Amitriptyline and Topiramate Are No More Effective Than Placebo for Pediatric Migraine

November 28, 2016

Amitriptyline and Topiramate Are No More Effective Than Placebo for Pediatric Migraine

  1. Cara Adler, MS

Neither drug was better than placebo at preventing headaches in this randomized trial, and both drugs were associated with higher rates of some adverse events.

  1. Cara Adler, MS

Although amitriptyline and topiramate are commonly used to treat pediatric migraine, there is no FDA-approved treatment for children younger than 12. Researchers at 31 U.S. sites randomized 361 children aged 8 to 17 years with migraine to amitriptyline (1 mg/kg per day), topiramate (2 mg/kg per day), or placebo for 24 weeks. The trial was stopped early for futility.

Patients kept a symptom diary for 28 days before randomization and for the last 28 days of the trial. The primary outcome was a 50% or greater relative reduction in the number of headache days between the two periods. Analyses were adjusted for age (8–12 vs. 13–17) and headache frequency during the baseline period (episodic, 4–14 vs. chronic, ≥15).

Rates of the primary outcome were similar in the amitriptyline, topiramate, and placebo groups (52%, 55%, and 61%). There were also no significant differences between groups in change in headache-related disability (measured with the PedMIDAS score), change in number of headache days, percentage of patients who completed treatment, and incidence of serious adverse events. However, some adverse events were significantly more frequent in the active-treatment groups compared with controls, including paresthesia and weight loss in the topiramate group and fatigue and dry mouth in the amitriptyline group. There was one suicide attempt in the topiramate group.

Comment — Pediatrics and Adolescent Medicine

  1. Louis M. Bell, MD

It is interesting that although amitriptyline and topiramate prevented migraines in adult studies, they were not effective in this well-designed pediatric study. As primary care pediatricians, we are left with stressing the nonmedication fundamentals for prevention of migraine, including adequate fluid intake, avoiding caffeine, adequate sleep (at least 8 hours a day), eating three meals a day, exercise, using a headache diary to identify triggers, and finding time for relaxation (music, play, yoga). Discussing migraine prevention with our pediatric neurology colleagues in light of these findings will be important. In the meantime, I would consider holding off on giving prophylactic therapy because the adverse effects appear to outweigh the benefits.

Comment — Neurology

  1. Amy Gelfand, MD

The CHAMP study set out to identify optimal first-line migraine preventive therapy for the typical child or adolescent with migraine who presents to care. The equal effectiveness of amitriptyline, topiramate, and placebo treatments seen in approximately 60% of the subjects tells us several things:

1) A multidisciplinary approach that includes regular education about healthy habits is likely helpful.

2) Providing optimally dosed, evidence-based acute migraine therapy (specifically nonsteroidal anti-inflammatory drugs and triptans), along with clear instruction on how often to use them, is likely helpful.

3) Expectation of benefit from a migraine preventive is likely important in driving subsequent improvement.

Because a reduction in headache days did not occur during the 4-week baseline period before study medication was initiated, despite provision of a multidisciplinary approach that included excellent headache education and acute medications, these interventions alone should not be considered adequate preventive treatment. As all three arms of the study were effective, we should not withhold migraine preventive therapy from children who need it. Such therapy may include a supplement that has a suggestion of being active for migraine prevention (e.g., CoQ10, riboflavin, magnesium, melatonin) and avoids the more challenging side-effect profile of prescription agents. These supplements should be thought of as medications and treated as such. Cognitive-behavioral therapy is also an evidence-based part of the preventive treatment plan for 10- to17-year-olds with chronic migraine (JAMA 2013; 310:2622). Future research should focus on how best to treat the approximately 40% of pediatric migraine patients who do not improve with first-line therapy and children and adolescents who have continuous headache, concurrent medication overuse, or both, as these patients were not studied in CHAMP.

Dr. Gelfand is Assistant Professor, Department of Neurology, Division of Child Neurology, University of California, San Francisco.

Editor Disclosures at Time of Publication

  • Disclosures for Louis M. Bell, MD at time of publication Grant / Research support NIH Institutional Clinical and Translational Science Award; Agency for Healthcare Research and Quality National Center for Pediatric Practice Based Research Learning; Patient-Centered Outcomes Research Institute Editorial boards Current Problems in Pediatric Adolescent Healthcare (Associate Editor)


Reader Comments (2)

Debra Chesman, MSW Other, Mother of migraine suffering child

In our experience and the anecdotal stories of other families, sometimes, the migraine as it is diagnosed by neurology and pediatrics, may actually be the migraine-like headache of Lyme Disease. Doctors need to learn that an initial test for Lyme, not coming out fully "CDC positive", does not necessarily rule out Lyme Disease. Riddle: What can fool 6 neurologists, 3 pediatricians, but not a mother who suffers migraine herself? Lyme Disease in a child which was allowed to become chronic for 3 years, untreated. Six years later, the child still has a Lyme headache and can't finish school thanks to doctors refusing to learn about Lyme and refusing to keep it in the differential diagnosis. Instead, they were quick to suggest antidepressants and couseling and blame the child for her headaches, when the non-local Lyme species and 2 co-infections were to blame. And this was after the child's real migraine history included unhelpful amitriptyline, topiramate and a so-called migraine diet, not to mention antidepressants that had to be cafefully withdrawn agaist the advice of the neurologists, who didn't know that they made a child into bed-wetter and suicidal. They also didn't listen to us that Topomax caused bad mood (perhaps from blood sugar drops?) in an adolescent, but blamed the parenting skills of not understanding a teen! Neurology has a long way to go before they should be allowed to treat children.

MR M L OHARE Other, Other, United Kingdom

Magnesium Malate
Vity B12
Vit B2
L trypt

3grm Melatonin at bedtime

4 years single blind tests. This works

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