Efficacy comparison of combined montelukast-antihistamine and montelukast monotherapy in allergic rhinitis: a meta-analysis of randomized controlled trials

Kim JS, Stybayeva G, Hwang SH.  Eur Ann Allergy Clin Immunol. 2025 Oct 31. doi: 10.23822/EurAnnACI.1764-1489.420. 

SUMMARY

Background. Combination therapy with montelukast and oral antihistamines is commonly used in allergic rhinitis (AR), but its comparative benefit over montelukast monotherapy remains unclear. This meta-analysis aimed to evaluate the efficacy of combination therapy compared to monotherapy, with a focus on symptom-specific outcomes. 

Methods. A comprehensive search of PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases was conducted through April 2025. We systematically reviewed randomized controlled trials comparing montelukast combined with oral antihistamines to montelukast monotherapy in patients with AR. Outcomes included total symptom scores, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores, and individual symptom domains. Pooled effects were analyzed using standardized mean differences (SMDs) with 95% confidence intervals (CIs). 

Direct comparison of changes in total symptom scores and
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)
scores between combination therapy and
montelukast monotherapy.

Results. Thirteen RCTs enrolling 2,950 patients were identified. Combination therapy significantly improved daytime symptoms (SMD = 0.25; 95%CI 0.15 to 0.35), with limited benefit for nighttime symptoms (SMD = 0.10; 95%CI -0.01 to 0.21) or RQLQ scores (SMD = 0.11; 95%CI -0.05 to 0.26). In subgroup analysis, all combinations with loratadine, desloratadine, or levocetirizine showed greater efficacy than monotherapy in improving daytime symptoms.

However, only the levocetirizine-based combination demonstrated a significant benefit for nighttime symptoms. When analyzed by individual symptoms, the levocetirizine combination resulted in significantly better outcomes than monotherapy, improving sneezing, nasal itching, nasal obstruction, and rhinorrhea. 

Conclusions. Montelukast combined with antihistamines improves daytime and individual nasal symptoms more effectively than monotherapy. However, the effectiveness of each drug combination varied by symptom domain. These findings may assist clinicians in selecting appropriate combination regimens based on individual symptom patterns.

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