Montelukast Effects on the Brain
Montelukast has been associated with various neuropsychiatric events, though the evidence of this association is conflicting, with recent large-scale studies showing no significant increased risk in children and adolescents. 1, 2, 3
Neuropsychiatric Effects
The FDA has included a boxed warning for montelukast (Singulair) regarding potential neuropsychiatric events, which should be carefully considered when prescribing this medication 2
Reported neuropsychiatric adverse events associated with montelukast include:
- Agitation and aggressive behavior/hostility
- Anxiety and depression
- Dream abnormalities and sleep disorders
- Hallucinations and irritability
- Suicidal thinking and behavior
- Tremor and restlessness 2
These neuropsychiatric events have been documented in post-marketing surveillance across different age groups, though with varying frequencies and presentations 1, 4
Age-Related Differences in Neuropsychiatric Effects
Different age groups appear to experience different types of neuropsychiatric symptoms:
A 2023 systematic review found that montelukast is not significantly associated with suicide-related events or depression in patients with asthma, though older adults may be particularly susceptible to anxiety and sleeping disorders 4
Recent Evidence on Safety
A large 2025 nationwide cohort study from Sweden (n=74,291 children) found no association between montelukast use and neuropsychiatric adverse events when compared to long-acting β-agonists in children and adolescents aged 6-17 years 3
This study showed no significant differences in:
- Overall neuropsychiatric events (HR 0.99,95% CI 0.84-1.16)
- Anxiety (HR 0.79,95% CI 0.54-1.14)
- Depression (HR 1.16,95% CI 0.70-1.95)
- Sleep-related disorders (HR 0.93,95% CI 0.76-1.13)
- Suicide and suicidal actions (HR 1.31,95% CI 0.64-2.69) 3
However, a 2025 cohort study from multiple Pediatric Allergy and Immunology centers found an increase in caregiver-reported neuropsychiatric symptoms in children from 14.8% to 34.3% after one month of montelukast treatment 6
Potential Mechanisms
A 2021 study analyzing drug-gene interaction networks suggested that montelukast interacts with genes enriched in "neuroactive ligand-receptor interaction" pathways and genes associated with mood disorders and major depressive disorder 7
The exact mechanism by which montelukast might cause neuropsychiatric effects remains incompletely understood, but may involve interactions with multiple neurological pathways 7
Clinical Recommendations
Patients and prescribers should be alert for neuropsychiatric events when using montelukast 2
Patients should be instructed to notify their prescriber if neuropsychiatric changes occur 2
Prescribers should carefully evaluate the risks and benefits of continuing treatment with montelukast if neuropsychiatric events occur 2
Montelukast is not recommended as first-line therapy for conditions where other treatments with better established safety profiles are available 8
The European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) does not recommend montelukast for chronic rhinosinusitis unless in situations where patients do not tolerate nasal corticosteroids 1
Monitoring and Management
When prescribing montelukast, inform patients and caregivers about potential neuropsychiatric side effects 2
Consider baseline assessment of mood, behavior, and sleep patterns before initiating therapy 6
Monitor patients regularly for emergence of neuropsychiatric symptoms, particularly during the first weeks of treatment 6
If significant neuropsychiatric symptoms develop, consider discontinuing montelukast and switching to alternative therapies 2
The risk-benefit assessment should be individualized, taking into account the severity of the condition being treated and the availability of alternative therapies 1, 8