Buprenorphine: An Evidence-Based Approach

Educational Objectives

The goal of this program is to improve use of buprenorphine. After hearing and assimilating this program, the clinicians will be able to:

1. Adjust or maintain home dosing of buprenorphine during in-hospital treatment of acute pain.
2. Treat precipitated withdrawal when initiating buprenorphine.
3. Optimize buprenorphine dosing in the management of chronic pain.

Summary

Background: buprenorphine is an opioid used to treat opioid use disorder (OUD) and acute and chronic pain; unlike full agonists (eg, morphine, heroin), buprenorphine is a partial agonist at the mu receptor

Use in treatment of OUD: per the criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, individuals with OUD have impaired control over opioid use, social impairment, use in hazardous situations or despite harm, and tolerance or withdrawal; buprenorphine is useful for OUD because of similar rates of opioid abstinence but better rates of treatment retention compared with methadone, reduced use of other opioids, and lower risk for overdose (plus lowered rate of all-cause mortality) even after discontinuation; compared with no treatment, Sordo et al (2017) demonstrated more significantly decreased all-cause mortality for patients during and after opioid substitution treatment with buprenorphine vs methadone

Formulations: monoproducts only contain buprenorphine; despite initial concerns, research shows minimal misuse, with most instances aligning with therapeutic indications; combination formulations pair buprenorphine with naloxone, which acts as a deterrent against nonoral use of buprenorphine; however, despite some absorption of naloxone (which can create problems for certain patients), this combination is typically considered first-line therapy per various guidelines; injectables are monoproducts, and it is thought that injectables can improve medication adherence and reduce the risk for diversion

Buprenorphine and Management of Acute Pain

Management of buprenorphine for patients undergoing surgery: discontinuing buprenorphine — may seem logical but poses risks for relapse and overdose; additionally, restarting buprenorphine upon discharge requires induction; dose reduction — may benefit patients on higher doses (eg, 32 mg) undergoing major procedures; this frees up some opioid receptors, allowing traditional pain medications to bind; continuing the current dose without reduction — emerging evidence supports the ability to achieve analgesia despite buprenorphine dose; Buresh et al (2020) found that most patients who maintained their home buprenorphine dose during the perioperative setting were able to achieve adequate pain control; a number of major organizations discourage the routine discontinuation of buprenorphine in the perioperative setting

Pain management strategies: consider splitting the dose to provide buprenorphine every 6 to 8 hr, or increasing the dose to ≤32 mg; first explore nonopioid options if buprenorphine alone is inadequate; full mu-receptor agonists may be necessary for moderate to severe pain; a history of OUD does not preclude the use of opioids in the hospital, but patients may require higher opioid doses than individuals who have not previously taken opioids; frequent reassessment, titration, and an individualized approach to discharge planning are important; consider the patient's destination after discharge, expected pain levels, and overall recovery progress

Initiating Buprenorphine

Precipitated withdrawal: occurs secondary to a net decrease in mu opioid receptor activity when buprenorphine (a partial agonist with high binding affinity) displaces a full mu opioid agonist; naloxone does not contribute to precipitated withdrawal; symptoms are the same as with typical withdrawal, begin 1 to 2 hr after giving buprenorphine, and subside over 6 to 24 hr

Management: reassurance and symptomatic medication — prescribe, eg, clonidine, ondansetron to manage symptoms, and provide reassurance that symptoms will resolve with time; prescribe more buprenorphine — most preferable; done with the goal to minimize the duration of active withdrawal; abandon buprenorphine treatment — least preferable; may be requested by a patient with a poor experience with precipitated withdrawal; requires prescription of a full mu-opioid receptor agonist

Induction strategies

Standard: induce withdrawal by reducing or stopping the hydromorphone patient-controlled analgesia (PCA); gradually introduce buprenorphine during mild to moderate withdrawal (Clinical Opiate Withdrawal Scale [COWS] score ≥8), starting with low doses (eg, 2 mg every 2 hr) and titrating up to 8 mg over ≥2 days; this can be done on an inpatient or outpatient basis and with or without naloxone

Microdosing: though not necessary, consider transition from PCA to an oral pain medication and ensure acute pain needs are met before transitioning to buprenorphine; initiate a buprenorphine patch (provides lower doses of buprenorphine than sublingual films), add a 2 mg buprenorphine film, then increase film dosing to the full dose (8 mg/2 mg buprenorphine-naloxone) and discontinue the patch; microdosing takes ≥3 days (longer for patients with significant injuries); microdosing can be done on an inpatient or outpatient basis without the need for a state of withdrawal; some patients need ≤10 days to make the full transition

Macrodosing: discontinue or significantly decrease PCA dosing, then prescribe buprenorphine 4 mg and rapidly escalate doses (over ≈2 hr) with COWS score ≥8; recommended for inpatient setting or in the emergency department, but not an outpatient setting; patients must enter withdrawal; low-dose forms of buprenorphine are not needed

Discharge planning: have social workers and discharge planners coordinate appropriate care outside the hospital for buprenorphine maintenance; provide counseling regarding harm reduction; provide naloxone in hand at discharge, as patients are at increased risk for overdose after a period of opioid abstinence; collaborate with the patient to construct a pain management regimen

Buprenorphine and Chronic Pain

Comprehensive pain management: involves educating patients about pain self-management and self-care; goals include reducing pain, restoring function, cultivating well-being, and improving quality of life; medication modalities — medications include, eg, nonsteroidal anti-inflammatory drugs (NSAIDs), anticonvulsants, antidepressants, topical agents, opioids; physical modalities — include, eg, exercise, manual therapies, acupuncture, orthotics, transcutaneous electrical nerve stimulation, physical therapy; psychobehavioral interventions — include, eg, cognitive-behavioral therapy, acceptance and commitment therapy, treatment for mood or trauma issues or substance use; meditation and mindfulness are evidence-based interventions for chronic pain; procedural modalities — typically offer short-term relief

Setting realistic goals: set realistic expectations while acknowledging the complexity of medical problems and limitations and establishing achievable objectives; rather than referring the patient to someone else, consider the importance of establishing long-term relationships and making incremental adjustments

Multimodal approach to treatment: the 5 pillars of treatment are psychosocial engagement, physical mobility, weight loss, treatment of substance use disorder (SUD), and consideration of other medications; the World Health Organization pain relief ladder underscores the importance of nonopioid options, including topical agents (eg, lidocaine, diclofenac gel, capsaicin cream), acetaminophen, NSAIDs, muscle relaxants, antiseizure medications (useful for neuropathic pain), tricyclic antidepressants (useful for fibromyalgia), selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors

Opioid efficacy: Krebs et al (2018) demonstrated no difference in pain outcomes among patients taking nonopioid vs opioid pain medications for management of chronic hip or back pain; functional response was achieved by 60% of patients in both groups; patients taking opioid medications more commonly experienced adverse effects than patients taking nonopioid medications

Prescription pearls: active tobacco use disorder is a risk factor for misuse of full mu-agonist opioids; for individuals with complex medical histories and a history of SUD, consider buprenorphine for management of severe, chronic pain if other treatment options are considered inadequate; the buprenorphine transdermal patch is changed weekly and provides 5 to 20 μg/hr (the highest dose provides ≈25% of the strength of the lowest dose of buprenorphine prescribed for addiction); the dissolvable buccal film is taken 2 to 3 times a day and provides 75 to 900 μg/dose; buprenorphine/naloxone products have been used off-label for pain, particularly when patients also have OUD; because of its shorter-acting analgesic impact, split dosing is used for optimal results

Readings

Anderson C, Cooley R, Patil D. Transitioning from high-dose methadone to buprenorphine using a microdosing approach: unique considerations at ASAM level 3 facilities. J Addict Med. 2023;17:241-244. doi:10.1097/ADM.0000000000001085. View article; Azar P, Wong JS, Mathew N, et al. 48-hour induction of transdermal buprenorphine to extended-release buprenorphine. J Addict Med. 2023:10-97. doi:10.1097/ADM.0000000000001231. View article; Davis MP, Behm B, Fernandez C. Buprenorphine. BMJ Support & Palliat Care. 2023.13:125-126. doi:10.1136/spcare-2022-003954. View article; Gregg J, Hartley J, Lawrence D, et al. The naloxone component of buprenorphine/naloxone: discouraging misuse, but at what cost?. J Addict Med. 2023;17:7-9. doi:10.1097/ADM.0000000000001231. View article; Kornfeld H, Reetz H. Transdermal buprenorphine, opioid rotation to sublingual buprenorphine, and the avoidance of precipitated withdrawal: a review of the literature and demonstration in three chronic pain patients treated with butrans. Am J Therapeutics. 2015;22:199-205. doi:10.1097/MJT.0b013e31828bfb6e. View article; Krebs EE, Gravely A, Nugent S, et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: the SPACE randomized clinical trial. JAMA. 2018;319(9):872-882. doi:10.1001/jama.2018.0899. View article; Quaye A, Zhang Y. Perioperative management of buprenorphine: solving the conundrum. Pain Med. 2019;20(7):1395-1408. doi:10.1093/pm/pny217. View article; Sordo L, Barrio G, Bravo M, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017;357:j1550. doi:10.1136/bmj.j1550. View article; Weimer MB, Herring AA, Kawasaki SS, et al. ASAM Clinical Considerations: buprenorphine treatment of opioid use disorder for individuals using high-potency synthetic opioids. J Addict Med. 2023;17(6):632-639. doi:10.1097/ADM.0000000000001202. View article.

Disclosures

For this program, faculty and the members of the planning committee reported nothing relevant to disclose. Dr. Thacker and Dr. Liebschutz presented information that is related to off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Thacker and Dr. Liebschutz were recorded at Update in Internal Medicine: Advances Changing Practice, held virtually October 19-20, 2023, and presented by the University of Pittsburgh School of Medicine. For more information about the upcoming CME activities from this presenter, please visit https://meded.dom.pitt.edu/. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.25 CE contact hours.

Lecture ID:

FP721201

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.