Treating migraines: It’s different for kids
Certain medications used for migraine prevention in adults do not perform the same way in children and adolescents and can actually cause harm.
PRACTICE CHANGER
Do not prescribe amitriptyline or topiramate as preventive therapy for migraine in children; both drugs are no better than placebo for this population and are associated with increased rates of adverse events.1,2
STRENGTH OF RECOMMENDATION
A: Based on a single double-blind randomized control trial (RCT) and supported by a meta-analysis of 4 RCTs.
1. Powers SW, Coffey CS, Chamberlin LA, et al; for the CHAMP Investigators. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017;376:115-124.
2. Le K, Yu D, Wang J, et al. Is topiramate effective for migraine prevention in patients less than 18 years of age? A meta-analysis of randomized controlled trials. J Headache Pain. 2017;18:69.
STUDY SUMMARY
Both drugs are no better than placebo in children
A multicenter, double-blind RCT by Powers and colleagues compared the effectiveness of amitriptyline, topiramate, and placebo in the prevention of pediatric migraines.1 Target dosing for amitriptyline and topiramate was set at 1 mg/kg/d and 2 mg/kg/d, respectively. Titration toward these doses occurred over an 8-week period based on reported adverse effects. Patients then continued their maximum tolerated dose for an additional 16 weeks.
Patients were predominantly white (70%), female (68%), and 8 to 17 years of age. They had at least 4 headache days over a prospective 28-day pre-treatment period and a Pediatric Migraine Disability Assessment Scale (PedMIDAS) score of 11 to 139 (mild to moderate disability=11-50; severe disability >50).1,8 The primary endpoint consisted of at least a 50% relative reduction (RR) in the number of headache days over the 28-day pre-therapy (baseline) period compared with the final 28 days of the trial.1
The authors of the study included 328 patients in the primary efficacy analysis and randomly assigned them in a 2:2:1 ratio to receive either amitriptyline (132 patients), topiramate (130 patients), or placebo (66 patients), respectively. After 24 weeks of therapy, there was no significant difference between the amitriptyline, topiramate, and placebo groups in the primary endpoint (52% amitriptyline, 55% topiramate, 61% placebo; adjusted odds ratio [OR]=0.71; 98% CI, 0.34-1.48; P=.26 between amitriptyline and placebo; OR=0.81; 98% CI, 0.39-1.68; P=.48 between topiramate and placebo; OR=0.88; 98% CI, 0.49-1.59; P=.49 between amitriptyline and topiramate).
There was also no difference in the secondary outcomes of absolute reduction in headache days and headache-related disability as determined by PedMIDAS. The study was stopped early for futility. Compared with placebo, amitriptyline significantly increased fatigue (number needed to harm [NNH]=8) and dry mouth (NNH=9) and was associated with 3 serious adverse events of altered mood. Compared with placebo, topiramate significantly increased paresthesia (NNH=4) and weight loss (NNH=13) and was associated with one serious adverse event—a suicide attempt.1
