The effects of antiepileptic drugs оn cognitive functioning in adolescents with epilepsy

I.A. Martsenkovsky, I.I. Martsenkovska, T.O. Skrypnyk, H.V. Makarenko


Background. Current data suggest that antiepileptic medications such as phenobarbital, phenytoin, carbamazepine are associated with significant adverse cognitive effects, while stu-dies of topiramate and valproate showed conflicting results. At the same time, the positive effects of lamotrigine and levetiracetam on cognitive functioning in patients with epilepsy have been reported. The study purposed to evaluate the effects of the most commonly used antiepileptic drugs on cognitive functioning in adolescents with epilepsy. Materials and methods. Initially, 160 Ukrainian doctors working with adolescents suffering from epilepsy were interviewed in terms of their experience of using antiepileptic medications and possible associated effects on the cognitive functioning of adolescents with epilepsy. A prospective study was conducted in 58 adolescents with newly diagnosed epilepsy and prescribed monotherapy (carbamazepine, valproate, topiramate, levetiracetam, lamotrigine) and 11 adolescents with epileptic seizures uncontrolled by monotherapy with carbamazepine and valproate, who were prescribed polytherapy (carbamazepine with valproate or valproate with levetiracetam). All randomized adolescents were examined using Cambridge Neuropsychological Test Automated Battery before and every ten days after initiation of therapy with antiepileptic drugs in order to assess acute adverse cognitive effects. Additionally, Cogtest automated battery was used at the baseline, in 2 months of the study and after every month during 10 months since re-randomization to assess long-term cognitive impairment. Results. No acute disorders of cognitive functioning were found in adolescents treated with lamotrigine and levetiracetam in average therapeutic doses. One in two adolescents treated with valproate at a dose of 1,000 mg per day and those treated with carbamazepine demonstrated a significant impairment of cognitive functioning. The most frequent acute cognitive functioning impairment was observed in adolescents treated with carbamazepine at a dose of more than 600 mg per day and those on combined carbamazepine and valproate therapy. Adolescents treated with new antiepileptic drugs (lamotrigine and levetiracetam) in a wide range of doses did not demonstrate cognitive impairment after 12 months of treatment, while topiramate monotherapy was associated with cognitive impairment in certain patients. More than a half of adolescents treated with combined therapy (carbamazepine + valproate) demonstrated long-term cognitive functioning impairment. Long-term cognitive functioning impairment in adolescents treated with carbamazepine or valproate was dosage-dependent. Conclusions. Adolescents with epilepsy who received carba-mazepine, valproate or combined therapy of these drugs need to be closely monitored for possible short- and long-term cognitive functioning impairment. Adolescents on topiramate therapy need to be monitored for possible cognitive side effects at the dose titration stage. Therapy with levetiracetam and lamotrigine does not require monitoring of cognitive side effects.


antiepileptic drugs; acute cognitive functioning impairment; long-term cognitive functioning impairment; valproates; carbamazepine; levetiracetam; lamotrigine; topiramate


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