Treatment of acute migraine attacks in children with analgesics on the World Health Organization Essential Medicines List: A systematic review

Article type
Authors
Jeric M1, Surjan N2, Jelicic Kadic A3, Riva N4, Moja L5, Puljak L2
1Department of Dermatovenerology, General Hospital Zadar, Zadar, Croatia
2Cochrane Croatia
3Department of Pediatrics, University Hospital Split, Split, Croatia
4Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
5Department of Essential Medicines and Health Products, World Health Organization, Geneva, Switzerland
Abstract
Background: The World Health Organization Essential Medicines List (WHO EML) contains two analgesics for treatment of acute migraine attacks in children: ibuprofen and paracetamol.

Objective: The aim of this study was to systematically analyse direct evidence from randomised-controlled trials (RCTs) and systematic reviews (SRs) about benefits and harms of these analgesics.

Methods: Embase, CDSR, CENTRAL, DARE and MEDLINE were searched. Two reviewers independently screened the literature and extracted data. Meta-analysis was conducted for pain-free at 2 h, pain relief at 2 h and adverse events. Studies were further analysed using Cochrane risk-of-bias tool, AMSTAR and GRADE methodology. The study was registered in PROSPERO.

Results: Three RCTs (including 201 children) and 9 SRs on ibuprofen or/and paracetamol for acute migraine attacks in children were included. The RCTs indicate that ibuprofen and paracetamol are more effective than placebo. The studies had few data about safety. The RCTs had unclear or high risk of bias on most of the domains. Meta-analysis of the trials indicated that ibuprofen was superior to placebo for number of children who were pain-free at 2 h or had pain relief at 2 h, but without difference in adverse events. There were no differences between paracetamol and placebo, neither between ibuprofen and paracetamol in those three outcomes. Quality of analysed outcomes was very low. The 9 SRs analysed various therapies for migraine in children, and were published between 2004 and 2016. Only two SRs included all three RCTs. Conclusions of SRs regarding efficacy of ibuprofen and paracetamol were discordant. The majority of the SRs were of low quality.

Conclusion: Limited data from RCTs indicate that ibuprofen is an effective analgesic for treating migraine attacks in children. Direct evidence for paracetamol is less conclusive. The available RCTs included small numbers of children and the trials were of poor quality. Inclusion of ibuprofen and paracetamol as anti-migraine medicines for children in the WHO EML is also based on indirect (i.e. studies in adults) and observational evidence (e.g. cohort studies).