Montelukast and Neuropsychiatric Outcomes in Asthma and Allergic Rhinitis

Girl blowing nose, allergic rhinitis, nasal congestion
Girl blowing nose, allergic rhinitis, nasal congestion
Are patients with asthma and allergic rhinitis who initiate montelukast at higher risk for sleep and anxiety disorders?

Patients with asthma and allergic rhinitis using montelukast — the most widely used leukotriene-modifying agent (LTMA) — had increased odds of experiencing neuropsychiatric outcomes after treatment initiation, according to study results recently published in JAMA Open Network.

Montelukast, a selective leukotriene receptor antagonist, is currently indicated for patients with asthma, allergic rhinitis, and exercise-induced bronchoconstriction, and is also sometimes used in patients with chronic obstructive pulmonary disease and obstructive sleep apnea. Although initial randomized controlled trials of montelukast showed mild and infrequent adverse effects, subsequent reports suggested possible association with aggression, anxiety, depression, sleep problems, and suicide, said researchers for the current study. The researchers therefore sought to examine the association between new montelukast exposure and 1-year incident neuropsychiatric diagnoses with the use of improved control and precision for baseline confounders.

The propensity score-matched cohort study used electronic health record (EHR) data captured between 2015 and 2019 in the TriNetX Analytics Network patient repository of more than 51 million patients, aged 15 to 64 years, from 56 health care organizations that were mostly located in the US (91% of patients were from the US; 9% from Europe). Researchers assessed 2 separate study populations — patients with asthma and patients with allergic rhinitis — with each group having a cohort of patients using montelukast and a control cohort of patients not using montelukast. A total of 475,869 patients who met eligibility criteria prior to matching were included, with 276,413 individuals in the asthma population and 199,456 individuals in the allergic rhinitis population.

Following propensity score matching for a variety of baseline confounders, which included dispensed prescription medications and comorbidities, 154,946 participants were included in the study. Of these, 77,473 had been exposed to montelukast. All participants were followed up for 12 months. The data obtained were analyzed between June 2021 and November 2021.

A total of 72,490 patients with asthma and 82,456 patients with allergic rhinitis were enrolled. Among the participants with asthma, 61.7% were women and the mean age at index prescription was 35±15 years. Among those with allergic rhinitis, 65.7% were women and the mean age at index prescription was 40±14 years.

The investigators found that participants in the montelukast-exposed asthma group had an increased likelihood of being diagnosed with an incident sleep disorder within 1 year of initial montelukast prescription, compared with those in the unexposed asthma group (odds ratio [OR], 1.13; 95% CI, 1.02-1.25). An association between montelukast and sleep disorders was seen with allergic rhinitis as well. Participants in the montelukast-exposed allergic rhinitis group had an increased likelihood of being diagnosed with an incident sleep disorder within 1 year of initial montelukast prescription, compared with those in the unexposed allergic rhinitis group (OR, 1.10; 95% CI, 1.01-1.20).

In both the asthma and the allergic rhinitis arms, montelukast exposure was associated with a 13% to 15% higher odds of receiving an incident diagnosis of insomnia within
12 months after the initial montelukast prescription, compared with those with no exposure (asthma: OR, 1.13; 95% CI, 1.01-1.27; allergic rhinitis: OR, 1.15; 95% CI, 1.05-1.27).

The researchers also found that individuals in the montelukast-exposed asthma group had higher odds of being diagnosed with any incident anxiety-related disorder within 1 year of initial montelukast prescription, compared with individuals who were not exposed to montelukast (OR, 1.21; 95% CI, 1.05-1.20).

Among participants who were exposed to montelukast, the ORs for any incident neuropsychiatric outcome were 1.11 (95% CI, 1.04-1.19) in those with asthma and 1.07 (95% CI, 1.01-1.14) in those with allergic rhinitis, compared with participants who were unexposed.

A major limitation of the current study is the fact that because the researchers used retrospective EHR data, they had no control over treatment allocation. Thus, the results of the study represent treatment decisions that were rendered in the clinic. Information on the duration of montelukast treatment or adherence was not available, which may have confounded any of the associations that were observed.

The investigators concluded that the findings from the present study show that “clinicians who prescribe montelukast and other LTMAs should discuss potential neuropsychiatric adverse events with patients before starting treatment and consider monitoring for signs of neuropsychiatric symptoms during treatment regardless of treatment indication.” This may be especially important in individuals with a history of mental health or sleep issues.

Disclosure: One of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures. 


Paljarvi T, Forton J, Luciano S, Herttua K, Fazel S. Analysis of neuropsychiatric diagnoses after montelukast initiation. JAMA Netw Open. 2022;5(5):e2213643. doi:10.1001/jamanetworkopen.2022.13643