intractable cases of OWS, treatment escalation involves transition to an ED or hospital for additional buprenorphine and consideration of high-affinity FAO, benzodiazepines, ketamine, or dexmedetomidine.

After Buprenorphine Initiation, What Range of Buprenorphine Dosing and/or Dosing Strategies Can Be Considered During Stabilization and Long-Term Treatment?

  • Some patients with high opioid tolerance may require buprenorphine doses >24 mg/d during treatment stabilization.
  • Physiological changes during pregnancy alter buprenorphine metabolism, necessitating adjusted buprenorphine dose and dosing intervals.
  • Consider dose and frequency adjustments, psychosocial supports, and a higher level of care if individuals are unable to stabilize with buprenorphine.
  • Consider a reassessment of higher (>24 mg/d) long-term doses once patients enter long-term treatment without ongoing use of opioids.

What Are Indications for Injectable Extended-Release Buprenorphine for OUD Treatment Compared With Sublingual Formulations?

  • Consider XR buprenorphine formulations for individuals unable to stabilize on SL buprenorphine formulations, particularly individuals who have had extensive HPSO exposure, unsafe living environments, and/or multiple opioid overdoses.
  • Consider the administration of XR buprenorphine soon after successful buprenorphine initiation to achieve durable opioid overdose protection.
  • Although XR buprenorphine is reaching steady state, consider the risks and benefits of additional SL buprenorphine, particularly for pregnant individuals.

How Do Other Novel Drug Components Affect Buprenorphine Initiation and Stabilization?

  • Consider withdrawal from other substances when OWS does not respond as expected to ancillary medications and buprenorphine; utilize a higher level of care as needed.
  • Consider other etiologies or overdose from other substances when an individual does not respond as expected to multiples doses of naloxone.
  • Consider using comprehensive toxicology testing and drug checking to identify drug components; use this information to inform harm reduction and overdose prevention strategies.

What Are OUD Treatment Alternatives After Repeated Unsuccessful Attempts at Buprenorphine Treatment?

  • If a patient has been unsuccessful with buprenorphine initiation and continues desiring buprenorphine, consider a higher level of care and/or alternative initiation strategies.
  • Consider methadone for individuals who are unable to stabilize safely and effectively on buprenorphine.
  • Consider XR naltrexone initiation only in individuals in a highly structured, medically managed inpatient environment.

Table 2 - Clinical Decision Support for Buprenorphine Initiation Techniques Based on the Clinical Setting

Having trouble viewing table?
Fastest Slowest
Initiation Strategy* HDB† Standard‡ LDB-OC§
Possible advantages Quick stabilization
Bridge access barriers to ongoing buprenorphine		 -Most common and well-described technique -Opioid abstinence not initially required
Need for opioid withdrawal? Yes Yes No
Premedicate with adjuvant medications?∥ Consider Yes Yes
Initial starting dose¶ (buprenorphine SL formulation) 8–16+ mg 2–8 mg 0.25 mg–1 mg
Duration of initiation until stabilization ≤2 h 1–3 days 3–10 d (may be longer in certain situations)
Need for opioid continuation No No Yes
Full agonist opioid continuation dose None None Examples: Methadone 30 mg PO daily OR Hydromorphone 4 mg PO every 4 hr OR Self-directed illicit/nonprescribed opioid use
Care coordination required Moderate Moderate High

*See Appendix C (https://links.lww.com/JAM/A431) for example protocols of these strategies.
†HDB = high-dose buprenorphine; this is sometimes referred to as “macrodosing.”
‡Standard buprenorphine initiation is based on the ASAM NPG and typically occurs with medically managed instructions for home buprenorphine initiation.3
§LDB-OC = low-dose buprenorphine with opioid continuation; this is sometimes referred to as “microdosing” or “microinduction” but the most clinically accurate term is used here.
∥Adjuvant medications include clonidine, hydroxyzine, acetaminophen, and NSAIDs (Appendix D, https://links.lww.com/JAM/A431).
¶This refers to the initial dose only. The total daily dose on day 1 and subsequent days is likely more than this initial dose.

Table 3 - Considerations for Buprenorphine Initiation Approach Based on High-Tolerance and High-Potency Synthetic Opioid Exposure—Clinical Setting and Opioid Withdrawal

Having trouble viewing table?
Situation Outpatient Emergency Department Residential/Hospital Setting*
Opioid withdrawal, COWS ≥8 with 1 objective sign of opioid withdrawal Standard initiation or HDB Standard initiation or HDB Standard initiation or HDB
Opioid withdrawal, COWS <8 Standard initiation or LDB-OC† Standard initiation or LDB-OC† Standard initiation or LDB-OC†
Pain + opioid withdrawal, COWS <8 Standard initiation or prescribed FAO for pain with LDB-OC Standard initiation or prescribed FAO for pain with LBD-OC Administered FAO + LDB-OC
*Includes medically managed levels of care such as ASAM 4th Edition Levels of Care 3.7 (medically managed rehab), 4.0 (hospital setting).
†LDB-OC = low-dose buprenorphine initiation with opioid continuation (prescribed versus nonprescribed). Requires an individualized determination of the risks and benefits of prescribed full opioid agonist within federal regulations versus continuation of an illicitly obtained full opioid agonist.

Recommendation Grading

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Buprenorphine Treatment of Opioid Use Disorder for Individuals Using High-potency Synthetic Opioids

Authoring Organization

American Society of Addiction Medicine

Publication Month/Year

July 28, 2023

Last Updated Month/Year

November 14, 2024

Document Type

Consensus

Country of Publication

US

Document Objectives

Treatment of opioid use disorder (OUD) with buprenorphine has evolved considerably in the last decade as the scale of the OUD epidemic has increased along with the emergence of high-potency synthetic opioids (HPSOs) and stimulants in the drug supply. These changes have outpaced the development of prospective research, so a clinical consideration document based on expert consensus is needed to address pressing clinical questions. This clinical considerations document is based on a narrative literature review and expert consensus and will specifically address considerations for changes to the clinical practice of treatment of OUD with buprenorphine for individuals using HPSO. An expert panel developed 6 key questions addressing buprenorphine initiation, stabilization, and long-term treatment for individuals with OUD exposed to HPSO in various treatment settings. Broadly, the clinical considerations suggest that individualized strategies for buprenorphine initiation may be needed. The experience of opioid withdrawal negatively impacts the success of buprenorphine treatment, and attention to its management before and during buprenorphine initiation should be proactively addressed. Buprenorphine dose and dosing frequency should be individualized based on patients’ treatment needs, the possibility of novel components in the drug supply should be considered during OUD treatment, and all forms of opioid agonist treatment should be offered and considered for patients. Together, these clinical considerations attempt to be responsive to the challenges and opportunities experienced by frontline clinicians using buprenorphine for the treatment of OUD in patients using HPSOs and highlight areas where prospective research is urgently needed.

Target Patient Population

Individuals with severe opioid use disorder chronically exposed to high potency synthetic opioids

Target Provider Population

All providers caring for patients with opioid use disorder

PICO Questions

  1. What Specific Clinical Situations Favor Use of Low- or High-Dose Buprenorphine Initiation Strategies?

  2. What Strategies Can Address Patient Discomfort, Including Precipitated Opioid Withdrawal, If It Occurs During Buprenorphine Initiation?

  3. After Buprenorphine Initiation, What Range of Buprenorphine Dosing and/or Dosing Strategies Can Be Considered During Stabilization and Long-Term Treatment?

  4. What Are Indications for Injectable Extended-Release Buprenorphine for OUD Treatment Compared With Sublingual Formulations?

  5. How Do Other Novel Drug Components Affect Buprenorphine Initiation and Stabilization?

  6. What Are OUD Treatment Alternatives After Repeated Unsuccessful Attempts at Buprenorphine Treatment?

Inclusion Criteria

Male, Female, Adolescent, Adult, Older adult

Health Care Settings

Ambulatory, Emergency care, Outpatient

Intended Users

Addiction treatment specialist, counselor, nurse, nurse practitioner, physician, physician assistant, psychologist

Scope

Treatment, Management, Prevention

Keywords

buprenorphine, Opioid Use Disorder, synthetic opioids, medication assisted treatment

Source Citation

Weimer MB, Herring AA, Kawasaki SS, Meyer M, Kleykamp BA, Ramsey KS. ASAM Clinical Considerations: Buprenorphine Treatment of Opioid Use Disorder for Individuals Using High-potency Synthetic Opioids. J Addict Med. 2023 Nov-Dec 01;17(6):632-639. doi: 10.1097/ADM.0000000000001202. Epub 2023 Jul 28. PMID: 37934520.