Last reviewed: 19 Dec 2020
Last updated: 25 Aug 2020
25 Aug 2020

US FDA strengthens warning of risk of serious neuropsychiatric events associated with montelukast, and advises restricting use for allergic rhinitis

The US Food and Drug Administration (FDA) has strengthened its warnings for montelukast (a leukotriene receptor antagonist) with regard to the risk of serious behaviour- and mood-related changes. The FDA has taken this action after re-evaluating the risks and benefits of montelukast following a review of submitted case reports and published observational and animal studies, and carrying out an observational study of FDA safety data.

For allergic rhinitis, the FDA has determined that montelukast should be reserved for those who are not treated effectively with, or cannot tolerate, other allergy medicines.

Warnings about the risk of neuropsychiatric events (including suicidal thoughts or actions) are already included in the prescribing information for montelukast, but many healthcare professionals and patients/carers are not aware of the risk.

Montelukast is indicated for the relief of symptoms of allergic rhinitis; the prevention and chronic treatment of asthma; and the acute prevention of exercise-induced bronchoconstriction.

See Management: approach

See Management: treatment algorithm

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History and exam

Key diagnostic factors

  • presence of risk factors
  • sneezing
  • nasal pruritus

Other diagnostic factors

  • palate, throat, ear, and eye itching
  • eye redness, puffiness, and watery discharge
  • fatigue and irritability
  • nasal congestion
  • rhinorrhoea
  • allergic shiners
  • conjunctival injection
  • ocular mucoid discharge
  • nasal crease
  • pale nasal mucosa
  • swelling of the nasal mucosa and turbinates
  • abundant clear nasal secretions
  • Dennie-Morgan lines (creases present under the lower eyelids)

Risk factors

  • family history of atopy
  • age <20 years
  • positive allergen skin-prick tests
  • inadequate exposure to animals and other micro-organism-rich environments in early life
  • Western lifestyle
  • ethnicity
  • environmental pollution
  • exposure to indoor allergens such as animal dander and dust mites
  • heavy maternal smoking (20 or more cigarettes/day during the first year of life)
  • early introduction of foods or formula
  • breastfeeding
  • presence of other atopic conditions (eczema, food allergies, wheezing/asthma)

Diagnostic investigations

1st investigations to order

  • therapeutic trial of antihistamine or intranasal corticosteroid
More 1st investigations to order

Investigations to consider

  • allergen skin-prick testing
  • in vitro specific IgE determination
More investigations to consider

Treatment algorithm



American College of Allergy, Asthma & Immunology

Medical Director

American Academy of Allergy, Asthma & Immunology Registry

Assistant Clinical Professor of Medicine

Medical College of Wisconsin

Adjunct Clinical Instructor

College of Nursing

University of Wisconsin-Milwaukee

Executive Director

Fight Asthma Milwaukee Allies

Allergy, Asthma & Sinus Center




GCS has taken part in sponsored research for the ALK clinical trial of the house dust mite SLIT tablet for use in paediatric patients. He is a member of the Joint Task Force on Practice Parameters Workgroup on the Allergic Rhinitis Practice Parameter.

Dr Gary C. Steven would like to gratefully acknowledge Dr Alexander Greiner, a previous contributor to this topic.


AG has received grant/research support from: Astra Zeneca; Boehringer Ingelheim; Cephalon Circassia Ltd; Clement Clarke Cytos biotechnology; GlaxoSmithKline; Glenmark Specialty, S.A.; Hoffman-LaRoche/Genentech; HRA/Novartis; Janssen Research & Development; Kalypsys , Inc.; Lupin; Merck; Mylan Pharmaceuticals, Inc.; Nestle (Nestec Ltd); Novartis Ono Pharmaceutical Co., Ltd.; Perrigo; Rigel Pharmaceuticals, Inc.; Roxane Laboratories Inc.; Shionogi Inc.; Sunovion TEVA Branded Pharmaceutical Products; UBC (United Biosource Corporation)/Amgen Pharmaceuticals; and sponsorship for pharmaceutical trials from Allergen Research Corporation/Aimmune Therapeutics, Inc. and Astra Zeneca.

Peer reviewersVIEW ALL

Clinical Immunology Coordinator

Division of Rheumatology, Immunology and Allergy

Winthrop-University Hospital




MDL declares that he has no competing interests.

Consultant Allergist/Rhinologist

Allergy & Rhinology Department

Royal National Throat, Nose and Ear Hospital




GS is a consultant/advisory board member for ALK, Britannia Pharmaceuticals, CMP Therapeutics, Groupo Uriach, GSK, Merck, Sanofi-Aventis, Schering Plough, and UCB. She has received research funds from ALK, GSK, UCB, and Schering Plough. She has given talks for ALK, GSK, Merck, Schering Plough, and UCB and has co-written articles for Schering Plough and GSK.

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