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Original Investigation
February 10, 2020

Efficacy, Safety, and Acceptability of Pharmacologic Treatments for Pediatric Migraine Prophylaxis: A Systematic Review and Network Meta-analysis

Author Affiliations
  • 1School of Psychology, University of Plymouth, Plymouth, England
  • 2Division of Clinical Psychology and Psychotherapy, University of Basel, Basel, Switzerland
  • 3Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 4Institute of Medical Psychology, Medical Faculty, LMU Munich, Munich, Germany
  • 5IMBI Freiburg, Freiburg, Germany
  • 6School of Medicine, Institute of General Practice and Health Services Research, Technical University Munich, Munich, Germany
  • 7Division of Integrative Health Promotion, Coburg University of Applied Sciences, Coburg, Germany
JAMA Pediatr. 2020;174(4):341-349. doi:10.1001/jamapediatrics.2019.5856
Key Points

Question  What are the most effective, safe, and accepted pharmacologic treatments for migraine prophylaxis in children and adolescents?

Findings  In this network meta-analysis, comparing head-to-head and placebo-controlled trials found no significant long-term effects for migraine prophylaxis relative to placebo. Medium-sized short-term effects were found for propranolol and topiramate, but the prediction interval indicates that significant beneficial effects are to be expected in only 70% of similar studies conducted in the future.

Meaning  Considering the limited effect size, a cautious, individual, and tailored treatment approach to migraine prophylaxis is of great importance.


Importance  Migraine is one of the most common neurologic disorders in children and adolescents. However, a quantitative comparison of multiple preventive pharmacologic treatments in the pediatric population is lacking.

Objective  To examine whether prophylactic pharmacologic treatments are more effective than placebo and whether there are differences between drugs regarding efficacy, safety, and acceptability.

Data Sources  Systematic review and network meta-analysis of studies in MEDLINE, Cochrane, Embase, and PsycINFO published through July 2, 2018.

Study Selection  Randomized clinical trials of prophylactic pharmacologic treatments in children and adolescents diagnosed as having episodic migraine were included. Abstract, title, and full-text screening were conducted independently by 4 reviewers.

Data Extraction and Synthesis  Data extraction was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis network meta-analysis guidelines. Quality was assessed with the Cochrane Risk of Bias tool. Effect sizes, calculated as standardized mean differences for primary outcomes and risk ratios for discontinuation rates, were assessed in a random-effects model.

Main Outcomes and Measures  Primary outcomes were efficacy (ie, migraine frequency, number of migraine days, number of headache days, headache frequency, or headache index), safety (ie, treatment discontinuation owing to adverse events), and acceptability (ie, treatment discontinuation for any reason).

Results  Twenty-three studies (2217 patients) were eligible for inclusion. Prophylactic pharmacologic treatments included antiepileptics, antidepressants, calcium channel blockers, antihypertensive agents, and food supplements. In the short term (<5 months), propranolol (standard mean difference, 0.60; 95% CI, 0.03-1.17) and topiramate (standard mean difference, 0.59; 95% CI, 0.03-1.15) were significantly more effective than placebo. However, the 95% prediction intervals for these medications contained the null effect. No significant long-term effects for migraine prophylaxis relative to placebo were found for any intervention.

Conclusions and Relevance  Prophylactic pharmacologic treatments have little evidence supporting efficacy in pediatric migraine. Future research could (1) identify factors associated with individual responses to pharmacologic prophylaxis, (2) analyze fluctuations of migraine attack frequency over time and determine the most clinically relevant length of probable prophylactic treatment, and (3) identify nonpharmacologic targets for migraine prophylaxis.

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    1 Comment for this article
    Our time is the best prophylaxis to prevent migraine
    ALEJANDRO QUINONEZ, MD, PhD Physician | El Pilar Hospital, Guatemala City
    After 35 years of treating migraines I can say: nothing comes to be more succesfull than a comprhensive terapuetic plan for the patients; avoiding all the substances or habits that can be considered as a trigger for a new episode. The main issue remmains in takeing your time to speak with the patients and then help themselves to identify those risk factors involved in the process to prevent them. Trust me... they will really appreciate it.