Effect of carbamazepine on psychomotor performance in näive subjects
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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.
Key wordscarbamazepine psychomotor function anticonvulsants epilepsy healthy subjects
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- Andrewes DB, Tomlinson L, Elwes RDC, Reynolds EH (1984) The influence of carbamazepine and phenytoin on memory and other aspects of cognitive function in new referrals with epilepsy. Acta Neurol Scand [Suppl] 99: 23–30Google Scholar
- Berry C, Gelder MG, Summerfield A (1965) Experimental analysis of drug effects on human performance using information theory concepts. Br J Psychol 56: 255–265Google Scholar
- Davidson DLW (1983) Anticonvulsant drugs. Br Med J 286: 2043–2045Google Scholar
- Dodrill CB, Troupin AS (1977) Psychotropic effects of carbamazepine in epilepsy: A double-blind comparison with phenytoin. Neurology 27: 1023–1028Google Scholar
- Frigerio A, Morselli PL (1975) Carbamazepine: Biotransformation. In: Perry JK, Daly DD (eds) Advances in neurology, vol. 11. Raven Press, New York, pp 295–308Google Scholar
- Hindmarch I (1980) Psychomotor function and psychoactive drugs. Br J Clin Pharmacol 10: 189–209Google Scholar
- Hoppener RJ, Kuyer A, Meijer JWA, Hulsman J (1980) Correlation between daily fluctuations of carbamazepine serum levels and intermittent side-effects. Epilepsia 21: 341–350Google Scholar
- Lesser RP, Pippenger CE, Luders H, Dinner DS (1984) High dose monotherapy in treatment of intractable seizures. Neurology (Cleveland) 34: 707–711Google Scholar
- Macphee GJA, Thompson GG, Scobie G, Agnew E, Park BK, Murray T, McColl KEL, Brodie MJ (1984) Effects of cimetidine on carbamazepine auto and hetero-induction in man. Br J Clin Pharmacol 18: 411–419Google Scholar
- Miller RG (1966) Simultaneous statistical inference. McGraw Hill, New York, pp 67–70Google Scholar
- Perucca E, Richens A (1981) Antiepileptic drugs: Clinical aspects. In: Richens A, Marks V (eds) Therapeutic drug monitoring. Churchill Livingstone, Edinburgh, pp 320–348Google Scholar
- Rapeport WG, Rogers KM, McCubbin T, Agnew E, Brodie MJ (1984) Treatment of intractable neurogenic pain with carbamazepine. Scott Med J 29: 162–166Google Scholar
- Reynolds EH (1983) Mental effects of anti-epileptic medication: A review Epilepsia 24 [Suppl 2]: S85-S95Google Scholar
- Riva R, Albani E, Ambrosetto G, Contin M, Cortelli P, Perucca E, Baruzzi A (1984) Diurnal fluctuations in free and total steady state plasma levels of carbamazepine and correlation with intermittent side-effects. Epilepsia 25: 476–481Google Scholar
- Rodin EA, Rim CS, Rennick PM (1974) The effects of carbamazepine on patients with psychomotor epilepsy: results of a double blind study. Epilepsia 15: 547–561Google Scholar
- Thompson PJ, Trimble MR (1982) Anticonvulsant drugs and cognitive functions. Epilepsia 23: 531–544Google Scholar
- Thompson PJ, Trimble MR (1983) Anticonvulsant serum levels: Relationship to impairments of cognitive functioning. J Neurol Neurosurg Psychiatry 46: 227–233Google Scholar