Treating Migraine in Teenagers

Amitriptyline has consistently shown efficacy in adult migraine trials and is therefore one of the most commonly used medications worldwide for prevention of migraine in children and adolescents. Surprisingly, there have been no published randomized controlled trials using amitriptyline in the pediatric population, although a trial comparing amitriptyline, topiramate, and placebo is currently underway (Childhood and Adolescent Migraine Prevention Study) [43].In 2 retrospective pediatric studies improvement with amitriptyline was reported in 84.2% and 89% of patients, respectively [44,45].We typically use a goal dose of 1 mg/kg/day, also with an 8- to 12-week titration. The most common side effects with amitriptyline are somnolence, dry mouth, and weight gain, but it is generally well tolerated in children and adolescents. There is also a risk of worsening depression and suicidal thoughts, so it is recommended to use caution if considering prescribing to a patient with underlying depression. It is typically administered in once daily dosing a few hours before bed to minimize morning drowsiness. There is also a concern for precipitation of arrhythmias, and while there are no guidelines recommending screening ECGs, this should be considered in patients with a family history of heart disease. Of note, many practitioners use nortriptyline in place of amitriptyline as it can be less sedating. It should be noted, however, that evidence for its efficacy is lacking. Additionally, it may carry a higher risk of arrhythmia [44].

Second-line Therapies

The second-line therapies typically considered are other antiepileptics, valproic acid, levetiracetam, and zonisamide, for which there is some evidence, although mostly in the form of open-label or retrospective studies [46–51]. Of note, despite the many promising retrospective and open-label studies for valproic acid [46–48], one randomized double-blind placebo control trial comparing various doses of extended release divalproex sodium with placebo in adolescent patients failed to show a statistically significant treatment difference between any dose and placebo [52].It is, however, frequently prescribed and anecdotally quite efficacious. Given concerns about potential for teratogenicity, and possible effects on ovarian function, as well as potential for weight gain and hair loss, it should be used with caution in adolescent females.

Antihypertensives (beta blockers and calcium channel blockers) have long been used for prevention of migraine in both the adult and pediatric population, but evidence for their use in the pediatric population is conflicting. An early double-blind crossover study of propranolol in patients 7 to 16 years old showed significant efficacy as compared with placebo [53].However, in 2 subsequent studies it failed to show efficacy as compared with placebo and self-hypnosis, respectively [54,55].Given the conflicting evidence and the potential for hypotension, depression, and exercise-induced asthma, use of propranolol has fallen out of favor by experts for use in pediatric and adolescent migraine prevention. Flunarizine, a nonselective calcium channel blocker, has demonstrated effectiveness in pediatric migraine prevention [56,57],and is actually approved in Europe for this indication, but it is not available in the United States.

Cyproheptadine is an antihistamine with antiserotonergic properties which is used frequently for migraine prevention in young children who are unable to swallow tablets, although evidence is limited to 1 retrospective study [45].However, given the propensity for weight gain with this medication, it is generally not recommended for use in adolescents.