title: Reduced cognitive and psychomotor impairment with extended-release oxymorphone versus controlled-release oxycodone.
abstract: BACKGROUND
  Opioids provide effective pain control, yet have risks including adverse events (AEs) (e.g., constipation, nausea/vomiting, sedation) and cognitive/psychomotor effects.
  
  
  OBJECTIVE
  To compare cognitive and psychomotor effects of oxymorphone extended release (OM-ER) versus oxycodone controlled release (OC-CR).
  
  
  METHODS
  Randomized, double-blind, 5-way crossover
  
  
  METHODS
  Single inpatient research unit
  
  
  METHODS
  Nondependent recreational opioid users were administered single intact oral tablets of placebo, OM-ER (15 and 30 mg), and OC-CR (30 and 60 mg), separated by a 7- to 21-day washout. The divided attention (DA) test measured psychomotor impairment (e.g., manual tracking [e.g., percentage over road], target accuracy [e.g., target hits], reaction time [hit latency]). Visual analog scales measured alertness/drowsiness, agitation/relaxation, and dizziness. Sedative, stimulant, and dysphoric effects were measured using the Addiction Research Center Inventory Pentobarbital-Chlorpromazine-Alcohol (PCAG), Benzedrine Group (BG), and Lysergic Acid Diethylamide (LSD) scales, respectively. Comparisons were made between equianalgesic doses (OM-ER 15 mg vs OC-CR 30 mg; OM-ER 30 mg vs OC-CR 60 mg), within active drug doses, and between active drugs and placebo using least squares (LS) mean difference of the peak maximum (Emax) or minimum (Emin) effect using linear mixed model analysis of covariance.
  
  
  RESULTS
  Thirty-five participants received all 5 treatments. Peak cognitive and psychomotor impairment (LS mean [SE]) was less with OM-ER than equianalgesic doses of OC-CR for reaction time (Emax hit latency, longer if impaired; 571.2 [13.4] vs 588.1 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], P<0.001 for OM-ER 30 mg vs OC-CR 60 mg, respectively); tracking accuracy (Emin percentage over road, lower if impaired; 71.4 [2.4] vs 65.3 [2.4], P=0.007; 69.9 [2.4] vs 59.4 [2.4], P<0.001), and target accuracy (Emin target hits percentage, lower if impaired; 81.0 [3.1] vs 74.5 [3.1], P=0.02; 79.4 [3.1] vs 66.1 [3.1], P<0.001). Several other DA measures showed that OC-CR, especially 60 mg, produced more psychomotor impairment than equianalgesic OM-ER. Compared to OM-ER, OC-CR produced more dizziness (Emax, P<0.001 for OM-ER 15 mg vs OC-CR 30 mg and for OM-ER 30 mg vs OC-CR 60 mg), drowsiness (Emax, P<0.001 for both equianalgesic dose groups), relaxation (Emin, P=0.003 for OM-ER 15 mg vs OC-CR 30 mg; P=0.001 for OM-ER 30 mg vs OC-CR 60 mg), dysphoria (Emax LSD, P<0.001 for both equianalgesic dose groups), and sedation (Emax, PCAG; P<0.001 for both equianalgesic dose groups) and less stimulation (BG, Emin; P=0.01 for OM-ER 15 mg vs OC-CR mg; P<0.001 for OM-ER 30 mg vs OC-CR 60 mg). Several AEs occurred more commonly with OC-CR than OM-ER (e.g., euphoria, nausea, somnolence, vomiting, dizziness).
  
  
  CONCLUSIONS
  Participants were young, healthy volunteer nondependent recreational drug users, and only single doses were evaluated. The effects of tampering or higher doses were not assessed.
  
  
  CONCLUSIONS
  Single oral intact low and high doses of OM-ER produced less cognitive and psychomotor impairment plus less sedation than equianalgesic OC-CR in this exploratory study. ClinicalTrials.gov registration NCT00955110.
authors.affiliation: Kendle Early Stage, Toronto, ON, Canada. schoedel.kerri@kendle.com
authors.forename: Kerri A
authors.initials: KA
authors.lastname: Schoedel
authors.forename: Stephen
authors.initials: S
authors.lastname: McMorn
authors.forename: Bijan
authors.initials: B
authors.lastname: Chakraborty
authors.forename: Kathleen
authors.initials: K
authors.lastname: Zerbe
authors.forename: Edward M
authors.initials: EM
authors.lastname: Sellers
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000175:diagnosis / Q000517:prevention & control; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010098:Oxycodone / Q000008:administration & dosage* / Q000009:adverse effects; D010111:Oxymorphone / Q000008:administration & dosage* / Q000009:adverse effects; D010148:Intractable Pain / Q000188:drug therapy*; D011596:Psychomotor Disorders / Q000139:chemically induced* / Q000175:diagnosis / Q000517:prevention & control; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D010111:Oxymorphone; D010098:Oxycodone