Montelukast Safety Concerns
Montelukast carries an FDA black box warning for serious neuropsychiatric events including suicidal thoughts and behavior, and should not be used for mild disease when safer alternatives like intranasal corticosteroids are available. 1
Primary Safety Concern: Neuropsychiatric Events
The FDA issued a black box warning in 2020 specifically highlighting the following risks 1:
- Suicidal thoughts and actions
- Depression and anxiety
- Sleep disturbances and dream abnormalities
- Behavioral changes including agitation and aggressive behavior 2
- Hallucinations and psychotic symptoms 3
Evidence Quality and Magnitude of Risk
While some evidence is conflicting 4, 3, recent large-scale analysis of 154,946 patients found statistically significant increased odds of neuropsychiatric outcomes 5:
- Anxiety disorders: 21% increased odds in asthma patients 5
- Insomnia: 15% increased odds in allergic rhinitis patients 5
- Pediatric analyses show particularly concerning signals for suicidal behavior, with unexpectedly high reporting of completed suicides in children 6
When NOT to Prescribe Montelukast
Do not prescribe montelukast in these situations 1:
- Mild disease adequately controlled with intranasal corticosteroids
- Allergic rhinitis as first-line therapy (intranasal steroids are more effective) 1, 3
- Chronic rhinosinusitis unless patient cannot tolerate nasal corticosteroids 4, 3
The FDA explicitly states that benefits may not outweigh risks when disease is mild and treatable with alternatives 1.
Pre-Prescribing Requirements
Before initiating montelukast 3:
- Screen for pre-existing psychiatric conditions (depression, anxiety, suicidal ideation history)
- Explicitly discuss neuropsychiatric risks including suicidal thoughts with patient/family 1
- Document that safer alternatives were considered or are inappropriate
Monitoring Protocol
Monitor particularly closely during the first weeks of therapy 1:
- Active surveillance for mood changes at each follow-up 3
- Sleep disturbances or dream abnormalities 3
- Behavioral changes (agitation, aggression, restlessness) 2
- Suicidal thoughts at every visit 3
Instruct patients to immediately notify prescriber if any neuropsychiatric changes occur 3, 2.
Immediate Discontinuation Criteria
Stop montelukast immediately if patient develops 3:
- Suicidal thinking or behavior
- New or worsening depression or anxiety
- Agitation or aggressive behavior
- Hallucinations or psychotic symptoms
- Significant sleep disturbances or dream abnormalities
Do not continue therapy without reassessing risk-benefit even if symptoms are mild 1.
Other Notable Adverse Effects
Beyond neuropsychiatric concerns 1:
- Headache (common)
- Hepatitis and elevated liver enzymes (less common but important)
- Eosinophilia (rare but serious, possible association with Churg-Strauss syndrome)
- Pancreatitis (reported but causality not established) 1
Critical Clinical Pitfalls
Common prescribing errors to avoid 1, 3:
- Using as first-line for conditions where intranasal steroids are appropriate
- Failing to discuss neuropsychiatric risks before prescribing
- Not monitoring for behavioral changes in follow-up visits
- Continuing therapy after emergence of any neuropsychiatric symptoms
- Prescribing for acute asthma attacks (not indicated) 2
Special Considerations
- Not for acute bronchospasm or status asthmaticus 2
- Cannot be abruptly substituted for inhaled or oral corticosteroids 2
- Pregnancy Category B - may be used when there has been uniquely favorable prepregnancy response 1
- Phenylketonuric patients: chewable tablets contain phenylalanine 2
- Neuropsychiatric effects can occur years after initiation, not just at start of therapy 7