The efficacy and side effects of topiramate on refractory epilepsy in infants and young children: a multi-center clinical trial.

OBJECTIVES: This study has been conducted to assess the efficacy and safety of topiramate in refractory epilepsies in infants and young children. METHODS: A prospective clinical trial was performed in three tertiary care hospitals, on 47 children aged 6-60 months with refractory epilepsy. Topiramate was added to at least two baseline anti-epileptic drugs. The efficacy was rated according to seizure type, frequency and duration. RESULTS: Children with refractory epilepsy were classified according to their clinical, neuro-imaging, and neurophysiological profile into infantile spasms (IS) (9 cases, 19%), Lennox-Gastaut syndrome (LGS) (25 cases, 53%) and other epilepsies (13 cases, 28%). Children were also classified into cryptogenic and symptomatic epilepsy. Topiramate was introduced as add-on therapy in a daily dose of 1 mg/kg/day for 2 weeks, followed by increments of 1-3 mg/kg/day at 2-week intervals, up to a maximum of 10 mg/kg/day. After a minimum treatment period of 6 months, 28 (60%) of the children had a satisfactory response (completely seizure free, or more than a 50% seizure reduction). The remaining 19 children (40%) had an unsatisfactory response (50% or less reduction in seizure frequency, no change or increased seizure frequency). Topiramate appeared to be equally effective in infantile spasms, Lennox-Gastaut syndrome and children with other types of epilepsy, with no significant difference between those with a satisfactory and an unsatisfactory response (p=0.089). There was also no significant difference in response between patients with cryptogenic and symptomatic epilepsy (p=0.360). Mild to moderate adverse effects, mainly somnolence, anorexia and nervousness, were present in 25 (53%) of children. One of the children developed hypothyroidism. CONCLUSION: Although the long term safety and possible adverse effects of topiramate have not been fully established in infants and young children, this study has shown that it is a useful option for children with frequent seizures unresponsive to standard anti-epileptic drugs.