Pediatric Migraine Trial Calls for Reevaluation of Approved Therapies

Joey Spada, Mercer University College of Pharmacy

Pediatric migraine has proven to negatively impact social abilities through missed school days and withdrawal from peer interactions. [1]  More than 6 million children and adolescents in the U.S. have migraines annually. [2]  Based on a survey of pediatric headache specialists, amitriptyline and topiramate are the two most commonly used preventive medications. [3]  Current guidelines recommend amitriptyline at a maximum dose of 1mg/kg and topiramate at 200 mg/day. [4]

Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine [5]
Design Randomized, double-blind, placebo-controlled; N= 361
Objective To compare amitriptyline, topiramate, and placebo for migraines in children and adolescents
Study Groups Amitriptyline (n= 144); topiramate (n= 145); placebo (n= 72)
Methods A baseline period of 28 days consisted of being monitored for headache (H/A) frequency and evaluation according to the Pediatric Migraine Disability Assessment Scale (PedMIDAS).  Patients who ranged in age from 8-17 years old were administered one capsule twice daily in divided doses.  Target doses were 1 mg/kg per day for amitriptyline and 2 mg/kg per day for topiramate.  Patients were treated for 24 weeks and scores were determined using PedMIDAS and compared to the results from the 28-day baseline period.  Values for PedMIDAS include: 0-10 = no disability; 11-30 = mild disability; 31-50 = moderate disability; >50 = severe disability.
Duration July 2012 – November 2014
Primary Outcome Measure Relative reduction of 50% or more in the number of H/A days and change in PedMIDAS scores
Baseline Characteristics   Amitriptyline Topiramate Placebo
Mean age, yrs ± SD 14.2 ± 2.4 14.2 ± 2.5 14.2 ± 2.2
Female, n (%) 97 (67) 101 (70) 49 (68)
Results   Amitriptyline Topiramate Placebo
≥ 50% relative reduction in H/A frequency, n (%) 69 (52) 72 (55) 40 (61)
p-value 0.26 0.48  N/A
PedMIDAS scores
Baseline 41.3 ± 27.9 41.2 ± 25.0 42.0 ± 27.0
Week 24 18.8 ± 25.3 14.4 ± 17.3 19.4 ± 20.8
p-value 0.91 0.13 N/A
H/A days per 28 day period
Baseline 11.3 ± 6.0 11.3 ± 5.7 11.1 ± 6.5
Week 24 4.6 ± 4.6 4.6 ± 5.3 5.2 ± 6.5
p-value 0.36 0.41  N/A
Adverse Events Common Adverse Events:

Amitriptyline: fatigue (30%), dry mouth (25%)

Topiramate: paresthesia (31%), fatigue (25%), memory impairment (17%), aphasia (16%), upper respiratory tract infection (12%), weight loss (8%)

Serious Adverse Events:

Amitriptyline: altered mood (2.1%), suicide attempt (0.7%), syncope (0.7%)

Topiramate: suicide (0.7%)

Percentage that Discontinued due to Adverse Events:

Amitriptyline (4.9%)

Topiramate (5.5%)

Study Author Conclusions There was no statistically significant difference in reduction of headache frequency or headache-related disability between amitriptyline, topiramate, or placebo.  Patients who received amitriptyline and topiramate had higher rates of adverse events compared to placebo.

During the course of this trial, the U.S. Food and Drug Administration approved topiramate for the treatment of episodic migraines in adolescents aged 12-17 years of age.  The trial included patients outside of this age range yet the results suggest that topiramate for migraine prevention may need to be reexamined.  Current consensus about the use of amitriptyline and topiramate in pediatric patients needs reevaluation as this study exposed lacking effectiveness considering placebo showed similar results for PedMIDAS scoring and headache frequency.



  1. Hershey AD. Current approaches to the diagnosis and management of pediatric migraine. Lancet Neurol. 2010;9(2):190-204.
  1. Stewart WF, Lipton RB, Celentano DD, Reed ML. Prevalence of migraine headache in the United States: relation to age, income, race, and other sociodemographic factors. JAMA. 1992;267:64-9.
  1. Hershey AD. Current approaches to the diagnosis and management of paediatric migraine. Lancet Neurol. 2010;9:190- 204.
  1. DiSabella M. Pediatric Headache: Consult and Referral Guidelines. Children’s National Medical Center. Available online at: _lecture_final.ashx?la=en. Accessed November 14th, 2016.
  1. Powers SW, Coffey CS, Chamberlin LA, et al. Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine. N Engl J Med. 2016.





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