What are the long-term risks of taking Singulair (montelukast)?

Long-Term Risks of Singulair (Montelukast)

The FDA issued a black box warning in 2020 regarding serious neuropsychiatric events associated with montelukast, including suicidal thoughts and actions, depression, anxiety, sleep disturbances, and behavioral changes—these risks should be carefully weighed against benefits, particularly in patients with mild disease that can be adequately treated with alternative medications. 1, 2, 3

Neuropsychiatric Adverse Events

The most concerning long-term risks involve neuropsychiatric effects, which appear more prevalent than initially recognized:

Mental Health Risks

• Depression and anxiety are among the most frequently reported psychiatric adverse events, with increased risk observed across all age groups 3, 4
• Suicidal behavior and completed suicide have been reported with concerning frequency, particularly in children where suicidal behavior was over-represented with information component values reaching 5.01 4
• Sleep disturbances affect approximately 15% of pediatric patients, including sleep difficulties, interruptions, decreased sleep quality, and nightmares 5
• Agitation and behavioral changes occur in approximately 10% of patients, with hyperactivity reported in 6.8% of children 5

Age-Specific Patterns

• Infants (<2 years): Predominantly experience sleep disorders 4
• Children (2-11 years): Most commonly report depression/anxiety, with completed suicides reported more frequently than in adolescents (IC: 3.15 vs 3.11) 4
• Adolescents (12-17 years): Present with suicidal behavior, depression/anxiety, and psychotic reactions more frequently 4
• Young adults (18-29 years): Show the highest risk of neuropsychiatric events requiring hospital treatment (HR 1.28) and medication initiation (HR 1.14) 6

Contradictory Evidence

One large Swedish cohort study of 74,291 children found no association between montelukast use and neuropsychiatric adverse events when compared to long-acting β-agonists (HR 0.99,95% CI 0.84-1.16) 7. However, this conflicts with multiple pharmacovigilance analyses and the FDA's determination, which led to the black box warning based on accumulated evidence of serious risks 1, 2, 3.

Other Systemic Adverse Effects

Immune and Hypersensitivity Reactions

• Churg-Strauss syndrome has been documented in case reports 8
• Anaphylaxis and eosinophilic infiltration can occur as hypersensitivity reactions 8

Hepatobiliary and Gastrointestinal Effects

• Hepatotoxicity with potentially fatal outcomes has been reported 8
• Gastrointestinal disturbances including dyspepsia (2.1%), gastroenteritis (1.5%), and abdominal pain (2.9%) occur more frequently than placebo 3
• Pancreatitis has been reported in clinical trials, though causality has not been definitively established 1

Neurological Effects Beyond Psychiatric

• Tremor, dizziness, and drowsiness have been documented 8
• Neuropathies and seizures occur rarely but represent serious adverse events 8

Clinical Context and Risk-Benefit Considerations

FDA Recommendations

The FDA explicitly states that the benefits of montelukast may not outweigh the risks, especially when disease symptoms are mild and can be adequately treated with other medications 1. This represents a significant shift in the risk-benefit assessment for this medication.

Comparative Efficacy

• Montelukast is less effective than intranasal corticosteroids for allergic rhinitis and should not be considered first-line therapy when intranasal steroids are appropriate 9
• For persistent post-adenotonsillectomy obstructive sleep apnea, evidence is limited to one small observational study showing benefit, but the FDA warning necessitates caution 1

Monitoring Requirements

Essential Surveillance

• Monitor for unusual behavioral or mood changes when starting montelukast, particularly in the first weeks of therapy 2, 10
• Screen for depression, anxiety, sleep disturbances, and suicidal ideation at each clinical encounter 3, 4
• Obtain baseline liver function tests and repeat if symptoms of hepatotoxicity develop 8

Patient and Family Counseling

• Explicitly discuss neuropsychiatric risks before initiating therapy, including the potential for suicidal thoughts and behavioral changes 1, 2
• Advise immediate discontinuation and medical evaluation if psychiatric symptoms emerge 3
• Educate about the difference between controller and rescue medications, as montelukast provides continuous control rather than acute symptom relief 9

Common Pitfalls to Avoid

• Do not prescribe montelukast for mild disease when safer alternatives like intranasal corticosteroids are available and appropriate 1, 9
• Do not dismiss psychiatric symptoms as unrelated to the medication—the FDA black box warning reflects serious, documented risks 2, 3
• Do not continue therapy without reassessing risk-benefit if any neuropsychiatric symptoms emerge, even if mild 1, 6
• Avoid use in patients with pre-existing psychiatric conditions unless benefits clearly outweigh risks, as these patients may be at higher risk 6