title: [Slow release versus immediate release oxcarbazepine in difficult-to-treat focal epilepsy: a multicenter, randomized, open, controlled, parallel group phase III study].
abstract: BACKGROUND
  The aim of the study was an assessment of the tolerability and efficacy of slow release oxcarbazepine (OXC-MR) versus immediate release OXC (OXC-IR) after forced titration in patients with focal epileptic seizures with and without secondary generalization who had previously not become seizure-free under OXC-IR with or without concomitant antiepileptic drugs. The primary study variable was to assess the maximum tolerated dosage with OXC-MR and OXC-IR.
  
  
  METHODS
  This was designed as a multicenter, randomized, open, controlled, parallel group phase III study. After randomization patients received OXC-MR or OXC-IR for a study period of 26 days. The initial dosage of 900 mg, 1,200 mg or 1,500 mg OXC was increased every 5 days by 300 mg up to a maximum daily dosage of 2,700 mg. In cases of intolerable adverse events dosage could be reduced by 150 mg 2 days after an increase. Adverse events and executive abilities were assessed with the questionnaire "Adverse Event Profile plus" and with the Epitrack® test protocol. Serum concentrations of OXC and its active metabolite were measured in a part of the patient group.
  
  
  RESULTS
  The 71 patients (54% male, age: 19-70 years) enrolled in the study were randomized. The maximum mean daily OXC dosage at the end of the study period was 1,950 mg with OXC-MR and thus statistically significantly higher than in OXC-IR group (1,650 mg, p = 0.022). The number of causally related adverse events was lower in the OXC-MR group (n = 104 versus n = 138 with OXC-IR) and CNS-related adverse events such as dizziness, tremor, somnolence and headache occurred significantly less often with OXC-MR (OXC-MR 65.7%, OXC-IR 88.9%, p = 0.01). Fluctuations of serum concentrations of the active metabolite were less pronounced under the OXC-MR regimen.
  
  
  CONCLUSIONS
  Due to better tolerability OXC-MR allowed higher maintenance dosages to be reached than OXC-IR. In spite of a higher mean daily dosage adverse events and especially CNS-related adverse events occurred less often than with OXC-IR.
authors: Epilepsiezentrum Kork, Landstr. 1, 77694 Kehl, Deutschland. bsteinhoff@epilepsiezentrum.de
authors: B J
authors: BJ
authors: Steinhoff
authors: H
authors: H
authors: Stefan
authors: A
authors: A
authors: Schulze-Bonhage
authors: R
authors: R
authors: Hueber
authors: W
authors: W
authors: Paulus
authors: M
authors: M
authors: Wangemann
authors: C E
authors: CE
authors: Elger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage; D002220:Carbamazepine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004828:Epilepsies, Partial / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D000078330:Oxcarbazepine; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D002220:Carbamazepine; D000078330:Oxcarbazepine