title: Sublingual buprenorphine/naloxone for chronic pain in at-risk patients: development and pilot test of a clinical protocol.
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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Treatment and Services Research, National Development and Research Institutes, New York, NY, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rosenblum
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Cruciani
authors.forename: Eric C
authors.initials: EC
authors.lastname: Strain
authors.forename: Charles M
authors.initials: CM
authors.lastname: Cleland
authors.forename: Herman
authors.initials: H
authors.lastname: Joseph
authors.forename: Stephen
authors.initials: S
authors.lastname: Magura
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Marsch
authors.forename: Laura F
authors.initials: LF
authors.lastname: McNicholas
authors.forename: Seddon R
authors.initials: SR
authors.lastname: Savage
authors.forename: Arun
authors.initials: A
authors.lastname: Sundaram
authors.forename: Russell K
authors.initials: RK
authors.lastname: Portenoy
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002047:Buprenorphine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069479:Buprenorphine, Naloxone Drug Combination; D059350:Chronic Pain / Q000188:drug therapy*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009270:Naloxone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D009293:Opioid-Related Disorders / Q000517:prevention & control; D010865:Pilot Projects; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D000069479:Buprenorphine, Naloxone Drug Combination; D009292:Narcotic Antagonists; D009270:Naloxone; D002047:Buprenorphine