Sublingual buprenorphine/naloxone for chronic pain in at-risk patients: Development and pilot test of a clinical protocol
DOI:
https://doi.org/10.5055/jom.2012.0137Keywords:
buprenorphine, chronic pain, treatment guidelines, opioid therapy, withdrawalAbstract
Objective: Sublingual buprenorphine/naloxone (Bup/Nx) is approved for addiction treatment and may be useful for pain management, particularly in opioid-treated patients with pain with nonadherence behaviors. The transition of opioid-treated patients with pain to buprenorphine carries the risk of precipitated withdrawal and increased pain. This study convened pain and addiction specialists to develop and pilot a clinical protocol for safe transitioning to Bup/Nx.
Design: The protocol was revised three times based on outside expert review and pilot study observations. The pilot was conducted with a prospective cohort of 12 patients with moderate to severe chronic pain, who were receiving long-term opioid therapy with any full µ-agonist drug, and had exhibited one or more aberrant drugrelated behaviors. Patients were followed up for 3-6 months with the expectation that they would experience few adverse events (AEs) and report lower pain severity.
Results: The three patients on the highest baseline opioid dose (equivalent to 303-450 mg of oral morphine) and the three on the lowest doses (≤20 mg) had early AEs when switched to Bup/Nx and did not complete the trial. Of the remaining six, one withdrew due to AEs; one responded well, then withdrew; and four completed a 3-month trial. A mixed-effects model controlling for dropouts found that average and worst pain significantly decreased after the switch to Bup/Nx (both p < 0.01).
Conclusion: Based on this experience, the protocol recommends Bup/Nx for pain only when baseline opioid doses are within bounds that reduce AEs at transition and incorporates dose flexibility to further reduce risks. This protocol warrants further testing.
References
World Health Organization (WHO): Cancer Pain Relief, with a Guide to Opioid Availability. 2nd ed. Geneva: WHO, 1996. Available at http://whqlibdoc.who.int/publications/ 9241544821.pdf. Accessed February 26, 2012.
Boudreau D, Von Korff M, Rutter CM, et al.: Trends in long-term opioid therapy for chronic non-cancer pain. Pharmacoepidemiol Drug Saf. 2009; 18: 1166-1175.
Johnson RE, Fudala PJ, Payne R: Buprenorphine: Considerations for pain management. J Pain Symptom Manage. 2005; 29: 297-326.
Compton WM, Volkow ND: Major increases in opioid analgesic abuse in the United States: Concerns and strategies. Drug Alcohol Depend. 2006; 81: 103-107.
Okie S: A flood of opioids, a rising tide of deaths. N Engl J Med. 2010; 363: 1981-1985.
Rosenblum A, Marsch LA, Joseph H, et al.: Opioids and the treatment of chronic pain: Controversies, current status, and future directions. Exp Clin Psychopharmacol. 2000; 16: 405-416.
Webster LR: Ending unnecessary opioid-related deaths: A national priority. Pain Med. 2011; 12: S13-S15.
Passik SD, Kirsh KL, Konaghy KB, et al.: Pain and aberrant drug-related behaviors in medically ill patients with and without histories of substance abuse. Clin J Pain. 2006; 22: 173-181.
Portenoy RK: Acute and chronic pain. In Ruiz P, Strain E (eds.): Lowinson & Ruiz’s Substance Abuse: A Comprehensive Textbook. 5th ed. Philadelphia: Lippincott, Williams & Wilkins, 2011: 695-720.
Savage SR, Kirsh KL, Passik SD: Challenges in using opioids to treat pain in persons with substance use disorders. Addict Sci Clin Pract. 2008; 42: 4-25.
Johnson RE, Strain EC, Amass L: Buprenorphine: How to use it right. Drug Alcohol Depend. 2003; 70: S59-S77.
Walsh SL, Preston KL, Bigelow GE, et al.: Acute administration of buprenorphine in humans: Partial agonist and blockade effects. J Pharmacol Exp Ther. 1995; 274: 361-372.
Dahan A, Yassen A, Romberg R, et al.: Buprenorphine induces ceiling in respiratory depression but not in analgesia. Br J Anaesth. 2006; 96: 627-632.
Umehara K, Shimokawa Y, Miyamoto G: Inhibition of human drug metabolizing cytochrome P450 by buprenorphine. Biol Pharm Bull. 2002; 25: 682-685.
Kress HG: Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine. Eur J Pain. 2009; 13: 219-230.
Pergolizzi J, Aloisi AM, Dahan A, et al.: Current knowledge of buprenorphine and its unique pharmacological profile. Pain Pract. 2010; 10: 428-450.
Davis MP: Twelve reasons for considering buprenorphine as a frontline analgesic in the management of pain. J Supportive Oncol. 2012; 10: 209-219.
Lutfy K, Cowan A: Buprenorphine: A unique drug with complex pharmacology. Curr Neuropharmacol. 2004; 2: 395-402.
Seldén T, Ahlner J, Druid H, et al.: Toxicological and pathological findings in a series of buprenorphine related deaths. Possible risk factors for fatal outcome. Forensic Sci Int. 2012; 220: 284-290.
Obadia Y, Perrin V, Feroni I, et al.: Injecting misuse of buprenorphine among French drug users. Addiction. 2001; 96: 267-272.
Pelissier-Alicot AL, Sastre C, Baillif-Couniou V, et al.: Buprenorphine-related deaths: Unusual forensic situations. Int J Legal Med. 2010; 124: 647-651.
Dasgupta N, Bailey EJ, Cicero T, et al.: Post-marketing surveillance of methadone and buprenorphine in the United States. Pain Med. 2010; 11: 1078-1091.
Lai SH, Teo CE: Buprenorphine-associated deaths in Singapore. Ann Acad Med Singapore. 2006; 35: 508-511.
Gatti A, Dauri M, Leonardis F, et al.: Transdermal buprenorphine in non-oncological moderate-to-severe chronic pain. Clin Drug Investig. 2010; 30(suppl 2): 31-38.
Griessinger N, Sittl R, Likar R: Transdermal buprenorphine in clinical practice–A post-marketing surveillance study in 13,179 patients. Curr Med Res Opin. 2005; 21: 1147-1156.
Gordon A, Rashiq S, Moulin DE, et al.: Buprenorphine transdermal system for opioid therapy in patients with chronic low back pain. Pain Res Manag. 2010; 15: 169-178.
Butrans Full Product Information. Stamford, CT: Purdue Pharma L.P. Available at http://www.purduepharma.com/pi/prescription/ButransPI.pdf. Accessed November 28, 2012.
SAMHSA: Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction, Treatment Improvement Protocol (TIP) Series 40. DHHS Publication No. (SMA) 04-3939. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2004. Available at http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=hssamhsatip&part=A72564. Accessed February, 26, 2012.
Daitch J, Frey ME, Silver D, et al.: Conversion of chronic pain patients from full-opioid agonists to sublingual buprenorphine. Pain Physician. 2012; 15: ES59-ES66.
Heit HA, Gourlay DL: Buprenorphine: New tricks with an old molecule for pain management. Clin J Pain. 2008; 24: 93-97.
Malinoff HL, Barkin RL, Wilson G: Sublingual buprenorphine is effective in the treatment of chronic pain syndrome. Am J Ther. 2005; 12: 379-384.
Blondell RD, Ashrafioun L, Dambra CM, et al.: A clinical trial comparing tapering doses of buprenorphine with steady doses for chronic pain and co-existent opioid addiction. J Addict Med. 2010; 4: 140-146.
Rosado J, Walsh SL, Bigelow GE, et al.: Sublingual buprenorphine/naloxone precipitated withdrawal in subjects maintained on 100 mg of daily methadone. Drug Alcohol Depend. 2007; 90: 261-269.
Comer SD, Sullivan MA, Vosburg SK, et al.: Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusers. Addiction. 2010; 105: 709-718.
Butler SF, Budman SH, Fernandez KC, et al.: Development and validation of the Current Opioid Misuse Measure. Pain. 2007; 130: 144-156.
Sheehan DV, Lecrubier Y, Sheehan KH, et al.: The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998; 59(suppl 20): 22-33; quiz 34-57.
Stanton A, McLeod CC, Kissin W, et al.: Results from SAMHSA/CSAT’s national evaluation of the buprenorphine waiver program. Presented at CPDD, Orlando, FL, 2005. Available at http://buprenorphine.samhsa.gov/ASAM_06_Final_Results.pdf. Accessed February 26, 2012.
Rosen CS, Drescher KD, Moos RH, et al.: Six- and ten-item indexes of psychological distress based on the Symptom Checklist-90. Assessment. 2000; 7: 103-111.
Derogatis LR, Lipman RS, Covi L: The SCL-90: An outpatient psychiatric rating scale–Preliminary report. Psychopharmacol Bull. 1973; 9: 13-28.
Flynn PM, Hubbard RL, Luckey JW, et al.: Individual Assessment Profile (IAP): Standardizing the assessment of substance abusers. J Subst Abuse Treat. 1995; 12: 213-221.
Cleeland CS, Ryan KM: Pain assessment: Global use of the Brief Pain Inventory. Ann Acad Med Singapore. 1994; 23: 129-138.
Wesson DR, Ling W: The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs. 2003; 35: 253-259.
Handelsman L, Cochrane KJ, Aronson MJ, et al.: Two new rating scales for opiate withdrawal. Am J Drug Alcohol Abuse. 1987; 13: 293-308.
Pinheiro J, Bates D, DebRoy S, et al.: nlme: Linear and Nonlinear Mixed Effects Models. R package version 3.1-102, 2011.
R Development Core Team: R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing, 2011. ISBN 3-900051-07-0. Available at http://www.R-project.org/. Accessed February 27, 2012.
Weiss RD, Potter JS, Fiellin DA, et al.: Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: A 2-phase randomized controlled trial. Arch Gen Psychiatry. 2011; 68: 1238-1246.
Fine PG, Portenoy RK: A Clinical Guide to Opioid Analgesia. New York, NY: Vendome Group, LLC, 2007.
Fine PG, Portenoy RK: Establishing “best practices” for opioid rotation: Conclusions of an expert panel. J Pain Symptom Manage. 2009; 38: 418-425.
Levy MH: Pharmacologic treatment of cancer pain. New Engl J Med. 1996; 335: 1124-1132.
Duragesic insert. Raritan, NJ: Ortho-McNeil-Janssen Pharmaceuticals, Inc., 2009.
Published
How to Cite
Issue
Section
License
Copyright 2005-2024, Weston Medical Publishing, LLC
All Rights Reserved
