Symptomatic treatment of migraine in children: a systematic review of medication trials.
OBJECTIVE
Treatment of pediatric migraine includes an individually tailored regimen of both nonpharmacologic and pharmacologic measures. The mainstay of symptomatic treatment in children with migraine is intermittent oral or suppository analgesics, but there is no coherent body of evidence on symptomatic treatment of childhood migraine available. The objective of this review is to describe and assess the evidence from randomized and clinical controlled trials concerning the efficacy and tolerability of symptomatic treatment of migraine in children.


METHODS
Systematic review according to the standards of the Cochrane Collaboration.


METHODS
Databases were searched from inception to June 2004. Additional reference checking was performed. Two authors independently selected randomized and controlled trials evaluating the effects of symptomatic treatment in children (<18 years old) with migraine, using headache (HA) clinical improvement as an outcome measure. Two authors assessed trial quality independently by using the Delphi list, and data were extracted from the original reports by using standardized forms. Quantitative and qualitative analysis was conducted according to type of intervention.


RESULTS
A total of 10 trials were included in this review, of which 6 studies were considered to be of high quality. The number of included participants in each trial ranged from 14 to 653, with a total of 1575 patients included in this review. Mean dropout rate was 19.8% (range: 0-39.1%), and the mean age of participants was 11.7 +/- 2.2 years (range: 4-18 years). All studies used HA diaries to assess outcomes. In most studies, a measure of clinical improvement was calculated by using these diaries. Improvement often was regarded as being clinically relevant when the patients' HA declined by > or =50%. Regarding oral analgesic treatment, the effectiveness of acetaminophen, ibuprofen, and nimesulide were evaluated. When compared with placebo, acetaminophen (relative risk [RR]: 1.5; 95% confidence interval [CI]: 1.0-2.1) and ibuprofen (pooled RR: 1.5; 95% CI: 1.2-1.9) significantly reduced HAs. We conclude that there is moderate evidence that both acetaminophen and ibuprofen are more effective in reduction of symptoms 1 and 2 hours after intake than placebo with minor adverse effects. No clear differences in effect were found between acetaminophen and ibuprofen or nimesulide. Regarding the nonanalgesic interventions, nasal-spray sumatriptan, oral sumatriptan, oral rizatriptan, oral dihydroergotamine, intravenous prochlorperazine, and ketorolac were evaluated. When compared with placebo, nasal-spray sumatriptan (pooled RR: 1.4; 95% CI: 1.2-1.7) seemed to significantly reduce HAs. We conclude that there is moderate evidence that nasal-spray sumatriptan is more effective in reduction of symptoms than placebo but with significantly more adverse events. No differences in effect were found between oral triptans and placebo. All medications were well tolerated, but significantly more adverse events were reported for nasal-spray sumatriptan compared with placebo. We also conclude that there is moderate evidence that intravenous prochlorperazine is more effective than intravenous ketorolac in the reduction of symptoms 1 hour after intake. No differences in effect were found between oral dihydroergotamine and placebo.


CONCLUSIONS
Acetaminophen, ibuprofen, and nasal-spray sumatriptan are all effective symptomatic pharmacologic treatments for episodes of migraine in children. The new frontier for symptomatic treatment is likely to be the development of triptan agents for use in children. Most treatments have only been evaluated in 1 or 2 studies, which limits the generalizability of the findings. We strongly recommend performing a large, high-quality randomized, controlled trial evaluating different symptomatic medications compared with each other or to placebo treatment. Favorable high-quality studies should be performed and reported according to the CONSORT statement. Clinical improvement of HA should be used as the primary outcome measure, but quality of life, days missed at school, and satisfaction of child or parents should also be used as an outcome measure in future studies.
Damen
Léonie
L
Department of General Practice, Erasmus Medical Centre, PO Box 1738, 3000 DR, Rotterdam, The Netherlands.
Bruijn
Jacques K J
JK
Verhagen
Arianne P
AP
Berger
Marjolein Y
MY
Passchier
Jan
J
Koes
Bart W
BW
D000082:Acetaminophen / Q000627:therapeutic use; D000293:Adolescent; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D018849:Controlled Clinical Trials as Topic; D004087:Dihydroergotamine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use; D020910:Ketorolac / Q000627:therapeutic use; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy*; D011346:Prochlorperazine / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D018170:Sumatriptan / Q000627:therapeutic use
D018712:Analgesics, Non-Narcotic; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D000082:Acetaminophen; D004087:Dihydroergotamine; D018170:Sumatriptan; C012655:nimesulide; D007052:Ibuprofen; D011346:Prochlorperazine; D020910:Ketorolac