Practice Parameter: Pharmacological treatment of migraine headache in children and adolescents

Objective: To review evidence on the pharmacologic treatment of the child with migraine headache. Methods: The authors reviewed, abstracted, and classified relevant literature. Recommendations were based on a four-tiered scheme of evidence classification. Treatment options were separated into medications for acute headache and preventive medications. Results: The authors identified and reviewed 166 articles. For acute treatment, five agents were reviewed. Sumatriptan nasal spray and ibuprofen are effective and are well tolerated vs placebo. Acetaminophen is probably effective and is well tolerated vs placebo. Rizatriptan and zolmitriptan were safe and well tolerated but were not superior to placebo. For preventive therapy, 12 agents were evaluated. Flunarizine is probably effective. The data concerning cyproheptadine, amitriptyline, divalproex sodium, topiramate, and levetiracetam were insufficient. Conflicting data were found concerning propranolol and trazodone. Pizotifen, nimodipine, and clonidine did not show efficacy. Conclusions: For children ( age 6 years), ibuprofen is effective and acetaminophen is probably effective and either can be considered for the acute treatment of migraine. For adolescents ( 12 years of age), sumatriptan nasal spray is effective and should be considered for the acute treatment of migraine. For preventive therapy, flunarizine is probably effective and can be considered, but is not available in the United States. There are conflicting or insufficient data to make any other recommendations for the preventive therapy of migraine in children and adolescents. For a clinical problem so prevalent in children and adolescents, there is a disappointing lack of evidence from controlled, randomized, and masked trials. NEUROLOGY 2004;63:2215–2224 Migraine headaches are common in children and occur with increasing frequency through adolescence.1-6 The reported prevalence increases from 3% (age 3 to 7 years) to 4 to 11% (age 7 to 11) to 8 to 23% (age 11 to 15 ) with the mean age at onset being 7.2 years for boys and 10.9 years for girls.7,8 The evaluation of a child with recurrent headaches begins with a thorough medical and family history followed by a complete physical examination with measurement of vital signs, particularly blood pressure, and complete neurologic examination including examination of the optic fundi. Recently, a Endorsed by the American Academy of Pediatrics and the American Headache Society. Approved by the QSS on April 27, 2004; by the Practice Committee on August 7, 2004; and by the AAN Board of Directors on October 16, 2004. From the Division of Child Neurology (Dr. Lewis), Department of Pediatrics, Children’s Hospital of the King’s Daughters, Eastern Virginia Medical School, Norfolk; Division of Child Neurology (Dr. Ashwal), Department of Pediatrics, Loma Linda University School of Medicine, CA; Department of Neurology (Dr. Hershey), Children’s Hospital Medical Center, Cincinnati, OH; National Institute of Neurological Disorders and Stroke (Dr. Hirtz), NIH, Bethesda, MD; Division of Child Neurology (Dr. Yonker), Department of Pediatrics, AI Dupont Hospital for Children, Wilmington, DE; and Jefferson Headache Center (Dr. Silberstein), Jefferson University, Philadelphia, PA. D.L. has grant funded research grants from Astra-Zeneca, Ortho-McNeil, Merck, American Home Products, GlaxoSmithKline, Abbott Laboratories, and Eli Lilly. A.H. has grant support from MedPointe, Pfizer, and Ortho-McNeil; advisory board for Astra-Zeneca and Ortho-McNeil; grant support from GlaxoSmithKline, Ortho-McNeil, and UCB Pharma; pharmaceutical studies sponsored by AstraZeneca, GSK, Ortho-McNeil, Johnson & Johnson, and Abbott Laboratories. M.Y. has grant funded research from Ortho-McNeal and Astra-Zeneca. S.S. is on the advisory panel, speakers bureau, or serves as a consultant for Abbott, Allergan, AstraZeneca, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Merck, Metis, NPS, Pfizer, Pozen, UCB Pharma, and X-Cel Pharmaceuticals; he receives research support from Abbott, Allergan, AstraZeneca, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Medtronics, Merck, NPS, Pfizer, Pozen, UCB Pharma, and X-Cel Pharmaceuticals. Received May 11, 2004. Accepted in final form September 8, 2004. Address correspondence and reprint requests to American Academy of Neurology, 1080 Montreal Avenue, St. Paul, MN 55116. Copyright © 2004 by AAN Enterprises, Inc. 2215 practice parameter that outlined guidelines for the clinical and laboratory evaluation of children and adolescents with recurrent headaches was published.9 Diagnosis of primary headache disorders of children rests principally on clinical criteria as set forth by the International Headache Society (IHS, 1988).10 In 2004, the IHS published a modified International Classification of Headache Disorders (ICHD) for primary (e.g., including migraine, with and without aura) and secondary headache disorders (table 1).11 For young children, the 1988 IHS criteria were too restrictive, and the second edition ICHD criteria have incorporated more developmentally sensitive criteria.12-16 Consensus-based criteria for pediatric migraine are essential for the conduct of future clinical treatment trials. Appropriate treatment for children and adolescents with migraine requires an individually tailored strategy giving due consideration to both pharmacologic and nonpharmacologic measures in the context of the degree of disability produced by the headache. Not all children require pharmacologic intervention. Treatment of migraine headaches in children has remained difficult for both parents and physicians. In young children, accurate diagnosis, assessment of the severity of symptoms, and recognition of associated symptoms is complicated by the inability of children to articulate their complaints. In addition, other infectious, allergic, or gastrointestinal disorders of childhood may mimic symptoms of migraine. Therefore, medications directed specifically for the treatment of childhood migraine may be of limited value if there are other conditions present that mimic or even precipitate migraine. Of equal importance has been the difficulty in using medications either acutely or for preventive purposes in children and adolescents that have shown efficacy in adults, as the appropriate safety and efficacy studies have not been conducted. This practice parameter reviews the evidence on the pharmacologic treatment of migraine in children and adolescents. Nonpharmacologic treatments and biobehavioral measures are not addressed. Description of process. Three organizations participated in the development of this practice parameter, including the American Academy of Neurology (AAN), the Child Neurology Society, and the American Headache Society. The American Academy of Pediatrics reviewed the manuscript. Computer-assisted literature searches were conducted with the help of the AAN and the University of Minnesota Biomedical Information Services Research Librarian for relevant articles published from 1980 through December 2003. Databases searched included Medline and Current