While all patients using montelukast for asthma had higher risk for neuropsychiatric prescriptions, those aged 18 to 45 had higher risk for neuropsychiatric diagnoses.
Montelukast use in adults with asthma is significantly associated with increased risk for neuropsychiatric events, especially among younger adults aged 18 to 44 years, according to study findings published in The Journal of Allergy and Clinical Immunology: In Practice.
Studies suggest that use of montelukast, a selective leukotriene receptor antagonist frequently used to treat asthma and allergy, may result in adverse neuropsychiatric effects. Investigators in Denmark therefore assessed the association between montelukast use in adults with asthma and the onset of neuropsychiatric adverse events. Study outcomes were: (1) use of neuropsychiatric medicine (anxiolytics, antipsychotics, antidepressants, lithium and medication used for attention deficit/hyperactivity disorder), and (2) hospital contacts (ie, admissions or outpatient visits) within 90 days of montelukast use involving a neuropsychiatric diagnosis.
The investigators conducted a retrospective cohort study of adult patients with asthma using data from several Danish nationwide health registers with information on prescription drugs and hospitalizations. The study included 2 patient cohorts, 1 for each of the study’s main outcomes. Cohort 1, which evaluated use of neuropsychiatric medicine among patients with asthma, excluded patients who had filled prescriptions for neuropsychiatric medicine during the 6 months prior to their inclusion in the study; cohort 2, which identified patients with asthma who had hospital contacts with a neuropsychiatric diagnosis within 90 days of treatment, excluded patients with hospital or outpatient visits related to a neuropsychiatric disorder within 6 months prior to their inclusion in the study. Patients were followed for outcomes from the date of their inclusion in the databases (sometime between January 2011 and December 2018) through December 31, 2020.
Overall, more than 180,000 patients were included in the study, the majority of whom were 18 to 44 years of age. Patients exposed to montelukast in follow-up were more likely to use long-acting muscarinic antagonist and long acting β2-agonist at baseline vs patients not exposed to montelukast and more likely to have experienced asthma exacerbations.
In cohort 1, which assessed the use of neuropsychiatric medicine, median follow-up time was 2736 days, and the median time using montelukast was 310 days (interquartile range [IQR], 188-881). Among the 157,000 patients assessed for this outcome, 37,268 (24%) had redeemed at least 1 neuropsychiatric drug prescription during the observation period. Investigators found montelukast significantly associated with use of neuropsychiatric medicines (hazard ratio [HR], 1.14; 95% CI, 1.08-1.20; P <.0001).
In cohort 2, which assessed hospital contacts with a neuropsychiatric diagnosis, median follow-up time was 2761 days, and the median time using montelukast was 323 days (IQR, 188-911). Among the 180,000 patients assessed for this outcome, 15,596 (9%) had at least 1 hospital contact during the observation period with a neuropsychiatric diagnosis. The investigators found that risk of neuropsychiatric diagnosis was significantly associated with montelukast use only in the younger age groups studied (age group 18-29 years; HR, 1.28; 95% CI, 1.12-1.47; P <.001; age group 30-44 years; HR, 1.16; 95% CI, 1.02-1.31; P <.05).
Risk of both outcomes increased with decreasing age. The highest risk was seen in patients 18 to 29 years of age, in age-stratified analyses. The researchers found no association between the outcomes studied and montelukast use among patients 45 years of age or older. Investigators further noted that patients with prior neuropsychiatric disorders who used montelukast were not at significantly greater risk of adverse neuropsychiatric outcomes.
Significant study limitations include inability to detect patients who discontinued montelukast due to neuropsychiatric side effects without medical treatment or physician contact and lack of information on patients treated at psychology clinics or only at general practitioner offices without subsequent prescription or hospital referral.
“Among younger individuals, montelukast use was significantly associated with an increased risk of neuropsychiatric events such as use of neuropsychiatric medicine and hospital treatment,” investigators concluded.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Jordan A, Toennesen LL, Eklof J, et al. Psychiatric adverse effects of montelukast – a nationwide cohort study. J Allergy Clin Immunol Pract. Published online March 20, 2023. doi:10.1016/j.jaip.2023.03.010