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Psychiatric Disorders and Montelukast in Children: A Disproportionality Analysis of the VigiBase®

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Abstract

Introduction

In 2008, the US FDA issued an alert about an increased risk of psychiatric events associated with montelukast. Recent national pharmacovigilance analyses in Sweden, France and Spain detected a potential increase in reporting risk of the association.

Aim

Our objective was to analyse spontaneous reports of psychiatric events in children and adolescents worldwide treated with montelukast.

Methods

We conducted a retrospective analysis of Individual Case Safety Reports (ICSRs) recorded up to 1 January 2015 in the World Health Organization (WHO) database (VigiBase®), in which montelukast was associated with ‘psychiatric disorders’. We used the Bayesian Confidence Propagation Neural Network (BCPNN) approach for signal generation.

Results

A total of 14,670 ICSRs for montelukast were recorded, of which 2630 corresponded to psychiatric disorders in people aged <18 years. The main symptoms reported for infants (aged <2 years) were sleep disorders, for children (aged 2–11 years) the main symptoms were depression/anxiety, and for adolescents (aged 12–17 years) they were suicidal behaviour and depression/anxiety. Suicidal behaviour was over-represented in all age groups with information component (IC) values that reached 5.01 in children and 3.85 in adolescents. Unexpectedly, completed suicides were reported more frequently for children (IC: 3.15; IC025: 1.98) than for adolescents (IC: 3.11; IC025: 2.61) or the total population (IC 1.95; IC025: 1.73).

Conclusions

Neuropsychiatric disorders as side effects of montelukast were more frequently reported for children than for adults. Infants and children seem to be more prone to sleep disturbances, whereas adolescents present symptoms of depression/anxiety and psychotic reactions more often. Suicidal behaviour and completed suicide appear to be more frequently reported than previously thought in practice. Risk management plans and epidemiological studies are needed to quantify the risk. Practitioners should be aware of the risk of neuropsychiatric events associated with montelukast use, and should advise the patient and report new cases.

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Acknowledgments

Anders Viklund, from the WHO-UMC contributed to data retrieval and IC calculations from the WHO-UMC Database. Ralph Edwards, from the WHO-UMC, provided valuable comments on the analysis and interpretation of the data. The authors are indebted to the national centres that contributed data.

Author information

Authors and Affiliations

  1. Clinical Pharmacology Service, Hospital Universitario de Canarias, La Laguna, Spain

    Ana Aldea Perona & Mar García-Sáiz

  2. School of Health Sciences (Medicine), University of La Laguna, 38320, La Laguna, Spain

    Emilio Sanz Álvarez

Authors
  1. Ana Aldea Perona
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  2. Mar García-Sáiz
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  3. Emilio Sanz Álvarez
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Corresponding author

Correspondence to Emilio Sanz Álvarez.

Ethics declarations

This study is based on data mining and interpretation of the largest database for drug safety in the world (the WHO-UMC VigiBase®) and was conducted in accordance with their higher standards. Therefore, the CONSORT, PRISMA, EVEREST, STARD or STROBE statements could not be applied, nor could the study be registered in a ‘trial registration’ database. The study did not identify any individual patient and involved multinational data, so no Ethical Review Board approval was required.

Statements

This is an original study and has not been submitted to, or published by, in whole or part, any other journal.

The authors followed the WHO methodology for signal generation and the caveat document of the WHO collaborating Centre for International Drug Monitoring, the UMC (http://www.who-umc.org/DynPage.aspx?id=98082). Emilio Sanz Álvarez is a member of the WHO-UMC Signal Review Panel.

Funding

The study received no funding.

Conflicts of interest

Ana Aldea Perona, Mar García-Sáiz and Emilio Sanz Álvarez have no conflicts of interest that are directly relevant to the content of this work.

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Aldea Perona, A., García-Sáiz, M. & Sanz Álvarez, E. Psychiatric Disorders and Montelukast in Children: A Disproportionality Analysis of the VigiBase® . Drug Saf 39, 69–78 (2016). https://doi.org/10.1007/s40264-015-0360-2

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