Is there a relation between montelukast (Singulair) and suicidal ideation, and what is the approach to managing this risk in patients with respiratory conditions?

Montelukast and Suicide Risk: Clinical Approach

Yes, there is a documented association between montelukast and neuropsychiatric adverse events including suicidal ideation, though the evidence regarding actual suicide risk remains conflicting, and the FDA has issued a boxed warning for these risks. 1

Established Neuropsychiatric Risks

The FDA drug label explicitly warns that neuropsychiatric events have been reported in patients taking montelukast, including 1:

• Suicidal thinking and behavior (including suicide)
• Agitation and aggressive behavior or hostility
• Depression
• Anxiousness
• Dream abnormalities and hallucinations
• Insomnia and sleep disturbances
• Irritability and restlessness

Patients and prescribers must be alert for these neuropsychiatric events, and prescribers should carefully evaluate the risks and benefits of continuing treatment if such events occur. 1

Evidence Quality and Contradictions

Supporting Evidence for Association:

• Post-marketing surveillance data from the FDA Adverse Event Reporting System showed significantly elevated reporting odds ratios: 21.5 for suicidal ideation and 8.2 for depression 2
• Global pharmacovigilance analysis identified 2,630 psychiatric disorder reports in children, with suicidal behavior over-represented across all age groups 3
• Functional gene analysis suggests montelukast interacts with pathways involved in "neuroactive ligand-receptor interaction" and "mood disorders" 2

Contradictory Evidence:

• The most recent and highest quality observational study from Sweden (2025) involving 74,291 children found no association between montelukast use and neuropsychiatric adverse events compared to long-acting β-agonists (HR 0.99,95% CI 0.84-1.16) 4
• A systematic review of 59 studies found no significant association between montelukast and suicide-related events in six observational studies 5
• Merck's adjudicated review of 22,433 patients in clinical trials identified only 1 suicidal ideation event in 9,929 montelukast patients versus none in controls 6

However, the European Respiratory Society acknowledges that evidence of the association is conflicting. 7

Age-Specific Patterns

The risk profile varies by age group 3:

• Infants (<2 years): Predominantly sleep disorders
• Children (2-11 years): Depression/anxiety and unexpectedly high rates of completed suicide reports (IC: 3.15)
• Adolescents (12-17 years): Suicidal behavior, depression/anxiety, and psychotic reactions
• Older adults: May be particularly susceptible to anxiety and sleeping disorders 5

Clinical Approach in Australia

When to Prescribe Montelukast:

The European Respiratory Society provides clear guidance 7:

• Do NOT use montelukast as first-line therapy for chronic rhinosinusitis or asthma
• Consider only when patients do not tolerate nasal corticosteroids
• Do NOT add montelukast to intranasal corticosteroids (no additional benefit demonstrated) 7
• The American Academy of Family Physicians indicates montelukast is primarily for asthma as alternative therapy for mild persistent asthma 8

Mandatory Patient Counseling:

Before prescribing, patients must be instructed to 1:

1. Immediately notify their prescriber if neuropsychiatric changes occur
2. Understand that montelukast is NOT for acute asthma attacks
3. Keep short-acting bronchodilator rescue medication available
4. Continue taking daily even when asymptomatic
5. Not discontinue other asthma medications without physician instruction

Monitoring Protocol:

• Screen for pre-existing psychiatric conditions before initiating therapy (patients with major depressive disorder, anxiety disorder, or history of psychosis are at highest risk) 7
• Active surveillance for mood changes, sleep disturbances, behavioral changes, or suicidal thoughts at each follow-up
• Lower threshold for discontinuation in children and adolescents given the disproportionate reporting in these age groups 3
• Consider alternative therapies (inhaled corticosteroids, long-acting bronchodilators) which have superior efficacy profiles without these risks 8

When to Discontinue Immediately:

Stop montelukast if the patient develops 1:

• Any suicidal thinking or behavior
• New or worsening depression or anxiety
• Agitation or aggressive behavior
• Hallucinations or psychotic symptoms
• Significant sleep disturbances or dream abnormalities

Critical Clinical Caveat

The 2025 Swedish study provides the most robust evidence suggesting no increased risk, but this contradicts FDA warnings based on post-marketing surveillance. 4 Given that neuropsychiatric events can have catastrophic consequences (suicide), and that montelukast offers limited therapeutic advantage over safer alternatives like inhaled corticosteroids, the prudent approach is to avoid montelukast unless absolutely necessary and to maintain heightened vigilance when it is prescribed. 7, 8, 1

The European Respiratory Society's position is clear: montelukast should not be routinely prescribed due to lack of supporting evidence and these safety concerns. 8