Abstract
In a recent NIH-sponsored parallel-group placebo-controlled blinded study of flunarizine for the treatment of partial-onset seizures, the flunarizine serum concentration was controlled to a constant level among patients in order to reduce response variability. Flunarizine was found to exhibit modest anti-epileptic efficacy. A potential criticism of this study is that the chosen controlled concentration was too low to determine optimal efficacy.
As a participating center in this study we investigated the effect of higher doses of open-label flunarizine on seizure frequency in 16 patients with refractory partial seizures. Following the completion of the blinded placebo/flunarizine phase, all patients were initiated at the flunarizine dose calculated to result in a serum concentration of 60 ng·ml−1. The dose was subsequently increased each 8–12 weeks to a maximum of 2.7 times the initial dose.
On the initial maintenance flunarizine dose, seizure control was improved, with an average seizure reduction of 47% compared to pre-blinded-phase baseline. When higher doses were administered, adverse reactions were more common yet improved seizure control did not occur in most patients.
These findings complement those of the concentration-controlled NIH study and suggest that appropriate flunarizine doses were utilized in that study.
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Handforth, A., Mai, T. & Treiman, D.M. Rising dose study of safety and tolerance of flunarizine. Eur J Clin Pharmacol 49, 91–94 (1995). https://doi.org/10.1007/BF00192365
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DOI: https://doi.org/10.1007/BF00192365