Search

A recent United Kingdom cost minimization analysis (CMA) of four antiepileptic drugs (AEDs) used to treat newly diagnosed adult epilepsy demonstrated that a new drug, lamotrigine (LTG), incurred higher costs than carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA), whose costs were similar. This analysis took account of each drug's side-effect and tolerability profile. The present analysis investigated the costs of treatment with LTG, CBZ, PHT, and VPA in 12 European countries. Data were derived from published sources and from a panel of locally based experts. When no published data were available, estimates were obtained using expert opinion by a consensus method. These data were incorporated into a treatment pathway model, which considered the treatment of patients during the first 12 months after diagnosis. The primary outcome considered was seizure freedom. Randomized controlled trials demonstrate that the drugs considered are equally effective in terms of their ability to achieve seizure freedom, and thus the most appropriate form of economic evaluation is a CMA. These trials provided data on the incidence of side effects, dosages, and retention rates. The economic perspective taken was that of society as a whole and the analysis was calculated on an "intent-to-treat" basis. Only direct medical costs were considered. In each country considered, LTG was twofold to threefold more expensive than the other drugs considered. A sensitivity analysis demonstrated that varying each of the assumptions (range defined by expert panels) did not significantly alter the results obtained.

A previous suggestion that antiepileptic drugs may induce color vision deficiencies prompted us to examine whether color vision deficiencies may occur at lower drug serum concentrations than those associated with symptoms of neurotoxicity. Eighty patients presenting with epilepsy received monotherapies of valproic acid, phenytoin, or carbamazepine; 18 patients did not receive antiepileptic drug therapy. Color vision was tested by the Farnsworth-Munsell 100-hue test, spectral sensitivity, and the newly developed tritan screening plates. Patients treated with phenytoin or carbamazepine developed blue-yellow color vision deficiencies. In contrast, patients exposed to valproic acid or receiving no drug treatment showed normal color vision. There was a significant correlation (p < 0.0001) between signs of neurotoxicity induced by phenytoin or carbamazepine and blue-yellow color vision deficiencies. In contrast, we found no correlation between these signs of neurotoxicity and the drug serum concentrations (p = 0.0637). Color vision testing in epileptic patients treated with phenytoin or carbamazepine appears to be a sensitive method for early detection and monitoring of clinical neurotoxicity.

Advanced psychophysical tests, performed in 42 patients who have seizures, showed that the widely used antiepileptic drugs, diphenylhydantoin and carbamazepine, can specifically affect retinal function, while valproic acid and the epileptic seizures do not. The Farnsworth-Munsell 100-Hue and Panel D-15 désaturé tests revealed an accumulation of errors along the tritan/tetartan axis and a high total error score. As shown by measurement of the so-called transient tritanopia and by determination of the spectral sensitivity, this blue vision defect is not only due to loss of postreceptoral interaction between long- and short-wavelength-sensitive cones, but is also based on a disturbance in the receptor mechanism itself. The dark adaptation curve was not affected. As determined by cone flicker thresholds during dark adaptation, the inhibitory action of rods on cones is reduced. The results obtained for mesopic vision and especially glare sensitivity measured by nyktometry were markedly affected in these patients compared to the normal population. The psychophysical methods provide a very sensitive test for early detection of drug-induced retinal dysfunction and allow clear differentiation between the loss of a receptor mechanism and a defect in the neuronal interaction between photoreceptors in the human visual system induced by antiepileptics.

Advanced psychophysical tests, performed in 42 epileptic patients, show that the antiepileptic drugs phenytoin and carbamazepine can specifically affect the retinal function, while Valproic Acid and the epileptic seizures do not. The Farnsworth-Munsell 100-Hue and Panel D-15 désaturé tests revealed an accumulation of errors along the tritan/tetartan axis (blue colour vision deficiencies) and a high total error score. The same defect was shown by measurement of the spectral sensitivity functions. The results obtained for mesopic vision and especially glare sensitivity measured by nyktometry were markedly affected in these patients compared to a normal population. The enhanced sensitivity to glare is mainly the only one symptom complained by the patient. We propose a screening method for early detection of phenytoin- and carbamazepine-induced neurotoxicity. The literature of ocular side effects of anticonvulsant drugs is carefully reviewed.