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

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 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.