Transcript Slide 1

JAMA Pediatrics Journal Club Slides:
Pharmacologic Treatment of Pediatric
Headaches
El-Chammas K, Keyes J, Thompson N, Vijayakumar J, Becher D,
Jackson JL. Pharmacologic treatment of pediatric headaches: a
meta-analysis. JAMA Pediatr. Published online January 28, 2013.
doi:10.1001/jamapediatrics.2013.508.
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Introduction
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Background
– Up to 15% of children and adolescents experience tension headaches;
4% experience migraines.
– Diagnostic criteria for migraines have evolved over time.
• Prior emphasis: tension vs migraine.
• Recent emphasis: acute vs chronic nature.
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– Diagnosis of headache in children and adolescents is especially
challenging because of the variety of symptoms, including abdominal
pain.
– Pharmacologic prophylaxis includes many options; decision regarding
agent typically depends on comorbid conditions and adverse effect
profile.
Study Objective
– To assist in clinical decision-making by conducting a meta-analysis to
assess comparative effectiveness and adverse effects of available
agents for prophylactic treatments.
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Methods
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Study Design
– Systematic review of randomized controlled trials identified through
PubMed, EMBASE, bibliographies of all retrieved articles, and Cochrane
Database of Clinical Trials for each class of medications.
– Evidence must have compared drug vs placebo OR 2 or more active
medications.
– Could be regarding tension, migraine, or chronic daily headache.
– Compared numbers of headaches across trials.
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Setting
– Multiple different trial settings across 21 studies.
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Patients
– Trials included adolescents (as young as 11 years) and adults.
– All but one trial focused on episodic migraine headaches.
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Methods
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Outcome
– Reduction in headaches with prophylaxis.
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Limitations
– Relatively small number of studies, focusing almost exclusively on
migraines.
– Use of different measures across studies.
– Heavy emphasis on a few medications (eg, propranolol) with relatively few
studies of other agents (eg, clonidine).
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Results
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Original search: 2918 articles.
Included in analysis: 21 randomized controlled trials.
– Common reasons for exclusion:
• Trial did not actually measure headaches (n = 221 trials).
• Review article (n = 102).
• Case series (n = 36).
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Distribution of medications most commonly tested (could include >1
medication in a given trial):
– Propranolol (n = 8).
– Flunarizine (n = 5).
– Topiramate (n = 3).
– Valproate (n = 3).
– Clonidine (n = 2).
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Results
Reduction in
headaches per
month among
placebocontrolled trials.
WMD indicates
weighted mean
difference.
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Results
Pooled Relative Risk of Adverse Effects Compared With Placebo
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Comment
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Limited evidence of efficacy of trazodone or topiramate for prophylaxis of
episodic migraines.
No evidence of efficacy beyond placebo for clonidine, flunarizine, pizotifen,
propranolol, or valproate.
Improvement with placebo was observed in several trials, with a mean
decrease of nearly 3 headaches per month.
Overall favorable adverse effects profile.
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Clinical trials in this arena are of markedly inconsistent quality and are often
too small to be certain of statistical differences when the clinical differences
appeared meaningful (eg, reduction of >2 headaches per month).
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There are very few trials on prophylaxis of headaches among children and
adolescents.
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Comment
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Adolescents could not be distinguished from adults through subgroup
analyses in these trials because there were too few children to permit robust
estimates.
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Comparative effectiveness assessment could not be performed because of
an insufficient number of subjects.
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Future research needs:
– Trials of children and adolescents with chronic daily headaches.
– Placebo controls in all trials, given strong placebo responses across
several trials.
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Contact Information
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If you have questions, please contact the corresponding author:
– Jeffrey L. Jackson, MD, MPH, Department of Medicine, Medical
College of Wisconsin, 5000 W National Ave, Milwaukee, WI
53295 ([email protected]).
Conflict of Interest Disclosures
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None reported.
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