Neuropsychiatric events associated with montelukast in patients with asthma: a systematic review

Abstract

Background:The United States Food and Drug Administration issued a black box warning on the mental health adverse effects of montelukast in 2020. Age-related effects on the risk of developing specific neuropsychiatric events in montelukast users remain largely unknown.Objective:To describe the risk of neuropsychiatric events associated with montelukast in adults and children with asthma.Methods:A systematic search of all studies investigating neuropsychiatric events in montelukast users was performed in PubMed, the Cochrane Library and Embase from inception to 7 September 2022. Animal studies and conference abstracts were excluded.Results:59 studies (21 pharmacovigilance studies, four reviews from 172 randomised controlled trials, 20 observational studies, 10 case reports and four case series) evaluating neuropsychiatric events in patients with asthma on montelukast were reviewed. No significant association was shown between montelukast and suicide-related events in six of the observational studies. No association was found for depression as defined by the International Classification of Diseases 10threvision codes in three observational studies and a review of randomised clinical trials. However, findings from four studies using antidepressant prescriptions as the outcome identified significant associations. Consistent with nine pharmacovigilance studies, two large-scale observational studies revealed possible associations of montelukast with anxiety and sleeping disorders in adult patients with asthma, respectively. However, the results were not replicated in two observational studies on children.Conclusion:Montelukast is not associated with suicide- and depression-related events in asthma patients. Older adults may be particularly susceptible to anxiety and sleeping disorders.

Promising Effects of Montelukast for Critically Ill Asthma Patients via a Reduction in Delirium

“…Ultimately, the results from our study demonstrated that pre-ICU exposure was greatly associated with the reduced incidence of delirium, suggesting a positive effect on the neuropsychiatric status of critically ill patients. However, it is important to note that MTK-related NAEs have been reported more frequently in children to date, possibly related to the fact that MTK is more commonly used in children, and possibly because children’s brains are at an early stage of maturation and the therapeutic effects of MTK are accompanied by a strong modulation of specific processes in the central system, resulting in a greater likelihood of adverse drug reactions [ 26 ]. Unfortunately, the MIMIC-IV database used in this study did not include data on ICU patients under 18 years of age, and only patients with a median age of 66 years were included, limiting the generalizability of the findings to the pediatric population.…”

Much ado about montelukast: A side‐effects saga

“…Moreover, in a Danish nationwide health registry study of adults, montelukast was associated with increased neuropsychiatric events, albeit only in younger age groups (Jordan et al, 2023). And yet, a meta‐analysis of all studies examining neuropsychiatric events with montelukast found no association with suicide‐ and depression‐related events (Lo et al, 2023).…”