title: Negligible analgesic tolerance seen with extended release oxymorphone: a post hoc analysis of open-label longitudinal data.
abstract: OBJECTIVE
  To examine the development of analgesic tolerance in patients on oxymorphone extended-release (OxymER).
  
  
  METHODS
  Post hoc analysis of data from a previously conducted prospective 1 year multi-center open-label extension study in which patients were able to titrate as needed.
  
  
  METHODS
  Sample of 153 hip and knee osteoarthritis (OA) subjects on OxymER. Primary analyses were limited to study completers (n = 62) due to the large amount of missing data for the noncompleters (n = 91).
  
  
  METHODS
  Main outcome measures included OxymER doses (pill counts) and pain intensity ratings using a visual analog scale at monthly visits.
  
  
  RESULTS
  There were significant dose increases from weeks 1 to 2 and 2 to 6 (P < 0.05). Doses stabilized around week 6, suggesting the completion of what we defined as "titration." Both doses and pain ratings were stable when this titration phase was excluded from the analysis (P = 0.751; P = 0.056, respectively). Only 28% of the patients had any dose changes following this titration. While there was a significantly greater dose at week 52 compared with week 10 (P = 0.010), the increase in dose became insignificant after excluding four subjects who required two dose increases (P = 0.103).
  
  
  CONCLUSIONS
  The results showed that most of the titration/dose stabilization changes occurred within the first 10 weeks. A minority (28%) of subjects required dosage increases after this (defined) titration period. Pain reports stabilized statistically after 2 weeks. The findings of this post hoc analysis suggest a lack of opioid tolerance in the majority (72%) of these OA patients who completed this study following a defined titration period on OxymER.
  
  
  CONCLUSIONS
  This post hoc analysis of oxymorphone ER consumption in osteoarthritis pain vs pain report showed that most dose changes occurred during an initial "titration period" as defined. Following this titration few subjects increased dose and analgesia remained stable. These findings suggest a lack of longitudinal opioid tolerance in the majority of those OA subjects who completed the trial.
authors.affiliation: Center for Pain Studies, Rehabilitation Institute of Chicago, Chicago, Illinois 60611, USA. nharden@ric.org
authors.forename: R Norman
authors.initials: RN
authors.lastname: Harden
authors.forename: Christine M
authors.initials: CM
authors.lastname: Gagnon
authors.forename: Joseph
authors.initials: J
authors.lastname: Graciosa
authors.forename: Errol M
authors.initials: EM
authors.lastname: Gould
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D015207:Osteoarthritis, Hip / Q000188:drug therapy / Q000503:physiopathology; D020370:Osteoarthritis, Knee / Q000188:drug therapy / Q000503:physiopathology; D010111:Oxymorphone / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D010111:Oxymorphone