Carbamazepine and phenytoin in epilepsies refractory to barbiturates: efficacy, toxicity and mental function.

A group of 51 patients with chronic cryptogenic or symptomatic localized epilepsy refractory to therapy with barbiturates underwent progressive substitution with phenytoin or carbamazepine, in standardized and randomized fashion. After drug changes were completed two thirds of the patients remained seizure free during a period of 6 months. A clearer effect of phenytoin and carbamazepine was seen on secondary generalized than on partial seizures. The frequency of severe side effects decreased after the change to phenytoin and carbamazepine. The group on carbamazepine improved in immediate and late recall, and in immediate and late recognition of pictures. The group on phenytoin improved significantly in the Stroop test. Patients changed to phenytoin, but not those changed to carbamazepine, became significantly more aggressive, anxious and depressive than when on phenobarbital, as measured by subjective scales. The results indicate that patients should not be considered refractory to antiepileptic drug therapy while on barbiturates. Cognitive dysfunction and mood changes observed in epilepsy may be temporary and dependent on the presence of seizures and/or on use of barbiturates.

Cognitive functions, epileptic syndromes and antiepileptic drugs.

Cognitive function of patients on monotherapy specific for their epileptic syndrome has been studied infrequently. We evaluated 7 patients with symptomatic localised epilepsies (SEL) on phenytoin aged 30 +/- 12 (mean +/- standard deviation) years, 8 with idiopathic generalised epilepsies on sodium valproate aged 18 +/- 4 years, 16 with SEL on carbamazepine aged 28 +/- 11 years, and 35 healthy controls aged 27 +/- 11 years. All subjects were of normal intelligence, educated appropriately to age, and led productive lives in the community. Two of the patients on carbamazepine and one on valproate had less than five partial, absence or myoclonic seizures monthly, the remaining were controlled. Carbamazepine serum concentrations were 12 +/- 5 micrograms/ml, phenytoin were 23 +/- 7, and valproate were 62 +/- 23 (mean +/- sd). Tests included immediate recall and recognition for pictures, Stroop test, delayed recall and recognition of pictures. Patients on phenytoin and valproate performed significantly worse than controls on immediate recall, and patients on carbamazepine performed significantly worse than controls in Stroop test (p < 0.01). The results indicate relatively minor effects of the epileptic syndromes and of phenytoin, carbamazepine and valproate on cognition of patients with controlled epilepsy leading productive lives in the community. We conclude that the cognitive deficit found in chronic epileptic patients on poly-therapeutic drug regimen must be multifactorial, and that future studies need to control for all possible variables in order to achieve meaningful results.

Cognitive functions of epileptic patients on monotherapy with phenobarbitone and healthy controls.

Quantitative measurements have indicated that heredity, cerebral damage, psycho-social aspects, ictal and inter-ictal phenomena and antiepileptic drugs may interfere in the cognitive dysfunction of epileptic patients. In the present study objective methods included immediate and late recall and recognition of pictures, Stroop test and auditory selection. Twenty patients with symptomatic localized epilepsy aged 17-52 years (27 +/- 10, mean +/- sd) were compared to age and socially matched healthy controls. Patients were on therapeutic serum concentrations (25 +/- 12 mu/ml) of phenobarbitone and had active epilepsy with 1.94 generalized tonic-clonic, 0.85 simple partial and 6.28 complex partial seizures monthly (means). Patients performed worse than controls in all 6 tests (p less than 0.05 to p less than 0.001), indicating a generalized cognitive deficit related to seizures and/or barbiturate therapy. We suggest further studies should be carried out in populations with uniform monotherapeutic regimens and epileptic syndromes in order to isolate factors related to the cognitive dysfunction of epileptic patients.