D2.146 - Neuropsychiatric events associated with montelukast in children: a systematic review

Montelukast is widely prescribed in children for the treatment of asthma and allergic rhinitis. In recent years, concerns have been raised regarding potential neuropsychiatric adverse effects. The existing literature provides inconsistent findings, and the overall risk of these adverse events in children remains unclear. The aim of this study was to systematically evaluate the association between montelukast use and neuropsychiatric adverse events in the pediatric population and to synthesize available evidence through meta-analysis.

A systematic review of the literature was conducted by searching PubMed, Cochrane Library, Embase, and Scopus databases. Studies evaluating neuropsychiatric adverse events associated with montelukast use in children and adolescents (<20 years) were eligible for inclusion. A meta-analysis was performed using RevMan 5.4 software to assess risk of any neuropsychiatric events and specifically mood disorders, anxiety, attention-deficit/hyperactivity disorder (ADHD), psychotic symptoms, and suicide and/or suicidal attempts.

A total of 65 studies were included: 25 pharmacovigilance studies, 18 cohort studies, 14 case reports, 5 case–control studies and 3 randomized controlled trials. Into meta-analysis 6 studies were included with different number of studies contributing to individual outcomes. The meta-analysis demonstrated no statistically significant association between montelukast use and the analyzed neuropsychiatric outcomes. However, different studies, especially pharmacovigilance studies, showed association of montelukast with different neuropsychiatric adverse events, especially  mood changes, anxiety, sleep disturbances, behavioral problems, psychotic symptoms, and suicidal ideation. 

The results of this systematic review and meta-analysis do not indicate a clear increase in the risk of neuropsychiatric adverse events associated with montelukast use in children. However, given the heterogeneity of the available evidence and limitations of the included studies, a potential risk cannot be definitively excluded. Clinicians should remain attentive to neuropsychiatric symptoms when prescribing montelukast in pediatric patients. Further high-quality prospective studies are warranted to better clarify causality and define the neuropsychiatric safety profile of montelukast in children.