Evaluating montelukast-second-generation antihistamine combinations versus monotherapy in allergic rhinitis: A network meta-analysis

Background: Allergic rhinitis (AR) is an atopic condition affecting over 400 million people worldwide, impairing quality of life and often leading to complications such as asthma and sinusitis. Montelukast, a leukotriene receptor antagonist, is often used in combination with second-generation antihistamines (sgAHs) to enhance symptom control. However, the relative efficacy of different montelukast-sgAH combinations remains unclear. Objective: To evaluate and compare the efficacy of montelukast combined with various sgAHs versus montelukast monotherapy in patients with AR. Methods: Randomized controlled trials (RCTs) comparing montelukast-sgAH combinations to montelukast alone were identified from 5 electronic databases up to 2025. Outcomes included Total Nasal Symptom Score (TNSS; 0–12), Daytime and Nighttime Nasal Symptom Scores (DNSS, NNSS; 0–3), and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ; 0–6). Risk of bias (RoB) was assessed using Cochrane RoB 2.0. A frequentist network meta-analysis with subgroup analysis and meta-regression was performed using RStudio and Jeffreys’s Amazing Statistics Program. Results: Seventeen RCTs involving 2,655 participants were included. For TNSS improvement, montelukast + desloratadine combination is significantly better than monotherapy in adults (mean difference [MD] = −0.92 [−1.15 to −0.69]) and children (MD = −1.95 [−3.46 to −0.44]). Effects on RQLQ and DNSS were inconsistent, while NNSS improved with montelukast-levocetirizine ( P = 0.0384). Heterogeneity was high, but most studies showed low risk of bias. No serious adverse events were reported. Conclusion: Montelukast-sgAH combinations may improve symptoms over monotherapy, especially with desloratadine in both adults and children. However, variability across outcomes and high heterogeneity warrant cautious interpretation and further research.