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, agitation, nightmares, insomnia, and anxiety, and patients should be monitored for these symptoms, especially during the first weeks of treatment or after dose changes 1.

Psychiatric Concerns with Montelukast

The FDA has issued a boxed warning for montelukast due to reports of neuropsychiatric events, which can occur in both adults and children, with children potentially being more vulnerable.

• Patients taking montelukast should be informed about these potential side effects before starting treatment.
• Those with pre-existing psychiatric conditions may need closer monitoring.
• Alternative asthma or allergy medications might be preferable for patients with psychiatric histories or those who develop psychiatric symptoms while on montelukast.

Mechanism and Monitoring

The mechanism behind these psychiatric effects isn't fully understood but may involve montelukast crossing the blood-brain barrier and affecting leukotriene receptors in the brain, which play roles in neuroinflammation and neuropsychiatric function 1.

• If psychiatric symptoms develop, discontinuation of montelukast should be considered, with appropriate psychiatric evaluation if needed.
• Patients should be monitored for mood changes, behavioral disturbances, or suicidal thoughts, especially during the first weeks of treatment or after dose changes.

Clinical Considerations

While the provided evidence does not directly address the psychiatric concerns of montelukast, it highlights the importance of considering the potential risks and benefits of medication use, particularly in vulnerable populations such as pregnant women and children 1.

• Healthcare providers should weigh the potential benefits of montelukast against the potential risks of psychiatric side effects when making treatment decisions.
• Close monitoring and open communication with patients and their families are essential for minimizing the risks associated with montelukast use.

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.