Donald W. Lewis

Practice Parameter: Pharmacological treatment of migraine headache in children and adolescents: Report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society

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.

Practice parameter: Evaluation of children and adolescents with recurrent headaches Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society

Objective The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence. For this parameter, the authors reviewed available evidence on the evaluation of the child with recurrent headaches and made recommendations based on this evidence. Methods Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification. Results There is inadequate documentation in the literature to support any recommendation as to the appropriateness of routine laboratory studies or performance of lumbar puncture. EEG is not recommended in the routine evaluation, as it is unlikely to define or determine an etiology or distinguish migraine from other types of headaches. In those children undergoing evaluation for recurrent headache found to have a paroxysmal EEG, the risk for future seizures is negligible; therefore, further investigation for epilepsy or treatments aimed at preventing future seizures is not indicated. Obtaining a neuroimaging study on a routine basis is not indicated in children with recurrent headaches and a normal neurologic examination. Neuroimaging should be considered in children with an abnormal neurologic examination or other physical findings that suggest CNS disease. Variables that predicted the presence of a space-occupying lesion included 1) headache of less than 1-month duration; 2) absence of family history of migraine; 3) abnormal neurologic findings on examination; 4) gait abnormalities; and 5) occurrence of seizures. ConclusionsRecurrent headaches occur commonly in children and are diagnosed on a clinical basis rather than by any testing. The routine use of any diagnostic studies is not indicated when the clinical history has no associated risk factors and the child’s examination is normal.

Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders

Objective: To test the hypothesis that atomoxetine does not significantly worsen tic severity relative to placebo in children and adolescents with attention deficit/hyperactivity disorder (ADHD) and comorbid tic disorders. Methods: Study subjects were 7 to 17 years old, met Diagnostic and Statistical Manual of Mental Disorders–IV criteria for ADHD, and had concurrent Tourette syndrome or chronic motor tic disorder. Patients were randomly assigned to double-blind treatment with placebo (n = 72) or atomoxetine (0.5 to 1.5 mg/kg/day, n = 76) for up to 18 weeks. Results: Atomoxetine treatment was associated with greater reduction of tic severity at endpoint relative to placebo, approaching significance on the Yale Global Tic Severity Scale total score (–5.5 ± 6.9 vs –3.0 ± 8.7, p = 0.063) and Tic Symptom Self-Report total score (–4.7 ± 6.5 vs –2.9 ± 5.2, p = 0.095) and achieving significance on the Clinical Global Impressions (CGI) tic/neurologic severity scale score (–0.7 ± 1.2 vs –0.1 ± 1.0, p = 0.002). Atomoxetine patients also showed greater improvement on the ADHD Rating Scale total score (–10.9 ± 10.9 vs –4.9 ± 10.3, p < 0.001) and CGI severity of ADHD/psychiatric symptoms scale score (–0.8 ± 1.1 vs –0.3 ± 1.0, p = 0.015). Discontinuation rates were not significantly different between treatment groups. Atomoxetine patients had greater increases in heart rate and decreases of body weight, and rates of treatment-emergent decreased appetite and nausea were higher. No other clinically relevant treatment differences were seen in any other vital sign, adverse event, or electrocardiographic or laboratory measures. Conclusions: Atomoxetine did not exacerbate tic symptoms. Rather, there was some evidence of reduction in tic severity with a significant reduction of attention deficit/hyperactivity disorder symptoms. Atomoxetine treatment appeared safe and well tolerated.

Children's Ibuprofen Suspension for the Acute Treatment of Pediatric Migraine

Objective.—To compare the efficacy of a single over‐the‐counter dose (7.5 mg/kg, p.o.) of childrens ibuprofen suspension vs. placebo for the acute treatment of pediatric migraine.

Rizatriptan 5 mg for the acute treatment of migraine in adolescents: A randomized, double-blind, placebo-controlled study

Objective.—To investigate the tolerability and efficacy of rizatriptan 5 mg in adolescent migraineurs.

Prophylactic Treatment of Pediatric Migraine

Background.—Migraine occurs in 3% to 5% of young children and up to 18% of adolescents. Management requires a tailored regimen of pharmacological and behavioral measures that consider the headache burden and disability. Patients with frequent or disabling attacks (or both) may warrant preventive agents.

Use of the ICHD-II criteria in the diagnosis of pediatric migraine

Objective.—To evaluate the sensitivity of the new International Classification of Headache Disorders‐2nd edition (ICHD‐II) criteria in the diagnosis of childhood migraine and to propose specific criteria for the diagnosis of childhood migraine.

Acute headache in children and adolescents presenting to the emergency department.

Objectives.–Our goals were (1) to investigate the causes of acute headache in childhood from the emergency department perspective and (2) to search for clinical clues that might distinguish headache associated with serious underlying disease.

The Utility of Neuroimaging in the Evaluation of Children With Migraine or Chronic Daily Headache Who Have Normal Neurological Examinations

Objectives.—To assess the utility of neuroimaging in the evaluation of children presenting with two of the most common forms of headache, migraine and chronic daily headache, and to determine the utility and pathological yield of neuroimaging in specific headache syndromes in children whose neurological examinations are normal.

Efficacy of zolmitriptan nasal spray in adolescent migraine.

OBJECTIVE. The goal was to evaluate the efficacy and tolerability of zolmitriptan nasal spray in the treatment of adolescent migraine. METHODS. The “Double-Diamond” study used a novel, single-blind, “placebo challenge” in a multicenter, randomized, double-blind, placebo-controlled, 2-way, 2-attack, crossover design. A total of 248 US adolescent patients (12–17 years of age) with an established diagnosis of migraine, with or without aura, were enrolled. A single-blind placebo challenge was used for each migraine attack. No additional medications were taken if a headache response to the initial placebo treatment was achieved at 15 minutes; if migraine intensity remained moderate or severe, then patients treated the attack with zolmitriptan (5 mg) nasal spray or placebo according to a randomized, crossover schedule (double-blind). The primary efficacy variable was headache response at 1 hour after treatment. A comprehensive range of secondary end points included sustained headache response at 2 hours. RESULTS. A total of 171 patients (mean age: 14.2 years; 57.3% female) treated ≥1 attack with study medication (intention-to-treat population). The onset of significant pain relief was apparent 15 minutes after treatment with zolmitriptan nasal spray. At 1 hour after the dose, zolmitriptan nasal spray produced a higher headache response rate than did placebo (58.1% vs 43.3%). Zolmitriptan nasal spray was also significantly superior to placebo in improvement in pain intensity, pain-free rates, sustained resolution of headache, and resolution of associated migraine symptoms. Return to normal activities was also consistently faster with zolmitriptan nasal spray than with placebo, with less use of any escape medication. Treatment with zolmitriptan nasal spray was well tolerated. CONCLUSIONS. This novel, placebo-challenge study demonstrated that zolmitriptan nasal spray was well tolerated and provided fast and significantly effective relief of migraine symptoms in the acute treatment of adolescent migraine.