What is the relationship between Montelukast (Singulair) and mental health?

From the Guidelines

Montelukast has been associated with mental health side effects, including depression, anxiety, and suicidal thoughts, and patients taking this medication should be closely monitored for these symptoms. The evidence from various studies, including those referenced in 1 and 1, suggests that montelukast can have neuropsychiatric effects, although the exact mechanism is not fully understood.

Key Points to Consider

• The FDA added a boxed warning about these mental health risks in 2020, reflecting the seriousness of these potential side effects 1.
• Montelukast can cause a range of mental health symptoms, including depression, anxiety, sleep disturbances, behavioral changes, and in rare cases, suicidal thoughts.
• These side effects appear more common in children but can affect adults as well.
• If patients experience any mood changes, agitation, aggression, hallucinations, or suicidal thoughts while taking montelukast, they should contact their healthcare provider immediately.
• The mechanism behind these effects likely involves montelukast crossing the blood-brain barrier and affecting leukotriene receptors in the brain, which may influence neurological function.

Alternative Treatments

• Inhaled corticosteroids or antihistamines may be considered as alternative medications for patients who are concerned about the mental health risks associated with montelukast 1.
• Studies have shown that combining leukotriene receptor antagonists and inhaled corticosteroids can be an effective treatment for moderate persistent asthma, but patients should be closely monitored for any potential side effects 1.

From the FDA Drug Label

Psychiatric disorders: agitation including aggressive behavior or hostility, anxiousness, depression, dream abnormalities, hallucinations, insomnia, irritability, restlessness, somnambulism, suicidal thinking and behavior (including suicide), tremor 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.

Mental Health and Montelukast:

• Montelukast has been associated with neuropsychiatric events, including agitation, aggressive behavior, anxiousness, depression, and suicidal thinking and behavior.
• These events have been reported in adult, adolescent, and pediatric patients taking montelukast.
• Patients and prescribers should be alert for neuropsychiatric events and carefully evaluate the risks and benefits of continuing treatment with montelukast if such events occur 2, 2.

From the Research

Montelukast and Mental Health

• The relationship between montelukast and mental health has been investigated in several studies, with conflicting results 3, 4, 5.
• A study published in 2021 found that exposure to montelukast was associated with a lower risk of treated outpatient depressive disorder, but no increased risks of inpatient depressive disorder, self-harm, or suicide were observed compared to inhaled corticosteroid use 3.
• In contrast, a 2024 study found that montelukast exposure was associated with a higher prevalence of depression, and network pharmacology identified multiple pathways through which montelukast may contribute to depression 5.
• Another study published in 2009 found that there was insufficient data to prove a link between montelukast and suicidality, and recommended that inquiring about mood changes and suicidal ideation should be integrated into general medical practice 4.

Barriers to Exercise and Mental Health

• Exercise has been shown to have positive effects on mental health, but people with severe mental illnesses may face barriers to exercise, including psychiatric medication side effects, symptoms related to severe mental illnesses, and physical comorbidities 6.
• A 2024 study found that mental health professionals had more knowledge about the positive effects of exercise on general health than patients, and that exercise was prescribed mostly or always by mental health professionals 7.
• The study also found that male patients were more likely to experience exercise as a positive distraction and had lower physical health barriers than female patients 7.

Implications for Montelukast Use and Mental Health

• The available evidence suggests that montelukast may be associated with an increased risk of depression, but the relationship between montelukast and mental health is complex and requires further study 3, 5.
• Clinicians should be aware of the potential risks and benefits of montelukast use in patients with mental health conditions, and consider alternative treatments or monitoring strategies as needed 3, 4, 5.