The Effects on Cognitive Function and Behavioral Problems of Topiramate Compared to Carbamazepine as Monotherapy for Children with Benign Rolandic Epilepsy

Abstract

Summary:Purpose: To evaluate the cognitive and behavioral effects of topiramate (TPM) versus carbamazepine (CBZ) using efficacious doses of each drug as monotherapy for children with benign rolandic epilepsy.Methods: A multicenter, randomized, open-label, observerblinded, parallel-group clinical trial was conducted. TPM was introduced at a dose of 12.5 mg/day with the minimum target dose of 50 mg/day in patients <30 kg and 75 mg/day in patients >30 kg over 4 weeks. CBZ was started at a dose of 10 mg/kg/day with the minimum target dose of 20 mg/kg/day over 4 weeks. Additional individual escalation was allowed up to a maximum target dose. The primary study end point was change on a neuropsychological test battery after 28 weeks of treatment.Results: Neuropsychological data were available for 88 patients (45 patients for TPM and 43 patients for CBZ). Of the cognitive variables measured, arithmetic showed significant worsening in TPM (p = 0.037). An additional test, for maze, also showed a significantly greater improvement for CBZ (p = 0.026). Of behavioral variables, no significant changes were found but the scores had a negative trend for the TPM. When 30 patients on the minimum target dose for TPM were compared to 40 patients treated with minimum target CBZ, there was no significant worsening of cognitive and behavioral effects in the TPM.Conclusion: The pattern of neuropsychometric changes with TPM seemed to be slightly worse overall than CBZ. However, outcome with the minimum target dose did not differ significantly in comparisons between the treatment groups.

The cognitive impact of antiepileptic drugs

“…A double-blind trial reported deterioration in measures of information processing speed and attention [Wesnes et al 2009]. Other studies report poorer verbal fluency in adults with partial seizures than in control subjects [Aikiä et al 2006], detrimental effects on memory [Shehata et al 2009;Forsythe et al 1991], worse arithmetic performance [Kang et al 2007] and faster motor skills after discontinuation [Duncan et al 1990]. Impaired movement time, reaction time, finger tapping rate and number cancellation were seen in one study, but these effects remitted by 1 month after treatment commencement [Larkin et al 1992].…”

Safety and Tolerability of Antiepileptic Drug Treatment in Children with Epilepsy

“…Open-label studies indicate that OXC monotherapy had no impact on cognitive function and intelligence over 6 months in children and adolescents with newly diagnosed partial-onset seizures, [126] whereas the cognitive effects of TPM over 28 weeks were slightly worse than those of CBZ in children with benign rolandic epilepsy. [127] A retrospective analysis of long-term use of LEV and TPM showed that cognitive adverse effects in children and adults with epilepsy were more common with TPM than with LEV and more frequently led to drug withdrawal. [128] Amongst children and adults treated with LEV, a minority can develop acute psychosis consisting of visual or auditory hallucinations and delirium within the first few weeks of treatment.…”

Topiramate on the quality of life in childhood epilepsy

“…NS, not significant (P > 0.05). majority of children, without significant cognitive or behavioral side effects [21]. Furthermore, we showed that TPM therapy was associated with an improved QOL.…”

“…Cognitive and behavioral impairment, caused by AEDs and consequently low QOL may be of particular concern for children in whom adverse effects during neurodevelopment may have long-lasting consequences. TPM has cognitive side effects, but these can be reduced by adjusting the drug dose and rate of escalation [21]. The changes at low TPM doses were well tolerated in the Scores are on a scale of 0-100 points, with higher scores indicating better quality of life.…”