A quarter-century of montelukast: clinical lessons for adult and pediatric asthma and allergic rhinitis care

Montelukast entered routine respiratory practice in the late 1990s and remains widely used for asthma, allergic rhinitis (AR), and exercise-induced bronchoconstriction (EIBC). Its continued use has been driven largely by once-daily oral administration, ease of implementation, broad indications, and perceived advantages in patients with poor adherence to or difficulty using inhaled therapies. However, over time, the role of montelukast has evolved as comparative efficacy data, long-term safety findings, and treatment guidelines have modified expectations regarding its clinical value. This review re-examines the contemporary role of montelukast via integrating evidence on its mechanism of action, comparative clinical efficacy, prescribing patterns, safety outcomes, and future directions for individualized therapy. Clinical evidence demonstrates measurable benefit across asthma, AR, and EIBC; however, treatment effects are generally modest and variable and typically inferior to inhaled corticosteroid (ICS)-based regimens or intranasal corticosteroids (INCS). Nevertheless, patients, with poor inhaler adherence, exercise-related symptoms, aspirin-exacerbated respiratory disease, concomitant AR, or preference for oral therapy, may derive clinically meaningful benefit. Post-marketing surveillance has altered the therapeutic positioning of montelukast. Recognition of infrequent, but potentially serious, neuropsychiatric adverse events culminated in strengthened regulatory warnings and more cautious prescribing practices. Current management, therefore, emphasizes patient selection, pre-treatment counseling, shared decision-making, monitoring for behavioral changes, and timely review of treatment response. Current guidelines generally position montelukast as an alternative or add-on controller rather than a preferred first-line therapy. In the future, advances in pharmacogenomics, biomarker development, and phenotype-guided treatment strategies may improve the identification of patients most likely to benefit from montelukast.