Rationale. Medications combining hydrocodone bitartrate and non-steroidal anti-inflammatory agents appear more beneficial than anti-inflammatory medications alone in treating pain and inflammation from acute soft tissue trauma, but opiate side effects may include sedation and impaired cognitive and motor performance.

Objective. Performance on complex cognitive and motor tasks was evaluated in healthy subjects with exercise-induced muscle damage who were treated with a hydrocodone-ibuprofen combination, ibuprofen alone, or placebo.

Methods. This double-blind, randomized, placebo-controlled, repeated-dose clinical trial compared the effects of hydrocodone bitartrate (7.5 mg) plus ibuprofen (200 mg), ibuprofen alone, and placebo on cognitive and motor function in 72 healthy college men. Muscle damage in the quadriceps of each subject's dominant leg was induced by an eccentric exercise protocol. Subjects took the study medication four times daily (every 4–6 h) for 5 days. Forty minutes after medication ingestion at the same time each day, subjects underwent tests of attention/concentration, motor performance, and reaction time. Four trained assessors rotated among subjects so that none tested the same participant on more than three occasions.

Results. Repeated measures analyses of covariance revealed no between-group differences on a complex memory and cognition task or complex reaction time. Subjects using hydrocodone bitartrate plus ibuprofen performed significantly less well on a simple tracking task and made significantly more errors on a simple reaction-time task than the other two groups. These deficits were found to be highly transitory and not related to confusion or fatigue.

Conclusion. Hydrocodone plus ibuprofen was not associated with deterioration in complex cognition but was related to very transitory decrements in tasks involving simple hand-eye coordination.