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.2012.0137aAbstract
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.
Keywords: buprenorphine, chronic pain, treatment guidelines, opioid therapy, withdrawal
DOI:10.5055/jom.2012.0137
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 longterm 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.
; 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,
: 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:
-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;
: 284-290.
Obadia Y, Perrin V, Feroni I, et al.: Injecting misuse of
buprenorphine among French drug users. Addiction. 2001; 96:
-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
,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
Journal of Opioid Management 8:6 November/December 2012 381
Charles M. Cleland, PhD, Institute for Treatment and
Services Research, National Development and Research
Institutes, New York, New York; College of Nursing, New York
University, New York, New York.
Herman Joseph, PhD, Institute for Treatment and Services
Research, National Development and Research Institutes,
New York, New York.
Stephen Magura, PhD, CSW, The Evaluation Center, Western
Michigan University, Kalamazoo, Michigan.
Lisa A. Marsch, PhD, Center for Technology and Behavioral
Health, Dartmouth Psychiatric Research Center, Department
of Psychiatry, Dartmouth College, Lebanon, New Hampshire.
Laura F. McNicholas, MD, PhD, Department of Psychiatry,
University of Pennsylvania, Philadelphia, Pennsylvania.
Seddon R. Savage, MD, MS, Center on Addiction Recovery
and Education, Dartmouth Medical School, Hanover, New
Hampshire.
Arun Sundaram, BA, Department of Pain Medicine and
Palliative Care, Beth Israel Medical Center, New York, New
York.
Russell K. Portenoy, MD, Department of Pain Medicine and
Palliative Care, Beth Israel Medical Center, New York, New
York; Department of Neurology, Albert Einstein College of
Medicine, Bronx, New York; Department of Anesthesiology,
Albert Einstein College of Medicine, Bronx, New York.
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.
; 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.
; 130: 144-156.
Sheehan DV, Lecrubier Y, Sheehan KH, et al.: The MiniInternational 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;
(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.
; 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,
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.
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