Reduced cognitive and psychomotor impairment with extended-release oxymorphone
versus controlled-release oxycodone.
Author(s): Schoedel KA, McMorn S, Chakraborty B, Zerbe K, Sellers EM.
Affiliation(s): Kendle Early Stage, Toronto, ON, Canada. schoedel.kerri@kendle.com
Publication date & source: 2010, Pain Physician. , 13(6):561-73
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=0.03 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.
CONCLUSION: 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.
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