Iatrogenic harm in paediatric and adolescent populations of patients with migraine: A systematic review with meta-analysis

Background: Migraine is a common condition that causes a high burden of disability even at a young age, significantly affecting various aspects of quality of life. Despite this significant burden, the pharmacological treatment of migraine is still a subject of debate, with controversial results that do not provide sufficient evidence of its effectiveness. Furthermore, the safety profile in this inherently fragile population leaves some doubts about pharmacological prophylaxis use. This study aims to provide an overview of the safety profile of the main drugs used in populations of children and adolescents with migraine, analysing the type and frequency of the main side effects reported. Methods: PubMed and Scopus were systematically searched for papers reporting adverse events (AEs) of pharmacological prophylaxis of migraine in children and adolescents, and all eligible original articles were included. A meta-analysis was carried out to define the pooled proportion of the summary safety information (i.e. the number of subjects reporting at least one AE) with 95% confidence intervals for those compounds present in at least two samples, regardless of dosage. Results: In total, 40 studies were included, accounting for 62 subsamples and 2742 patients (55% females). The most used compounds were topiramate (22 subsamples), propranolol and sodium valproate (six subsamples). Overall, 30% of patients reported at least one AE. Erenumab showed the highest rate of AEs, most likely due to the higher-precision detection typical of a randomized controlled trial, and cinnarizine the lowest. In total, 53 different AEs were reported, most frequently drowsiness, anorexia, fatigue and paraesthesia. Conclusions: In accordance with the results of this systematic review with a meta-analysis, clinicians should consider that 30% of the paediatric patients with migraine will report some AEs from prevention treatment. The information on the safety profile is essential for clinicians in evaluating the choice of a specific therapy, making a better risk/benefit ratio evaluation for each single patient, which is crucial in consideration of the inconsistent efficacy profiles of preventive medications, with the exception of topiramate, in this population.