Time course of adverse events most commonly associated with topiramate for migraine prevention.
The efficacy, safety and tolerability of topiramate has been demonstrated in three large multicenter, randomized, double-blind, placebo-controlled trials. To characterize the time course of adverse events (AEs) that led to treatment discontinuation in >/=2% of patients who received topiramate 100 mg/day during three pivotal, multicenter, randomized, double-blind, placebo-controlled, and 26-week trials. The pooled population comprised all randomized patients who reported safety data during the double-blind phase (topiramate 100 mg/day, n = 386; placebo n = 372), which consisted of a 4-week titration period and a 22-week maintenance period. Incidence, time to onset, and cumulative mean rate of AEs were assessed. Overall, AEs led to treatment discontinuation in 24.9% of patients receiving topiramate 100 mg/day and 11.0% receiving placebo (P < 0.001). AEs leading to discontinuation during the double-blind phase in > or =2% of patients included paresthesia (8.0% discontinued), any cognitive symptoms (7.3% discontinued), fatigue (4.7% discontinued), insomnia (3.4% discontinued), nausea (2.3% discontinued), loss of appetite, anxiety, and dizziness (2.1% discontinued because each AE). Most AEs began during the titration period. Paresthesia, any cognitive symptoms, nausea, and loss of appetite occurred at a higher rate in the topiramate group than in the placebo group (P < 0.01). AEs leading to discontinuation of topiramate are probably to occur during dose titration. If a patient has not experienced one of these AEs within the first 6 weeks of initiating topiramate 100 mg/day, these AEs are unlikely to occur.
University Clinic Hospital, University of Valencia, Valencia, Spain. jlaineza@meditex.es
M J A
MJ
Láinez
F G
FG
Freitag
J
J
Pfeil
S
S
Ascher
W H
WH
Olson
S
S
Schwalen
D000328:Adult; D000855:Anorexia / Q000139:chemically induced; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D003072:Cognition Disorders / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D009325:Nausea / Q000139:chemically induced; D010292:Paresthesia / Q000139:chemically induced; D010349:Patient Compliance; D010919:Placebos; D013995:Time; D013997:Time Factors; D000077236:Topiramate; D028761:Withholding Treatment
D000927:Anticonvulsants; D010919:Placebos; D000077236:Topiramate; D005632:Fructose