Randomised controlled trial to assess acceptability of phenobarbital for childhood epilepsy in rural India

Abstract

Background: The use of phenobarbital for childhood epilepsy is controversial because of reported behavioural side-effects; however, whether this research can validly be extrapolated to developing countries is not clear. We undertook a randomised comparison of phenobarbital and phenytoin to assess the acceptability and efficacy of phenobarbital as monotherapy for childhood epilepsy in rural India.

Methods: Between August, 1995, and February, 1996, 109 unselected children aged 2-18 years with partial and generalised tonic-clonic epilepsy were identified by population screening. 15 families declined to take part. 94 children were randomly allocated treatment with phenobarbital (1.5 mg/kg daily for 2 weeks; maintenance dose 3.0 mg/kg daily; n = 47) or phenytoin (2.5 mg/kg daily then 5.0 mg/kg daily; n = 47). Children were followed up for 12 months. The primary outcome measure was the frequency of behavioural side-effects; behaviour was assessed by the Conners parent rating scale for children aged 6 years and older, and by the preschool behaviour screening questionnaire (BSQ) for those aged 2-5 years, at 12 months or at withdrawal from treatment. Analysis was by intention to treat.

Findings: The mean log-transformed scores on the behaviour rating scales did not differ significantly between the phenobarbital and phenytoin groups (Conners 2.64 [SD 0.71] vs 2.65 [0.89], p = 0.97; n = 32 in each group: BSQ 2.12 [1.31] vs 2.18 [1.02], p = 0.94; n = 4 vs 3). The odds ratio for behavioural problems (phenobarbital vs phenytoin) was 0.51 (95% CI 0.16-1.59). There was no excess in parental reports of side-effects for phenobarbital. We found no difference in efficacy between the study drugs (adjusted hazard ratio for time to first seizure from randomisation 0.97 [0.28-3.30]).

Interpretation: This evidence supports the acceptability of phenobarbital as a first-line drug for childhood epilepsy in rural settings in developing countries.

PIP: The acceptability and efficacy of phenobarbital treatment for childhood epilepsy was evaluated in 94 children from rural India with partial and generalized tonic-clonic epilepsy. Children were randomly assigned to receive wither 1.5 mg/kg of phenobarbital daily for 2 weeks, followed by a maintenance dose of 3.0 mg/kg daily, or 2.5 mg/kg daily of phenytoin, followed by a maintenance dose of 5.0 mg/kg daily for a total of 12 months. Behavioral side effects were assessed through use of the Conners parent rating scale for children 6 years of age and above and by the preschool behavioral screening questionnaire for younger children. The mean log-transformed scores on the behavior rating scales did not differ significantly between the phenobarbital and phenytoin groups. The frequency of behavioral problems was 30% in both treatment groups. The odds ratio for behavioral problems in the phenobarbital versus phenytoin groups was 0.51 (95% confidence interval, 0.16-1.59). Behavioral problems were more common among children with cerebral impairments, those under 5 years of age, and girls. Both study drugs were equally effective and 65% of children were seizure-free in the final quarter of treatment. These findings suggest that concerns about phenobarbital-related behavioral side effects may not be valid in developing countries and that this drug is an effective, acceptable anti-epileptic for rural Indian children.