Montelukast and Suicide Risk: Clinical Guidance
Montelukast carries a significant risk of neuropsychiatric events including suicidal thoughts and behaviors, warranting careful consideration before prescribing and close monitoring during treatment. The FDA has issued a black box warning specifically highlighting these risks, indicating that the benefits of montelukast may not outweigh the risks, especially when symptoms are mild and can be adequately treated with other medications 1.
Evidence of Neuropsychiatric Effects
The FDA's black box warning for montelukast (Singulair) was established based on post-marketing reports that documented serious neuropsychiatric events including:
- Suicidal thinking and behavior (including completed suicide)
- Depression and anxiety
- Agitation and aggressive behavior
- Hallucinations
- Sleep disturbances including insomnia and somnambulism
- Irritability and restlessness 2
These neuropsychiatric events have been reported in both pediatric and adult patients taking montelukast, with different age groups showing different predominant symptoms:
- Infants (<2 years): primarily sleep disorders
- Children (2-11 years): depression/anxiety and suicidal behavior
- Adolescents (12-17 years): suicidal behavior and depression/anxiety 3
Risk Assessment and Monitoring
When considering montelukast therapy:
Baseline assessment: Document mental status and any pre-existing suicidal ideation before starting treatment to better identify medication-induced changes 4.
High-risk periods: The highest risk period for suicidal thoughts is during the first 1-2 weeks of therapy initiation, while the highest risk for suicide attempts is during the first 1-2 months of treatment 4.
Monitoring protocol:
- Monitor closely during the first 1-2 weeks of therapy
- Assess for emergence of akathisia symptoms, increased anxiety or agitation
- Watch for new or worsening suicidal thoughts
- Observe for changes in behavior, irritability, or mood worsening 4
Patient and Family Education
Patients and families should be:
- Instructed to notify their prescriber if neuropsychiatric changes occur
- Advised that montelukast is taken daily as prescribed, even during asymptomatic periods
- Informed that montelukast is not for treatment of acute asthma attacks 2
Conflicting Evidence and Research Gaps
The evidence regarding montelukast and suicide risk shows some inconsistencies:
A 2023 systematic review found no significant association between montelukast and suicide-related events in six observational studies 5.
However, pharmacovigilance data from the WHO database identified 2,630 reports of psychiatric disorders in people under 18 years taking montelukast, with suicidal behavior being over-represented in all age groups 3.
Clinical trials conducted by the manufacturer found reports of suicidality to be rare and similar between montelukast and placebo groups 6.
Clinical Decision-Making Algorithm
Initial Assessment:
- Evaluate the severity of the patient's respiratory condition
- Assess baseline mental health status and suicide risk factors
- Consider alternative treatments if the patient has a history of psychiatric disorders
Treatment Decision:
- For mild symptoms: Consider alternative treatments first
- For moderate to severe symptoms where benefits may outweigh risks:
- Start with lowest effective dose
- Implement close monitoring protocol
- Provide clear patient/family education
Monitoring Protocol:
- Weekly assessment during first month of treatment
- Direct questioning about mood changes and suicidal thoughts
- Immediate evaluation if neuropsychiatric symptoms emerge
Response to Neuropsychiatric Symptoms:
- For mild symptoms: Consider dose reduction and increased monitoring
- For moderate to severe symptoms: Discontinue medication and provide appropriate mental health referral
Conclusion
The risk of neuropsychiatric events, including suicidal thoughts and behaviors, associated with montelukast is significant enough to warrant a black box warning. While some studies show conflicting results, the FDA has determined that the potential risks require careful consideration, especially in children and adolescents. Clinicians should weigh these risks against the potential benefits, implement appropriate monitoring, and consider alternative treatments when possible, particularly for mild symptoms that can be managed with other medications.