Drug interventions for acute treatment of pediatric migraine: a systematic review and network meta-analysis

Migraine in children and adolescents not only impacts academic pursuits and family life but also have secondary psychological effects. Determining the role of acute medication for migraine treatment in this population can reduce the burden associated with migraine. This network meta-analysis aimed to identify the relative efficacy and safety of acute migraine drug in children and adolescents migraine populations.

The Cochrane Register of Controlled Trials and MEDLINE via PubMed and Embase databases were searched from inception to August 2025, only published studies in English. Double-blind randomized clinical trials evaluating the currently available acute treatments for childhood and adolescent migraines were included. The primary efficacy endpoint was pain freedom at 2 hours. Secondary efficacy endpoints included the proportion of participants with pain relief at 2 hours, pain freedom from two to 24 h, and the proportion using rescue drugs after 2 hours and up to 24 h. Adverse events (AEs) were also evaluated.

The analysis included 30 studies (involving 8,914 participants and 13 pharmacological interventions). All treatments included demonstrated higher odds ratios (ORs) compared with the placebo for pain freedom at 2 hours. Dihydroergotamine was associated with the highest ORs, but its confidence interval included null values. Sumatriptan/naproxen sodium, ibuprofen, zolmitriptan nasal spray, sumatriptan nasal spray, and rizatriptan showed statistical significance. Sumatriptan/naproxen sodium yielded the highest odds (OR: 2.91, 95% CI: 1.87-4.53), followed by ibuprofen (OR: 2.88, 95% CI: 1.47-5.64), and rizatriptan showed the lowest (OR: 1.51, 95% CI: 1.23-1.86). Only sumatriptan/naproxen sodium was associated with a significantly higher OR compared with placebo for pain freedom from two to 24 h (OR: 2.31, 95% CI: 1.31-4.07). Ibuprofen exhibited the highest effect size for pain relief at 2 hours (OR: 3.21, 95% CI: 1.10-9.34). None of the included drugs was found to reduce the use of rescue drugs from two to 24 h. Zolmitriptan was associated with the highest risk of AEs among all treatments. Acetaminophen appears to have the lowest risk of adverse events, comparable to that of a placebo.

Ibuprofen can effectively relieve symptoms, characterized by a favorable benefit-risk profile. Sumatriptan and zolmitriptan nasal sprays also exhibited robust efficacy, specifically among populations with prominent nausea and vomiting. Sumatriptan/naproxen sodium merits consideration, especially in patients exhibiting an inadequate response to monotherapy. Dihydroergotamine demonstrated potential benefits in refractory and chronic migraine; however, high-quality studies are warranted to validate these findings.