BACKGROUND: Which medication, if any, to use to prevent the headache of 
pediatric migraine has not been established.
METHODS: We conducted a randomized, double-blind, placebo-controlled trial of 
amitriptyline (1 mg per kilogram of body weight per day), topiramate (2 mg per 
kilogram per day), and placebo in children and adolescents 8 to 17 years of age 
with migraine. Patients were randomly assigned in a 2:2:1 ratio to receive one 
of the medications or placebo. The primary outcome was a relative reduction of 
50% or more in the number of headache days in the comparison of the 28-day 
baseline period with the last 28 days of a 24-week trial. Secondary outcomes 
were headache-related disability, headache days, number of trial completers, and 
serious adverse events that emerged during treatment.
RESULTS: A total of 361 patients underwent randomization, and 328 were included 
in the primary efficacy analysis (132 in the amitriptyline group, 130 in the 
topiramate group, and 66 in the placebo group). The trial was concluded early 
for futility after a planned interim analysis. There were no significant 
between-group differences in the primary outcome, which occurred in 52% of the 
patients in the amitriptyline group, 55% of those in the topiramate group, and 
61% of those in the placebo group (amitriptyline vs. placebo, P=0.26; topiramate 
vs. placebo, P=0.48; amitriptyline vs. topiramate, P=0.49). There were also no 
significant between-group differences in headache-related disability, headache 
days, or the percentage of patients who completed the 24-week treatment period. 
Patients who received amitriptyline or topiramate had higher rates of several 
adverse events than those receiving placebo, including fatigue (30% vs. 14%) and 
dry mouth (25% vs. 12%) in the amitriptyline group and paresthesia (31% vs. 8%) 
and weight loss (8% vs. 0%) in the topiramate group. Three patients in the 
amitriptyline group had serious adverse events of altered mood, and one patient 
in the topiramate group had a suicide attempt.
CONCLUSIONS: There were no significant differences in reduction in headache 
frequency or headache-related disability in childhood and adolescent migraine 
with amitriptyline, topiramate, or placebo over a period of 24 weeks. The active 
drugs were associated with higher rates of adverse events. (Funded by the 
National Institutes of Health; CHAMP ClinicalTrials.gov number, NCT01581281 ).