Reduced cognitive and psychomotor impairment with extended-release oxymorphone versus controlled-release oxycodone.

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) Study design Randomized double blind 5 way crossover Setting 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<0 001 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) Limitations 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