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

舌下含服丁丙诺啡/纳洛酮治疗高危慢性疼痛患者:临床方案的制定和试点测试

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Abstract

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 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. 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.

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