title: Topiramate titration and tolerability.
abstract: OBJECTIVE
  To evaluate the tolerability and efficacy of two titration rates for topiramate initiated as adjunctive therapy in adults with partial-onset seizures, with or without secondary generalization, in a multicenter, double-blindtrial.
  
  
  METHODS
  After a two-week baseline phase, 188 patients were randomized to either a 50/50 titration schedule (initial dosage 50 mg/d increased in 50-mg/d increments at weekly intervals; n = 95) or to a 100/200 titration schedule (initial dosage 100 mg/d increased by 100-200 mg/d at weekly intervals; n = 93). The maximum dosage of 400 mg/d was therefore achieved in eight weeks or three weeks, respectively.
  
  
  RESULTS
  Compared with the 100/200 titration rate, the 50/50 titration rate significantly reduced the cumulative incidence of treatment-emergent adverse events (TEAEs) leading to changes in topiramate therapy (ie., dosage reductions, interruptions or discontinuations of therapy) (p = 0.048) and significantly reduced treatment interruptions or withdrawals due to TEAEs (p = 0.040). Mild or moderate effects involving the central nervous system were the most frequent adverse events. At the final visit, therapeutic responses were comparable in the 50/50 and 100/200 titration groups: median percent seizure reduction was 42% vs. 33%, proportion of patients with 250% seizure reduction was 42% vs. 38%, and proportion of patients with no seizures during double-blind treatment was 14% vs. 10%, respectively. Seizure frequency was substantially reduced from baseline during topiramate titration. At day 22, with the 50/50 titration group receiving 150 mg/d and the 100/200 titration group receiving 400 mg/d, the mean percent seizure reduction was 51% and 54%, respectively.
  
  
  CONCLUSIONS
  Gradual initiation of topiramate therapy can significantly enhance patient tolerability without delaying therapeutic response.
authors.affiliation: Arkansas Epilepsy Program, Little Rock 72205, USA. aeprog@swbell.net
authors.forename: V
authors.initials: V
authors.lastname: Biton
authors.forename: K R
authors.initials: KR
authors.lastname: Edwards
authors.forename: G D
authors.initials: GD
authors.lastname: Montouris
authors.forename: J C
authors.initials: JC
authors.lastname: Sackellares
authors.forename: C L
authors.initials: CL
authors.lastname: Harden
authors.forename: M
authors.initials: M
authors.lastname: Kamin
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000097:blood* / Q000627:therapeutic use; D004311:Double-Blind Method; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D005632:Fructose / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077236:Topiramate
chemical_list: D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose