Clinical Question

Is topiramate (Topamax) or amitriptyline effective for prophylaxis of migraine in children?

Bottom Line

Topiramate, amitriptyline, and placebo all led to a similar, substantial improvement in migraine frequency and disability. How to harness this strong placebo effect for our patients is an important, but unanswered, question. (Level of Evidence = 1b)

Synopsis

Migraine is a relatively common problem in children, but until recently there were no U.S. Food and Drug Administration–approved drugs for migraine prophylaxis in children (topiramate was approved in 2014). The most commonly used drugs are amitriptyline and topiramate. However, these drugs had not been studied in a clinical trial. In this study, the researchers enrolled 361 children (eight to 17 years of age) with chronic migraine, at least mild disability, and at least four headache days in a 28-day period. Their mean age was 14 years, 68% were female, and 70% were white. Their mean migraine disability score was 41.4, consistent with moderate severity, and they had a mean of 11 headaches during the 28-day baseline period. Groups were balanced at the start of the study. Participants were randomized in a 2:2:1 ratio to amitriptyline (in a target dosage of 1 mg per kg per day), topiramate (2 mg per kg per day), or placebo (twice per day). The trial was ended early because of futility, leading to some patients contributing only a portion of their headache diary data to the results. The mean migraine disability score decreased (from 41.4) to 19 in the amitriptyline group, 14 in the topiramate group, and 19 in the placebo group. Headache frequency declined similarly in all three groups from a mean of 11 to five. Adverse effects were much more common in the active treatment groups, including dry mouth and fatigue. There was a single suicide attempt in the topiramate group, and none in the other groups.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Setting: Outpatient (specialty)

Reference: Powers SW, Coffey CS, Chamberlin LA, et al.; CHAMP Investigators. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017;376(2):115-124.