Exploring the possible association between montelukast and neuropsychiatric events among children with asthma: a matched nested case-control study

Abstract

Purpose: There is conflicting evidence regarding the association between montelukast and neuropsychiatric events (NE). We sought to examine this association among children with asthma.

Methods: Using a 10% sample of the LifeLink Health Plan Claims data, subjects less than 18 years of age with a primary diagnosis of asthma between 1 January 1998 and 31 December 2009 were identified. A range of case definitions for NE was formulated based on diagnoses of psychiatric disorders and use of psychotropic medications. Using a matched nested case-control design, three controls were matched to each case on age, gender and geographic region, and assigned a matching index date. Exposure to montelukast was measured as any exposure during the year, recency of exposure, cumulative duration of exposure, and cumulative dose. Conditional logistic regression was used to estimate unadjusted and adjusted odds ratio (OR) controlling for potential confounders.

Results: Using the broadest case definition, 1920 cases were identified. Subjects exposed to montelukast during the prior year had an unadjusted OR of 1.09 (95%CI [0.96, 1.22]) and adjusted OR of 1.01 (95%CI [0.88, 1.14]) for experiencing NE measured using the broadest definition. A clear dose-response relationship was not observed. Exposure to a moderate chronic cumulative dose of montelukast (481 mg-1050 mg) had a higher odds of being diagnosed with neuropsychiatric disturbances (OR = 1.27; 95%CI [1.03, 1.57]) while exposure to high cumulative doses (>1050 mg) had a lower odds (OR = 0.64; 95%CI [0.50, 0.82]).

Conclusions: These data did not detect a consistent significant positive association between montelukast and NE in children with asthma.

Keywords: montelukast; neuropsychiatric events; pharmacoepidemiology; psychiatric adverse events; psychiatric disorders; psychotropic medications.