Analysis of safety and tolerability data obtained from over 1,500 patients receiving topiramate for migraine prevention in controlled trials.
OBJECTIVE
Topiramate is an effective and generally well-tolerated migraine preventive therapy, as shown in three large, randomized, double-blind, placebo-controlled registration trials. Based upon efficacy/tolerability, topiramate 100 mg/day (50 mg BID) is the recommended target dose for most patients with migraine. To further assess the safety and tolerability of topiramate for migraine prevention, we analyzed safety data from 1,580 patients who participated in the three pivotal registration trials or an earlier pilot, randomized, double-blind, placebo-controlled trial.


METHODS
The safety population consisted of all patients who took >or=1 dose of study medication during the double-blind phase (topiramate 50 mg/day [N = 235], 100 mg/day [N = 386], 200 mg/day [N = 514], or placebo [N = 445]). Safety assessments included adverse event (AE) reports, physical examination, and clinical laboratory tests.


RESULTS
Paresthesia was the most common topiramate-associated AE (35%, 51%, and 49% of patients receiving topiramate 50 mg/day, 100 mg/day, or 200 mg/day, respectively [6% on placebo]). The most common topiramate-associated AE were generally mild or moderate in severity and occurred at consistently higher rates during the titration period, compared with the maintenance period of the double-blind phase. AEs leading to withdrawal from the recommended dose of topiramate 100 mg/day included paresthesia (8%), fatigue (5%), nausea (2%), and difficulty with concentration (2%). Serious AEs were infrequent, occurring in 2% of 1,135 topiramate-treated patients and 3% of 445 placebo-treated patients. Patients on topiramate experienced significant decreases in mean body weight compared with placebo.


CONCLUSIONS
Topiramate is generally safe and reasonably well tolerated for the prevention of migraine in adults. The most common topiramate-associated AEs were mild or moderate in severity and occurred more frequently during titration to target doses.
Adelman
James
J
Headache Wellness Center, Greensboro, North Carolina 27405, USA. jadelman@triad.rr.com
Freitag
Fred G
FG
Lainez
Miguel
M
Shi
Yingqi
Y
Ascher
Steven
S
Mao
Lian
L
Greenberg
Steven
S
Hulihan
Joseph
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004361:Drug Tolerance; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D008881:Migraine Disorders / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic; D012449:Safety; D000077236:Topiramate
D018696:Neuroprotective Agents; D000077236:Topiramate; D005632:Fructose