Efficacy of Topiramate as an add-on drug in seizures in Indian children--an observational study.

OBJECTIVE

To assess the efficacy of Topiramate as an add-on drug in the treatment of seizures in children of age group 0-12 years.

METHODS

Fifty children of age 0-12 years with seizures viz. partial seizures with or without secondary generalization, myoclonic jerks, infantile spasms, generalized tonic-clonic seizures, absence or mixed seizures were chosen from the out-patient department. Topiramate was added in small doses to conventional antiepileptics, and increased till the most effective/best-tolerated dose was reached. A Seizure Improvement Scale (SIS) was used. Outcome variables included seizure type, frequency, severity, SIS based on starting dose and the dose at the end of 6th month, EEG pattern, number of concomitant drugs used and adverse effects. Data was collected in monthly follow up visits for next 6 months (0-6 month study period). Details of seizures and medication availed by the study population during the 6 month period prior to the start of study were retrieved from available case records; this was used as control (-6 to 0 month study period). Using each of the outcome variables, efficacy was ascertained by clinical and statistical comparison.

RESULTS

Myoclonic jerks, generalized tonic clonic seizures, partial seizures with secondary generalization and complex partial seizures constituted 75% of seizures. Z-test for proportion showed significant reduction (p < 0.05) in these seizure types. ANOVA test for repeated measures (f = 162.3, p < 0.01) showed a significant fall in seizure frequency in 0 to 6 month period (t = 2.0, df = 49, p < 0.05) in seizure frequency. 50%, 18%, 8% and 10% of children had 100%, >75%, >50% and <50% reduction in seizure frequency, respectively at the end of 6 months. Statistically significant reduction in severity (status epilepticus) was found. An association between starting dose and position in the SIS was noted (Chi-square test); the authors recommend a starting dose of 1-2 mg/kg/day. Similarly, significant association between dose at the end of 6(th) month and position in the SIS was found; the authors recommend an optimum maintenance dose of 2.5-7.5 mg/kg/day. Though not statistically significant, the percentage of subjects using one concomitant antiepileptic drug (monotherapy) increased from 23% to 34%; those using 2 and 3 drugs (polytherapy) decreased from 40% to 34% and 33% to 27%, respectively. EEG pattern reverted back to normal in eight children. Apart from minor adverse effects, none had serious systemic manifestations during the study period.

CONCLUSIONS

The authors support the efficacy and safety of Topiramate as an add-on drug in seizures in children.