What are the psychiatric concerns associated with Montelukast (Singulair)?

From the Guidelines

Montelukast has been associated with psychiatric side effects, including depression, suicidal thoughts, aggression, anxiety, nightmares, insomnia, and irritability, and patients taking this medication should be closely monitored for these symptoms. The FDA has issued a boxed warning for montelukast due to reports of neuropsychiatric events 1. Patients taking montelukast, particularly children, should be monitored closely for mood changes, behavioral disturbances, or suicidal thoughts. If these symptoms develop, discontinuation of the medication should be considered, with appropriate psychiatric evaluation if needed.

Key Considerations

• The mechanism behind these effects is not fully understood but may involve montelukast crossing the blood-brain barrier and affecting leukotriene receptors in the brain, which play a role in neuroinflammation and neuropsychiatric function.
• Before starting montelukast, patients should be informed of these potential risks, and alternative asthma or allergy medications should be considered for patients with pre-existing psychiatric conditions or those who develop psychiatric symptoms while on the medication.
• Montelukast is a Pregnancy Category B drug, and while there are reassuring animal reproductive studies and unpublished human safety data, its use during pregnancy should be carefully considered 1.

Monitoring and Management

• Patients taking montelukast should be closely monitored for psychiatric side effects, particularly during the initial treatment period.
• If psychiatric symptoms develop, discontinuation of the medication should be considered, and alternative treatments should be explored.
• Patients with pre-existing psychiatric conditions should be carefully evaluated before starting montelukast, and alternative medications should be considered if possible.

Alternative Treatments

• Other asthma or allergy medications, such as inhaled corticosteroids, may be considered as alternative treatments for patients with pre-existing psychiatric conditions or those who develop psychiatric symptoms while on montelukast 1.
• The choice of alternative treatment should be based on the individual patient's needs and medical history.

From the FDA Drug Label

Neuropsychiatric events have been reported in adult, adolescent, and pediatric patients taking SINGULAIR Post-marketing reports with SINGULAIR use include agitation, aggressive behavior or hostility, anxiousness, depression, dream abnormalities, hallucinations, insomnia, irritability, restlessness, somnambulism, suicidal thinking and behavior (including suicide), and tremor. Psychiatric disorders: agitation including aggressive behavior or hostility, anxiousness, depression, dream abnormalities, hallucinations, insomnia, irritability, restlessness, somnambulism, suicidal thinking and behavior (including suicide), tremor

Montelukast psychiatric concerns are a significant issue, with reports of various neuropsychiatric events in patients taking the medication, including:

• Agitation
• Aggressive behavior or hostility
• Anxiousness
• Depression
• Dream abnormalities
• Hallucinations
• Insomnia
• Irritability
• Restlessness
• Somnambulism
• Suicidal thinking and behavior (including suicide)
• Tremor Patients and prescribers should be alert for these events, and prescribers should carefully evaluate the risks and benefits of continuing treatment with SINGULAIR if such events occur 2 2.

From the Research

Montelukast Psychiatric Concerns

• The association between montelukast use and psychiatric adverse events has been investigated in several studies 3, 4, 5, 6, 7.
• A study published in 2021 found that exposure to montelukast was associated with a lower risk of treated outpatient depressive disorder, and no increased risks of inpatient depressive disorder, self-harm, or suicide were observed compared to inhaled corticosteroid use 3.
• In contrast, a 2023 study found that initiation of montelukast was significantly associated with the use of neuropsychiatric medicine, and a significant risk associated with montelukast initiation was found only in the youngest age groups for hospital contacts with a neuropsychiatric diagnosis 4.
• A systematic review published in 2023 found that montelukast is not associated with suicide- and depression-related events in asthma patients, but older adults may be particularly susceptible to anxiety and sleeping disorders 5.
• A study published in 2022 found that montelukast interferes with the glutathione detoxification system in the brain and dysregulates various neurotransmitter and neurosteroid pathways, which may explain the observed neuropsychiatric reactions 6.
• A 2025 study found no association between the use of montelukast and the risk of neuropsychiatric adverse events in children and adolescents, with consistent results across subgroups and sensitivity analyses 7.

Key Findings

• The risk of psychiatric adverse events associated with montelukast use may vary depending on age, with younger individuals potentially being at higher risk 4, 6.
• Montelukast may interfere with brain chemistry and contribute to neuropsychiatric adverse events, particularly in children and adolescents 6.
• The evidence on the association between montelukast use and psychiatric adverse events is conflicting, and further research is needed to fully understand the relationship 3, 4, 5, 7.

Age-Related Effects

• Age-stratified analyses have shown that the risk of neuropsychiatric events associated with montelukast use increases with decreasing age, with the highest risk seen in patients aged 18 to 29 years 4.
• Children and adolescents may be particularly susceptible to the neuropsychiatric effects of montelukast due to the early maturation stage of their brains 6.
• Older adults may be at higher risk of anxiety and sleeping disorders associated with montelukast use 5.