Leukotriene Receptor Antagonists and Risk of Neuropsychiatric Entities: A Meta-Analysis of Observational Studies

Abstract

Background: Leukotriene receptor antagonists (LTRAs) are commonly prescribed to patients with allergic diseases. Several case reports and pharmacovigilance studies have indicated that LTRAs might increase the risk of neuropsychiatric (NP) entities. However, the results are mixed in observational studies. Thus, the association between LTRAs and NP entities remains controversial.

Objective: To quantitatively evaluate the NP risk with LTRAs based on current observational studies to provide a reference for clinical practice.

Methods: We systematically reviewed the literature in Medline, Embase, Web of Science, Cochrane Library, Scopus, and PsycINFO. A meta-analysis of observational studies that investigated the association between LTRA use and the risk of NP entities was performed. Odds ratios (OR) with 95% confidence intervals (CI) were used to measure the effect; heterogeneity was evaluated using I-squared (I²) statistics. Subgroup and sensitivity analyses were conducted to assess bias.

Results: Eleven articles were included in the primary analysis. No significant association was found between LTRA use and NP entities (OR: 1.08, 95% CI: 0.93-1.24, I² = 93.7%). In patients with allergic rhinitis (AR), a mildly increased NP risk was found (OR: 1.099, 95% CI: 1.004-1.202). The association between LTRA use and NP entities was not significant in patients with asthma (OR: 1.06, 95% CI: 0.90-1.26). LTRAs increased the risk of NP entities in a single study using data from an asthma clinic (OR: 9.00, 95% CI: 1.20-69.50), but not in studies from databases (OR: 1.07, 95% CI: 0.93-1.23).

Conclusion: At the population level, LTRAs and NP entities were unrelated. However, the association may exist in particular groups (eg, patients with AR or NP history). Subject-specific studies are required to further examine the relationship between LTRAs and NP entities and identify the underlying mechanisms.

Keywords: Leukotriene receptor antagonist; Meta-analysis; Neuropsychiatric entities.