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Neuropsychiatric Events Associated with Leukotriene-Modifying Agents: A Systematic Review

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Abstract

Introduction

Leukotriene-modifying agents (LTMAs) including montelukast, zafirlukast, and zileuton are approved by the US Food and Drug Administration (FDA) for the treatment of asthma and allergic rhinitis. Various neuropsychiatric events (NEs) have been reported; however, the evidence of the association is conflicting. This systematic review investigates the association between NEs and LTMAs by assessing the relevant published literature.

Methods

PubMed, EMBASE, MEDLINE, and Cochrane Library were searched using keywords. Studies designed to investigate the association were eligible for inclusion without restriction to any study design or language. The primary outcome was defined as suicidal conditions, while secondary outcomes included all other NEs.

Results

Thirty-three studies were included for a narrative review. Four observational studies did not find a significant association, while ten pharmacovigilance studies using different global databases detected the signals. Notably, some studies suggest that the FDA warning issued in 2008 might have influenced the reporting rate of NEs as a result of increased awareness.

Limitations

The risk of NEs was not quantified, because of the lack of randomized controlled trials and observational studies investigating the association.

Conclusion

Many pharmacovigilance studies have been conducted to determine the association between NEs and LTMAs, but there is limited evidence from observational studies. High-quality epidemiological studies should be conducted to evaluate the association and quantify the risk, not only in children, but also in adults.

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Acknowledgements

We thank Joseph E. Blais (Centre for Safe Medication Practice and Research) for proofreading the manuscript.

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Authors and Affiliations

  1. Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Office 02-08, 2/F Laboratory Block, 21 Sassoon Road, Hong Kong SAR, China

    Sharon W. Y. Law, Angel Y. S. Wong, Shweta Anand, Ian C. K. Wong & Esther W. Chan

  2. Research Department of Practice and Policy, School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK

    Ian C. K. Wong

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  1. Sharon W. Y. Law
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Corresponding author

Correspondence to Esther W. Chan.

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Funding

The study was partially supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKU 789813).

Conflict of interest

Sharon W.Y. Law, Angel Y.S. Wong, Shweta Anand, Ian C.K. Wong, and Esther W. Chan declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Law, S.W.Y., Wong, A.Y.S., Anand, S. et al. Neuropsychiatric Events Associated with Leukotriene-Modifying Agents: A Systematic Review. Drug Saf 41, 253–265 (2018). https://doi.org/10.1007/s40264-017-0607-1

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