Effect of carbamazepine on psychomotor performance in näive subjects

Summary

The effect of a single dose of carbamazepine (CBZ), 10 mg kg⁻¹, on a battery of simple psychomotor tests was investigated in 12 healthy subjects (6 male, 6 female) in a balanced randomised double blind placebo controlled cross-over study. Psychomotor testing and blood sampling for total and free plasma CBZ, and CBZ 10, 11 epoxide concentration were performed at 10, 12, 14, 16, 18 and 34 h after oral dosing (23.00 h the previous evening). CBZ impaired i) critical flicker fusion threshold frequency at all time points up to 18 h (p<0.005); ii) total choice reaction time at 10 h (p<0.005) and 18 h (p<0.008); iii) card sorting at 14 h (p<0.001).

No significant effect on finger tapping was noted. Subjects adjudged themselves more sedated on CBZ as compared to placebo at 12, 14 and 16 h (p<0.008). Plasma total and free CBZ concentrations (mean ± SD) peaked at 10 h (8.8±0.2 mg l⁻¹) and 16 h (1.88±0.3 mg l⁻¹) after dosing respectively. CBZ 10, 11 epoxide values were all less than 10% of total CBZ concentrations and, therefore, were unlikely to contribute to the pharmacodynamic effect. Total choice reaction time was significantly more impaired in females (p<0.05) but no sex difference occurred with the other tests or CBZ concentrations at any time point. No significant correlations were found between individual total or free CBZ concentrations and corresponding test performances at each time point. This study has demonstrated impairment of psychomotor function following CBZ in healthy subjects using a series of simply performed tests. This approach can now be applied to patients with epilepsy receiving long-term treatment with CBZ and other anticonvulsants.