Long-term effectiveness and tolerability of topiramate in children with epilepsy under the age of 2 years: 4-year follow-up

Abstract

This is a long-term, open label, observational study aimed to broaden our clinical experiences in managing infants and toddlers with epilepsy. The long-term retention rate and side effects of topiramate (TPM) in them were evaluated and compared with carbamazepine (CBZ). A total of 146 children were involved in the study (TPM=41, CBZ=105). The retention rates at 24 , 36, and 48 months were 46.3%, 34.1%, 26.8% for TPM and 36.2%, 23.8%, 13.3% for CBZ, respectively. At 6 months after starting antiepileptic drugs (AED), the seizure freedom or clinical efficacy (seizure reduction rate more than 50 percent) were 73.2% for TPM and 62.9% for CBZ. The major side effects led to discontinuation included psychomotor slowing, poor oral intake from TPM and sleepiness and skin rash from CBZ. TPM was discontinued due to side effects in one case (2.4%) and lack of efficacy in five cases (12.2%), whereas CBZ was discontinued due to lack of efficacy (22.9%) and side effects (6.7%). As compared with CBZ, TPM showed the same long-term retention rate in children under the age of 2 yr, and no serious side effects. It is therefore concluded that TPM can be considered as a major AED for treating children with epilepsy under the age of 2 yr.

Keywords: Adverse Effects; Carbamazepine; Topiramate; Treatment Outcome.

Fig. 1

Proportion of patients stayed on the initial AED at 24, 36, and 48 months. In the CBZ group, the proportion of patients kept on CBZ was 40.4%, 26.6%, and 14.9% at 24, 36, 48 months, respectively, and 47.7%, 31.8%, and 25.0% in the TPM groups. TPM tends to be continued in higher proportion of patients, but is not statistically different from CBZ. CBZ, carbamazepine; TPM, topiramate; AED, antipileptic drug.

Fig. 2

Cumulative survival of topiramate (TPM) and carbamazepine (CBZ). The retention rates of TPM and CBZ were compared over 48 months or longer. TPM seemed to have a better retention rate, but was not significantly different from CBZ.

Fig. 3

Comparative efficacy between CBZ and TPM. At 6 months after starting the antiepileptic drug, 58.5% in the TPM group and 54.3% in the CBZ group became seizure free and the average monthly seizure frequency was decreased by 50% or more in 14.6% of the TPM group and 8.6% of the CBZ group respectively. The findings suggest that TPM is as efficacious as CBZ. Grade A, seizure freedom; Grade B, seizure reduction of average monthly frequency ≥50%; Grade C, seizure reduction of average monthly frequency 25-50%; Grade D, seizure reduction of average monthly frequency ≤25%; Grade E, no improvement in seizures; Grade F, worsening of seizures. CBZ, carbamazepine; TPM, topiramate; AED, antipileptic drug.

Fig. 4

Adverse events of TPM (A) and CBZ (B). There were 12 events of side effects in 10 of 41 patients treated with TPM. In CBZ treated patients, there were 21 events of side effects in 18 of 105 patients. The most common adverse events were CNS-related in both groups and anhidrosis was another noticeable adverse event in the TPM group. CBZ, carbamazepine; TPM, topiramate.

Fig. 5

The main reason of discontinuation of AEDs. The leading causes were lack of efficacy (12.2% for TPM, 22.9% for CBZ) and adverse events (2.4% for TPM, 6.7% for CBZ). Others included deaths from acute illnesses, the poor compliance and so on. No statistically significant difference was noted between two groups. CBZ, carbamazepine; TPM, topiramate; AED, antipileptic drug.