Sublingual buprenorphine/naloxone for chronic pain in at-risk patients: development and pilot test of a clinical protocol

• Published in: Journal of opioid management Vol. 8; no. 6; p. 369
• Main Authors: Rosenblum, Andrew, Cruciani, Ricardo A, Strain, Eric C, Cleland, Charles M, Joseph, Herman, Magura, Stephen, Marsch, Lisa A, McNicholas, Laura F, Savage, Seddon R, Sundaram, Arun, Portenoy, Russell K
• Format: Journal Article
• Language: English
• Published: United States 01.11.2012
• Subjects: Administration, Sublingual; Adult; Aged; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - adverse effects; Analgesics, Opioid - therapeutic use; Buprenorphine - administration & dosage; Buprenorphine - adverse effects; Buprenorphine - therapeutic use; Buprenorphine, Naloxone Drug Combination; Chronic Pain - drug therapy; Cohort Studies; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Middle Aged; Models, Statistical; Naloxone - administration & dosage; Naloxone - adverse effects; Naloxone - therapeutic use; Narcotic Antagonists - administration & dosage; Narcotic Antagonists - adverse effects; Narcotic Antagonists - therapeutic use; Opioid-Related Disorders - prevention & control; Pilot Projects; Prospective Studies; Severity of Illness Index; Treatment Outcome
• ISSN: 1551-7489
• DOI: 10.5055/14

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. 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 m-agonist drug, and had exhibited one or more aberrant drug-related 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. 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). 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.