Topiramate, Carbamazepine, and Valproate Monotherapy: Double-Blind Comparison in Children With Newly Diagnosed Epilepsy

Abstract

In a novel double-blind trial, topiramate was compared with the investigator's choice of carbamazepine or valproate as first-line therapy in patients as young as 6 years of age with newly diagnosed epilepsy. Among 613 patients enrolled in the trial, 119 (19%) were children or adolescents (6-16 years of age). No differences between fixed doses of topiramate (100 and 200 mg/day) and carbamazepine (600 mg/day) or valproate (1250 mg/day) were observed in efficacy measures: time to exit, time to first seizure, and the proportion of patients who were seizure free during the last 6 months of treatment. Topiramate 100 mg/day (2.0 mg/kg/day in this study population) was associated with the fewest discontinuations owing to side effects. Based on efficacy and tolerability, the recommended target dose for topiramate as first-line therapy in children and adolescents is 100 mg/day.

Topiramate for the treatment of epilepsy and other nervous system disorders

“…However, since the estimated topiramate clearance is increased in the presence of enzyme induction, initial monotherapy topiramate doses should most likely be even lower, as already demonstrated by Gilliam and colleagues [42]. Also, efficacy of these doses has been established as equivalent to traditional first-line therapy in a noninferiority study comparing 100 and 200 mg/day of topiramate to the clinician's choice of either 600 mg/day of carbamazepine or 1250 mg/day of valproic acid [43].…”

Umstellung von Carbamazepin oder Oxcarbazepin auf Topiramat bei Jugendlichen und Erwachsenen mit Epilepsie

“…n Behandlung Es wurde empfohlen, die Behandlung mit Topiramat (Topamax®) entsprechend der Fachinformation einzuleiten; diese empfiehlt zu Therapiebeginn eine TPM-Dosierung von 25 mg/Tag jeweils abends, welche dann zunächst bis 50 mg 2 × täglich (morgens und abends) auftitriert wird [13,20]. Dabei richtete sich die Titrationsgeschwindigkeit jeweils nach dem Ansprechen der Patienten auf die TPM-Therapie.…”

“…At the study endpoint, the intended shift to TPM monotherapy was achieved in 73% of patients at a median TPM dose of 100 mg/d. A seizure reduction of ≥ 50% was achieved in 91% of patients in the last scheduled period (weeks [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]; 62% of patients entering that period remained seizure free. Quality of life at the endpoint improved significantly when compared with baseline for all domains of QOLIE-10 (P < 0.001).…”

“…Topiramat (Topamax®, Janssen-Cilag GmbH, Neuss) ist auf Grund seiner erwiesenen Wirksamkeit bei Patienten mit neu diagnostizierter wie auch mit refraktärer Epilepsie zur Anwendung in der Zusatzoder Monotherapie bei Kindern und Erwachsenen zugelassen [13][14][15][16][17]. Angesichts der geringen pharmakokinetischen Wechselwirkungen, seiner guten Verträglichkeit und seines breiten antikonvulsiven Wirkungsspektrums [15,[18][19][20][21][22] ist Topiramat (TPM) auch für die Ersttherapie eine viel versprechende Option.…”

Therapeutic Efficacy of Antiepileptic Drugs

“…Only a few comparative trials have been conducted in newly diagnosed childhood epilepsy with multiple antiepileptic drugs (Table 10.8) [15][16][17][18][19][20][21][22]. These have been typically conducted in children with partial-onset seizures or secondary generalized seizures that are cryptogenic or symptomatic in etiology.…”