The
antiepileptic effect, effects on EEG, and tolerability of
taltrimide, a new
taurine derivative, were studied in this open clinical trial in 27 patients with severe
epilepsy resistant to conventional drugs. After the 2-week control phase,
taltrimide was given in gradually increasing doses up to 4.0 g/day--this dose used for 12 days.
Taltrimide was given over 4 weeks and it was gradually withdrawn over 2 weeks. The frequency of
seizures increased statistically significantly during the trial with increasing dose of
taltrimide and decreased again in the withdrawal phase of the trial. Of six dropouts, one had
status epilepticus, and in two patients increased number or severity of
seizures necessitated withdrawal of
taltrimide. There were no changes in EEG recordings or in laboratory data for safety evaluation.
Taltrimide penetrated well through the blood-brain barrier, with the concentration of its main metabolite, phthalimidoethanesulphonamide, in cerebrospinal fluid, about half that in serum. The concentration of
phenytoin increased statistically significantly, and there was a significant decrease in serum
carbamazepine concentration during the
taltrimide treatment. The anticonvulsive effect of
taltrimide observed in animal experiments could not be confirmed in this study; in contrast, the
seizures increased statistically significantly during
taltrimide treatment. The reason for this remains obscure. The doses used, the significant drug interactions, or the patient material seemingly do not explain totally the noticed increase in seizure frequency. One explanation may be that
taltrimide has proconvulsive properties in humans.