Buprenorphine for Chronic Pain: A Safer Alternative to Traditional Opioids

With the ongoing public health crisis with prescription opioids, there is a need for safer alternatives for medication management in chronic pain patients. Buprenorphine is a partial mu-opioid agonist which is commonly utilized to treat patients with opioid-use disorders. The purpose of this review is to discuss the potential use of this medication for the treatment of chronic pain instead of resorting to more traditional Schedule II opioids. Buprenorphine offers a safer alternative for patients who require opioids to manage chronic pain, given the unique pharmacological properties that allow it to provide adequate analgesia with less abuse potential.
1. Dahlhamer J, Lucas J, Zelaya, C, et al. Prevalence of chronic pain and high-impact chronic pain among adults—United States, 2016. Morb Mortal Wkly Rep. 2018;67(36):1001-1006. doi:10.15585/mmwr.mm6736a2
2. Substance Abuse and Mental Health Services Administration. Key Substance Use and Mental Health Indicators in the United States: Results from the 2017 National Survey on Drug Use and Health (HHS Publication No. SMA 18-5068, NSDUH Series H-53).; 2018. https://www.samhsa.gov/data/report/2017-nsduh-annual-national-report
3. Rosenblum A, Marsch LA, Joseph H, Portenoy RK. Opioids and the treatment of chronic pain: Controversies, current status, and future directions. Exp Clin Psychopharmacol. 2008;16(5):405-416. doi:10.1037/a0013628
4. Sun EC, Dixit A, Humphreys K, Darnall BD, Baker LC, Mackey S. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ. 2017;356. doi:10.1136/bmj.j760
5. Gudin J, Fudin J. A Narrative Pharmacological Review of Buprenorphine: A Unique Opioid for the Treatment of Chronic Pain. Pain Ther. 2020;9(1):41-54. doi:10.1007/s40122-019-00143-6
6. Pasternak G, Pan YX. Mu opioid receptors in pain management. Acta Anaesthesiol Taiwan. 2011;49(1):21-25. doi:10.1016/j.aat.2010.12.008
7. Chin Beng Lim S, Schug S, Krishnarajah J. The Pharmacokinetics and Local Tolerability of a Novel Sublingual Formulation of Buprenorphine. Pain Med. 2019;20(1):143-152. doi:10.1093/pm/pnx321
8. Bai SA, Xiang Q, Finn A. Evaluation of the Pharmacokinetics of Single- and Multiple-dose Buprenorphine Buccal Film in Healthy Volunteers. Clin Ther. 2016;38(2):358-369. doi:10.1016/j.clinthera.2015.12.016
9. Ciraulo DA, Hitzemann RJ, Somoza E, et al. Pharmacokinetics and pharmacodynamics of multiple sublingual buprenorphine tablets in dose-escalation trials. J Clin Pharmacol. 2006;46(2):179-192. doi:10.1177/0091270005284192
10. Donaher PA, Welsh C. Managing opioid addiction with buprenorphine. Am Fam Physician. 2006;73(9):1573-1578.
11. Ahmadi J, Sahraian A, Biuseh M. A randomized clinical trial on the effects of bupropion and buprenorphine on the reduction of methamphetamine craving. Trials. 2019;20(1):1. doi:10.1186/s13063-019-3554-6
12. Webster L, Gruener D, Kirby T, Xiang Q, Tzanis E, Finn A. Evaluation of the tolerability of switching patients on chronic full μ-opioid agonist therapy to buccal buprenorphine. Pain Med (United States). 2016;17(5):899-907.
13. Fishman MA, Kim PS. Buprenorphine for Chronic Pain: a Systemic Review. Curr Pain Headache Rep. 2018;22(12):83. doi:10.1007/s11916-018-0732-2
14. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021306s015s019lbl.pdf
15. Busse JW, Wang L, Kamaleldin M, et al. Opioids for Chronic Noncancer Pain: A Systematic Review and Meta-analysis. JAMA. 2018;320(23):2448-2460. doi:10.1001/jama.2018.18472
16. Daitch J, Frey ME, Silver D, et al. Conversion of chronic pain patients from full-opioid agonists to sublingual buprenorphine. Pain Phys. 2012;15(suppl 3):ES59-ES66. doi:10.36076/ppj.2012/15/es59
17. Cote J, Montgomery L. Sublingual buprenorphine as an analgesic in chronic pain: a systematic review. Pain Med. 2014;15(7):1171-1178. doi:10.1111/pme.12386
18. James IGV, O’Brien CM, McDonald CJ. A randomized, doubleblind, double-dummy comparison of the efcacy and tolerability of low-dose transdermal buprenorphine (BuTrans seven-day patches) with buprenorphine sublingual tablets (Temgesic) in patients with osteoarthritis pain. J Pain Symp Manag. 2010;40(2):266-278. doi:10.1016/j.jpainsymman.2010.01.013
19. Naing C, Yeoh PN, Aung K. A meta-analysis of efficacy and tolerability of buprenorphine for the relief of cancer pain. SpringerPlus. 2014;3(1):87. doi:10.1186/2193-1801-3-87
20. Within PJ, Derry S, Moore RA, Stannard C, Aldington D, Cole P, et al. Buprenorphine for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;(9):CD011603.
21. Buprenorphine for Chronic Pain: A Review of the Clinical Effectiveness. Canadian Agency for Drugs and Technologies in Health; 2017.
22. Ventafridda V, Saita L, Ripamonti C, De Conno F. WHO guidelines for the use of analgesics in cancer pain. Int J Tissue React. 1985;7:93-96.
23. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. MMWR Recomm Rep. 2016;65(1):1-49. doi:10.15585/mmwr.rr6501e1
24. Dahan A. Opioid-induced respiratory effects: new data on buprenorphine. Palliat Med. 2006;20(Suppl 1):s3-s8.
25. Walsh SL, Eissenberg T. The clinical pharmacology of buprenorphine: extrapolating from the laboratory to the clinic. Drug Alcohol Depend. 2003;70(Suppl 2):S13-S27. doi:10.1016/s0376-8716(03)00056-5
26. Lim SCB, Schug S, Krishnarajah J. The Pharmacokinetics and Local Tolerability of a Novel Sublingual Formulation of Buprenorphine. Pain Med. 2019;20(1):143-152. doi:10.1093/pm/pnx321
27. Davis MP. Twelve reasons for considering buprenorphine as a frontline analgesic in the management of pain. J Support Oncol. 2012;10(6):209-219. doi:10.1016/j.suponc.2012.05.002
28. Sullivan JG, Webster L. Novel buccal film formulation of buprenorphine-naloxone for the maintenance treatment of opioid dependence: a 12-week conversion study. Clin Ther. 2015;37(5):1064-1075. doi:10.1016/j.clinthera.2015.02.027
29. Kraan H, Vrieling H, Czerkinsky C, Jiskoot W, Kersten G, Amorij JP. Buccal and sublingual vaccine delivery. J Control Release. 2014;190:580-592. doi:10.1016/j.jconrel.2014.05.060
30. Mendelson J, Upton RA, Everhart ET, Jacob P III, Jones RT. Bioavailability of sublingual buprenorphine. J Clin Pharmacol. 1997;37(1):31-37. doi:10.1177/009127009703700106
31. Davis MP, Pasternak G, Behm B. Treating Chronic Pain: An Overview of Clinical Studies Centered on the Buprenorphine Option. Drugs. 2018;78(12):1211-1228. doi:10.1007/s40265-018-0953-z
32. Rauck RL, Potts J, Xiang Q, Tzanis E, Finn A. Efficacy and tolerability of buccal buprenorphine in opioid-naive patients with moderate to severe chronic low back pain. Postgrad Med. 2016;128(1):1-11. doi:10.1080/00325481.2016.1128307
33. Pergolizzi JV Jr, Taylor R Jr, LeQuang JA, Lara A, Ortiz AH, Iban MAR. Pain Control in Latin America: The Optimized Role of Buprenorphine in the Treatment of Cancer and Noncancer Pain. Pain Ther. 2019;8(2):187-201. doi:10.1007/s40122-019-0126-0
34. Plosker GL. Buprenorphine 5, 10 and 20 LG/h Transdermal Patch: A Review of Its Use in the Management of Chronic Non-Malignant Pain.
35. Yarlas A, Miller K, Wen W, et al. Buprenorphine transdermal system improves sleep quality and reduces sleep disturbance in patients with moderate-to-severe chronic low Back pain: results from two randomized controlled trials. Pain Pract. 2015;16(3):345-358. doi:10.1111/papr.12281
36. James IGV, O’Brien CM, McDonald CJ. A randomized, doubleblind, double-dummy comparison of the efcacy and tolerability of low-dose transdermal buprenorphine (BuTrans seven-day patches) with buprenorphine sublingual tablets (Temgesic) in patients with osteoarthritis pain. J Pain Symp Manag. 2010;40(2):266-278. doi:10.1016/j.jpainsymman.2010.01.013
37. Naing C, Yeoh PN, Aung K. A meta-analysis of efficacy and tolerability of buprenorphine for the relief of cancer pain. SpringerPlus. 2014;3(1):87. doi:10.1186/2193-1801-3-87
38. Conaghan PG, O’Brien CM, Wilson M, Schofield JP. Transdermal buprenorphine plus oral paracetamol vs an oral codeine-paracetamol combination for osteoarthritis of hip and/or knee: A randomised trial. Osteoarthritis and Cartilage. 2011;19(8):930-938. doi:10.1016/j.joca.2011.03.011
39. Wallace L, Kadakia A. Buprenorphine transdermal system utilization. Postgrad Med. 2017;129(1):81-86. doi:10.1080/00325481.2017.1267537
40. Raffa RB, Haidery M, Huang HM, et al. The clinical analgesic efficacy of buprenorphine. J Clin Pharm Ther. 2014;39(6):577-583. doi:10.1111/jcpt.12196
41. Pergolizzi J, Aloisi AM, Dahan A, et al. Current Knowledge of Buprenorphine and Its Unique Pharmacological Profile. Pain Practice. 2010;10(5):428-450. doi:10.1111/j.1533-2500.2010.00378.x
42. Pergolizzi J, Böger RH, Budd K, et al. Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone). Pain Pract. 2008;8(4):287-313. doi:10.1111/j.1533-2500.2008.00204.x
43. Al-Tawil N, Odar-Cederlöf I, Berggren AC, Johnson HE, Persson J. Pharmacokinetics of transdermal buprenorphine patch in the elderly. Eur J Clin Pharmacol. 2013;69(2):143-149. doi:10.1007/s00228-012-1320-8
44. Filitz J, Griessinger N, Sittl R, Likar R, Schüttler J, Koppert W. Effects of intermittent hemodialysis on buprenorphine and norbuprenorphine plasma concentrations in chronic pain patients treated with transdermal buprenorphine. Eur J Pain. 2006;10(8):743-748. doi:10.1016/j.ejpain.2005.12.001
45. Nasser AF, Heidbreder C, Liu Y, Fudala PJ. Pharmacokinetics of sublingual buprenorphine and naloxone in subjects with mild to severe hepatic impairment (child-pugh classes A, B, and C), in hepatitis C virus-seropositive subjects, and in healthy volunteers. Clin Pharmacokinet. 2015;54(8):837-849. doi:10.1007/s40262-015-0238-6
46. Butrans (buprenorphine) Transdermal System for transdermal administration: US prescribing information. http://www.purduepharma.com/pi/prescription/butranspi.pdf
47. BuTrans 5, 10 and 20 ug/h transdermal patch: EU summary of product characteristics. http://www.medicines.org.uk/emc/medicine/16787
48. Baker JR, Best AM, Pade PA, McCance-Katz EF. Effect of buprenorphine and antiretroviral agents on the QT interval in opioid-dependent patients. Ann Pharmacother. 2006;40(3):392-396. doi:10.1345/aph.1g524
49. Kao DP, Haigney MCP, Mehler PS, Krantz MJ. Arrhythmia associated with buprenorphine and methadone was reported to the Food and Drug Administration. Addiction. 2015;110(9):1468-1475. doi:10.1111/add.13013
50. Simpson RW, Wlodarczyk JH. Transdermal buprenorphine relieves neuropathic pain: a randomized, double-blind, parallel-group, placebo-controlled trial in diabetic peripheral neuropathic pain. Dia Care. 2016;39(9):1493-1500. doi:10.2337/dc16-0123
51. Yoon DH, Bin SI, Chan SKC, et al. effectiveness and tolerability of transdermal buprenorphine patches: a multicenter, prospective, open-label study in Asian patients with moderate to severe chronic musculoskeletal pain. BMC Musculoskelet Disord. 2017;18(1):337. doi:10.1186/s12891-017-1664-4