Off-Label Use of Pharmacologic Interventions in Children with Headache

Educational Objectives

The goal of this program is to improve the management of headache in children and adolescents. After hearing and assimilating this program, the clinician will be better able to:

1. List pharmacologic interventions available for the treatment of headache in children.

2. Choose acute and preventive headache medications on the basis of their efficacy and side-effect profiles.

Summary

Principles of acute therapy: initiate treatment early, use high doses to combat gastroparesis, give patients choice of medication

Triptans: available in oral (PO), intranasal (IN) and injectable preparations; side effects and convenience important considerations; sumatriptan (Imitrex) — on market longest; PO doses of 25 mg, 50 mg, and 100 mg; start with 25 mg in smaller children; use 100 mg in teens; available in subcutaneous (SQ) formulations of 4 mg and 6 mg; use 4 mg SQ in younger patients; use up to 6 mg in teens, but may start with 4 mg due to possible side effects; IN formulation available in 5 mg, 10 mg, and 20 mg; multiple dosing options advantageous, but if not inhaled properly becomes oral preparation and tastes “terrible”; Treximet — combination of sumatriptan and naproxen, thus providing prostaglandin inhibition and release of 5-hydroxytryptamine (5-HT)

Reason use is off-label: many investigations have attempted to study migraine medications in pediatric patients; placebo response rate high in this age group; hidden coronary artery disease represents major worry with use of triptans, but extremely rare in children; safety high in most studies, but proof of efficacy lacking

Zolmitriptan: available in PO, melt (no need to swallow), and IN preparations; only 1 IN dose size, so not used in smaller children; 2 sizes of oral dose

Rizatriptan: available only in PO and melt doses

Naratriptan and frovatriptan: long-acting drugs; useful in menstrual migraine prophylaxis and combating bounce-back headache; speaker prescribes these (with steroids) after successful treatment of status migrainosus in ED

Dihydroergotamine (DHE, Migranal): IN form; advantage of flexible dosing; in adults, use 1 spray each nostril and repeat in 20 min (4 doses total); use 2 doses in older children, 1 dose in preschoolers

Treating status migrainosus: in ED or infusion center, DHE, metoclopramide, magnesium, steroids, valproate, and fluids may all be administered IV; combination involves no opioids, so discourages drug-seeking behavior; patients admitted if ED treatment fails; repeat DHE, steroids, valproate, and IV fluids until improvement seen

Principles of preventive drugs: criteria for need include absenteeism, presenteeism, and disability despite retraining in use of triptans; start with low dose and proceed slowly to avoid side effects; give patients realistic expectations of time required for improvement

Overview of preventive drugs: amitriptyline — start low, go slow; side effects include weight gain, difficulty waking, and dry mouth; cyproheptadine — start at 4 mg; side effects include difficulty waking and weight gain; gabapentin — can start as low as 300 mg (3600 mg maximum daily dose); usually well tolerated; compliance problematic, as dosing ideally 3 times daily; most clinicians prescribe twice-daily dosing; pregabalin (Lyrica) — can increase dose faster than with other preventive medicines; use if patient has fibromyalgia; topiramate (Topamax) — side effects include weight loss, eye pain or dryness, subtle learning problems, and word-finding difficulties; latter 2 reactions usually unacceptable for teenagers; propranolol — can cause foggy thinking, poor exercise tolerance, depression, and exacerbation of asthma; valproate — side effects include hair loss, foggy thinking, weight gain; levels must be checked; valproate plus topiramate good choice in patients with seizure disorder; has calming effect, so useful in conduct disorder; verapamil — causes constipation and dizziness; rarely used

Miscellaneous treatments: oral contraceptive pills used to eliminate menses in patients with menstrual migraine; acupuncture, dietary changes, and chiropractic; drugs are off-label in pediatric patients due to high placebo response rate, short duration of migraines, and failure to meet adult criteria in clinical trials

Summary: make right diagnosis; assess severity; decide by absenteeism and presenteeism whether preventive treatment warranted; define patient preferences; allow patient some choice in medications; identify comorbidities (depression, obesity, anxiety, sleep disturbance); establish partnership; use triptans early for acute treatment; be cautious when deciding who should receive preventive medicine

 

Readings

Derosier FJ et al: Randomized trial of sumatriptan and naproxen sodium combination in adolescent migraine. Pediatrics 2012; 129:1411-20. Dodick DW: Clinical practice. Chronic daily headache. N Engl J Med 2006; 354:158-65. Gladstein J, Mack KJ: Common presentations of chronic daily headache in adolescents. Pediatr Ann 2010; 39: 424-30. Gladstein J, Rothner AD: Chronic daily headache in children and adolescents. Semin Pediatr Neurol 2010; 17:88-92. Jacobs H, Gladstein J: Pediatric headache: a clinical review. Headache 2012; 52:333-9. Mack KJ, Gladstein J: Management of chronic daily headache in children and adolescents. Paediatr Drugs 2008; 10:23-9. Rothner AD: Complicated migraine and migraine variants. Curr Pain Headache Rep 2002; 6;233-9. Rothner AD et al: Zolmitriptan oral tablet in migraine treatment: high placebo responses in adolescents. Headache 2006; 46:101-9. Silberstein SD et al: Management of migraine: an algorithmic approach. Neurology 2000; 55:S46-52. Wang SJ et al: Chronic daily headache in adolescents: prevalence, impact and medication overuse. Neurology 2006; 66:193-7. Weidenfeld A, Borusiak P: Alice-in-Wonderland syndrome — a case-based update and long-term outcome in nine children. Childs Nerv Syst 2011; 27:893-6.