Clobazam higher-evening differential dosing as an add-on therapy in refractory epilepsy

Abstract Purpose Clobazam treatment tailored to the timing of patient's seizures may improve seizure control. We aim to describe the safety and efficacy of higher-evening differential dose of clobazam as add-on therapy in patients with night-time/early morning seizures. Methods Differential dos...

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Bibliographic Details
Published in:Seizure (London, England) England), 2016-08, Vol.40, p.1-6
Main Authors: Thome-Souza, Sigride, Klehm, Jacquelyn, Jackson, Michele, Kadish, Navah E, Manganaro, Sheryl, Fernández, Iván Sánchez, Loddenkemper, Tobias
Format: Article
Language:English
Subjects:
Anticonvulsants - administration & dosage
Anticonvulsants - adverse effects
Anticonvulsants - pharmacology
Benzodiazepines - administration & dosage
Benzodiazepines - adverse effects
Benzodiazepines - pharmacology
Case-Control Studies
Child
Child, Preschool
Chrono-epileptology
Clobazam
Differential dosing
Drug Chronotherapy
Drug Resistant Epilepsy - drug therapy
Drug Therapy, Combination
Female
Humans
Male
Neurology
Outcome Assessment (Health Care)
Refractory epilepsy
Retrospective Studies
Seizures - drug therapy
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Summary:Abstract Purpose Clobazam treatment tailored to the timing of patient's seizures may improve seizure control. We aim to describe the safety and efficacy of higher-evening differential dose of clobazam as add-on therapy in patients with night-time/early morning seizures. Methods Differential dosing with higher evening dosing was started based on a high proportion of seizures (> 80%) at nighttime (6 p.m. to 6 a.m.). Differential dosing was defined as providing more than 50% of the total daily dose of clobazam after 6 pm. Results Twenty-seven patients were treated with clobazam differential dosing as an add-on therapy. The median age was 9.1 years, with 11 (40.7%) females and median of the first follow-up was 2.7 months. Patients with differential dosing tolerated a higher median total clobazam dose of 0.8 mg/kg/d at first follow-up, as compared to 0.6 mg/kg/d in controls. In differential dose, the median percentage of the total clobazam dose administered in the evening was 66.7%. Differential dose patients exhibited a median seizure reduction of 75% as compared to 50% in controls ( p < 0.005). Patients with generalized seizures benefited the most from differential dosing with a 77.5% median seizure reduction, as compared to 50% in controls ( p = 0.017). Conclusion Higher-evening differential dose of clobazam improved seizure control in patients with predominantly nighttime and early-morning seizures. Chronotherapy tailored to the patients’ seizure susceptibility patterns may improve care in epilepsy patients as differential dosing may allow for higher overall treatment doses at times of greatest seizure susceptibility without increased side effects at other times.
ISSN:1059-1311
1532-2688
DOI:10.1016/j.seizure.2016.05.014