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Título

Evaluation of the minimum dose of sodium valproate with efficacy in seizure control in genetic generalized epilepsies

Resumo

More recently, the concern about teratogenic effects and abnormal neurodevelopment of the children of women with epilepsy using VPA motivated new studies comparing patients using low and high doses of valproate. The objective of this study was to provide criteria based on seizure control that allows establishing a cutoff dose of VPA that can be classified as a low dose in adults with genetic generalized epilepsies (GGE).
Our study is a cohort, retrospective, and observational that included patients with the clinical and electroencephalographic diagnosis of GGEs based on the ILAE criteria, later reclassified according to Hirsch et al., 2022.The patients were followed up at the epilepsy ambulatory of the Department of Neurology and Neurosurgery of the Federal University of São Paulo, Escola Paulista de Medicina, from 2003 to 2019. The institution's ethics committee approved the study. Patients with GGEs and at least two years of follow-up using sodium valproate/valproic acid in mono or polytherapy were included.
The following data were analyzed: type of epileptic syndrome, clinical data related to epilepsy, formulation, and dose of VPA, besides ASMs used in association. Adverse effects and use during pregnancy were also observed. Seizure control was classified according to Prasad et al.
Of the total of 225 patients evaluated, 115 were on monotherapy with VPA and 110 on polytherapy, including VPA. The only cutoff capable of distinguishing the groups was that of patients using doses up to 1000 mg/day (Fisher; p=0.006), with 88% of cases with good control using doses up to this value against only 50% of cases with poor control. Evaluating patients on polytherapy, no cutoff was able to separate the seizure control groups (Fisher, p≥0.05). Concerning polytherapy, no specific combination of ASMs with VPA could distinguish cases with good control from those with poor seizure control (Logistic Regression, p=0.051). On women with good seizure control, those with childbearing age took VPA doses with a median of 600 mg/day, while the others used doses with a median of 1000 mg/day (Mann-Whitney, p=0.036).
The minimum dose that adequately separates patients into good and poor seizure control is 1000 mg/day, which should be used as a cutoff in studies that assess the difference in effects between the therapeutic ranges. About women of childbearing age, it was observed that they used lower doses than other women in cases of good seizure control.

Área

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