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Using Buprenorphine to Reduce Opioid Need in Chronic Pain Patients

NANCY IBRAHIM

Lewis Katz School of Medicine



SUMMARY POINTS

  • Opioids are a poor treatment tool for chronic pain given their adverse risk profile.

  • Emerging research points to buprenorphine being a safer tool to decrease opioid dependence than methadone.

  • More research needs to be done to avoid opioid withdrawal when prescribing buprenorphine.

  • Buprenorphine can successfully decrease opioid dosages for patients with chronic pain.

 


ANALYSIS

Background


Chronic pain is a crisis globally but particularly in the U.S. (2). Despite it being well studied that opioids carry many side effects with long term use such as constipation, xerostomia, and high risk for abuse, 5-8% of Americans suffering chronic pain are prescribed opioids long-term (1). While patients suffering acute injuries or recovering from surgery do benefit from being prescribed a small supply of opioids, the harm comes from poorly managed prescriptions. There exists a knowledge gap amongst providers on matters such as the difference between addiction and dependence, and what quantity of opioids is necessary to prescribe for acute matters (2). This can oftentimes precipitate a cycle of dependency, in which patients go from using opioids for an acute matter to requiring them chronically.


Chronic opioid use also carries the risk of opioid-induced hyperalgesia (OIH), the paradoxical phenomenon in which the very medication designed to reduce a patient’s pain actually lowers their pain threshold (5). This causes patients to continually need higher opioid doses to handle their pain, but this unfortunately also exacerbates the problem. The only way to definitively avoid this is to prevent chronic opioid use in the first place. However there does exist an opioid on the market that serves to help wean patients off chronic opioids: buprenorphine. Unlike most opioids prescribed for pain management which are full mu receptor agonists, buprenorphine is a partial mu agonist. This drug conveys several benefits including lowered risk of respiratory depression, and its physiological effects reach a plateau, thereby reducing the potential for abuse. (6).  While full agonist opioids fall in the Schedule II category, buprenorphine is in the safer category of Schedule III (7).  Such an example of a Schedule II opioid is methadone, approved by the FDA for treatment of opioid use disorder in 1972, 30 years before the FDA approved the newer buprenorphine in 2002 (11). Providers note its more adverse risk profile with up to 1/3 of patients taking methadone experiencing arrhythmias and QT interval prolongation (9). Buprenorphine very rarely carries this risk and is often formulated as a combination drug with naloxone, bup/nal, to prevent intravenous misuse and further improve its safety profile (9). With less abuse potential and a tool to relieve hyperalgesia, buprenorphine is a powerful medication for patients who need to reduce or stop their chronic opioid use.





FIGURE 1: Comparison of Buprenorphine vs. Methadone's agonist effects.

[Reprinted with permission from Journal of Pain and Symptom Management (9)]



 

Analysis



There exists a misunderstanding that buprenorphine being a partial agonist does not provide adequately potent analgesia for chronic pain. Buprenorphine is available via sublingual and transdermal formulations, which aside from increasing accessibility as outpatient options, also pharmacokinetically confer longer half-lives (4).    



FIGURE 2: Timeline of Buprenorphine’s Availability for Chronic Pain.                             [Reprinted with permission from Pain Medicine (4)]




Prescribing a buprenorphine course can be done via rapid or standard induction (12). Consider the case of a 66-year-old female in 2018 who successfully underwent rapid induction (8). At age 64, she suffered an L2 compression fracture which progressed to full lumbar disc degeneration, resulting in extensive T11-L5 fusion surgery. Post-operatively, she was prescribed oxycodone which escalated to a high need of 200mg daily. After suffering severe constipation and poor pain relief, her providers prescribed methadone adjunctively. This provided minimal relief, and at this point she began a 5-day rapid induction course. She transitioned off methadone and oxycodone to bup/nal incrementally, and after the 5th day reported independent ambulation and significant pain relief.   



                                       

FIGURE 3: Rapid induction titration schedule for bup/nal from methadone plus oxycodone.

[Reprinted from A&A Practice (8)]

 

Existing literature on success stories of weaning chronic pain patients off full agonist opioids using buprenorphine is scarce. In a conversation with Dr. Shahnaz Bari, MD, (June 2023) an anesthesiologist, she detailed a standard induction case of one of her patients. A 44-year-old male came to her due to reports of poor pain relief from his opioid regimen. Five years prior he was in an MVC which resulted in two cervical herniated discs and lumbar radiculopathy. The patient required a cervical fusion, following which he tried physical therapy and several nerve blocks that did not provide relief. Upon seeing Dr. Bari, the patient was taking 15mg oxycodone every 6 hours and dilaudid ER. Dr. Bari initiated a standard induction of sublingual buprenorphine 75mcg twice daily, with hydrocodone restricted for breakthrough pain. While previously the patient had greatly diminished quality of life, 6 weeks later he was entirely off oxycodone, rarely requiring hydrocodone, and finding great relief in his activities of daily living. Dr. Bari noted that in her experience, for patients who are long-term opioid users, the sublingual formulation is often preferred over the transdermal patch, due to the psychological component of being more similar to taking oral pills they are used to. Cases like this highlight the efficacy of buprenorphine for chronic pain patients.

For the first 20 years of its use in the U.S., buprenorphine could not be prescribed without physicians obtaining a waiver from the DEA called the X-Waiver. Subsequently, physicians have been under-prescribing buprenorphine with the top cited reasons including confusion on how to obtain the waiver and lack of capacity to accept new patients (10).   However, in December 2022 the Biden Administration signed into law an act removing the waiver requirement, and eliminating the prior cap on number of patients providers could prescribe buprenorphine to. As of November 2023, providers will be able to prescribe buprenorphine via telehealth to new patients, easing socioeconomic barriers to access (3).

 


Discussion



More research on chronic pain patients reporting success with buprenorphine need to be published to increase its prescription rates. Future research should focus on what dosage of buprenorphine is ideal for varying pain levels with as much patient data collection as possible. Research on safest starter doses and most effective follow up time periods will minimize precipitated withdrawal. Legislature easing restrictions on providers, coupled with increasing provider education, will enable the popularization of buprenorphine to ultimately decrease opioid dependence. Given the many side effects of long-term opioid use, it is increasingly vital to utilize safer alternatives for chronic pain management.

 


REFERENCES



1. Thomas DA, Denisco RA. NATIONAL INSTITUTES of HEALTH Pathways to Prevention Workshop: The Role of Opioids in the Treatment of Chronic Pain EXECUTIVE SUMMARY.;2014.https://prevention.nih.gov/sites/default/files/documents/programs/p2p/ODPPainPanelStatementFinal_10-02-14.pdf

2. Horn DB, Vu L, Porter BR, Sarantopoulos K. Responsible Controlled Substance and Opioid Prescribing. PubMed. Published 2022. https://www.ncbi.nlm.nih.gov/books/NBK572085/

3. Volpe KD. What the Buprenorphine X-Waiver Removal Means for Clinicians. Clinical Advisor. Published January 26, 2023. Accessed August 28, 2023. https://www.clinicaladvisor.com/home/topics/psychiatry-information-center/buprenorphine-x-waiver-opioid-use-disorder/#:~:text=Prescribing%20buprenorphine%20for%20opioid%20use

4. Webster L, Gudin J, Raffa RB, et al. Understanding Buprenorphine for Use in Chronic Pain: Expert Opinion. Pain Medicine. 2020;21(4):714-723. doi:https://doi.org/10.1093/pm/pnz356

5. Angst MS, Clark JD. Opioid-induced Hyperalgesia. Anesthesiology. 2006;104(3):570-587. doi:https://doi.org/10.1097/00000542-200603000-00025

6. Johnson RE, Fudala PJ, Payne R. Buprenorphine: Considerations for Pain Management. Journal of Pain and Symptom Management. 2005;29(3):297-326. doi:https://doi.org/10.1016/j.jpainsymman.2004.07.005

7. Dalal S, Chitneni A, Berger AA, et al. Buprenorphine for Chronic Pain: A Safer Alternative to Traditional Opioids. Health Psychology Research. 2021;9(1). doi:https://doi.org/10.52965/001c.27241

8. Lee DS, Hann JE, Klaire SS, Nikoo M, Negraeff MD, Rezazadeh-Azar P. Rapid Induction of Buprenorphine/Naloxone for Chronic Pain Using a Microdosing Regimen: A Case Report. A&A Practice. 2020;14(2):44-47. doi:https://doi.org/10.1213/XAA.0000000000001138

9. Huhn AS, Dunn KE. Why aren’t physicians prescribing more buprenorphine? Journal of Substance Abuse Treatment. 2017;78:1-7. doi:https://doi.org/10.1016/j.jsat.2017.04.005

11. Treatment I of M (US) C on FR of M, Rettig RA, Yarmolinsky A. Executive Summary. National Academies Press (US); 1995. https://www.ncbi.nlm.nih.gov/books/NBK232111/#:~:text=Approved%20by%20the%20Food%20and

12. Wong JSH, Nikoo M, Westenberg JN, et al. Comparing rapid micro-induction and standard induction of buprenorphine/naloxone for treatment of opioid use disorder: protocol for an open-label, parallel-group, superiority, randomized controlled trial. Addiction Science & Clinical Practice. 2021;16(1). doi:https://doi.org/10.1186/s13722-021-00220-2

 

 

 

 

 

 

 

 

 

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