What is the risk of depression and suicidal thoughts in patients with a history of respiratory issues, such as asthma or allergic rhinitis, taking montelukast (Singulair)?

Neuropsychiatric Risks of Montelukast: Depression and Suicidal Ideation

The FDA-mandated boxed warning for montelukast explicitly states that neuropsychiatric events including agitation, depression, suicidal thinking and behavior (including suicide) have been reported, and prescribers must carefully evaluate risks versus benefits before initiating treatment, particularly given that alternative therapies (intranasal corticosteroids for rhinitis, inhaled corticosteroids for asthma) are more effective and lack these serious psychiatric risks. 1

FDA-Documented Neuropsychiatric Events

The FDA drug label documents the following psychiatric adverse events reported with montelukast use 1:

• Suicidal thinking and behavior, including completed suicide
• Depression
• Agitation, including aggressive behavior or hostility
• Anxiousness and anxiety
• Dream abnormalities and bad/vivid dreams
• Hallucinations
• Irritability and restlessness
• Sleep walking (somnambulism)
• Tremor and insomnia

The FDA requires that patients and prescribers remain alert for neuropsychiatric events, and patients must notify their prescriber immediately if these changes occur. 1

Quantified Risk from Recent Research

The most rigorous 2022 propensity-matched cohort study of 154,946 patients found statistically significant increased odds of neuropsychiatric diagnoses within 12 months of montelukast initiation 2:

• Asthma patients: 11% increased odds (OR 1.11,95% CI 1.04-1.19) of any neuropsychiatric outcome
• Allergic rhinitis patients: 7% increased odds (OR 1.07,95% CI 1.01-1.14) of any neuropsychiatric outcome
• Anxiety disorders showed the highest risk in asthma patients (OR 1.21,95% CI 1.05-1.20)
• Insomnia showed elevated risk in allergic rhinitis patients (OR 1.15,95% CI 1.05-1.27)

A 2025 meta-analysis confirmed montelukast treatment was associated with 11% higher risk of anxiety (RR 1.11,95% CI 1.06-1.16), though no consistent evidence emerged for depression or suicidal behaviors due to limited data. 3

Critical Context: Conflicting Evidence on Causation

A 2018 Danish nationwide symmetry analysis of 4,450 patients found only a weak association (sequence ratio 1.21,95% CI 1.14-1.28) between montelukast and antidepressant prescriptions, with stratified analyses suggesting the association may relate to underlying asthma severity rather than montelukast itself. 4 This study design specifically controls for confounding by indication, making it methodologically stronger for assessing causation than standard cohort studies.

However, the FDA boxed warning emphasizes that "the clinical details of some post-marketing reports involving montelukast appear consistent with a drug-induced effect," suggesting true causation in at least some cases. 1

Clinical Algorithm for Prescribing Decisions

Given the documented neuropsychiatric risks and availability of superior alternatives, montelukast should be reserved for specific scenarios only:

When NOT to Prescribe Montelukast

• First-line treatment for allergic rhinitis - intranasal corticosteroids are more effective and lack psychiatric risks 5, 6
• First-line treatment for asthma - inhaled corticosteroids are superior 7
• Patients with current or prior psychiatric illness - the 2022 study recommends monitoring particularly in those with history of mental health problems 2
• Patients with prior suicidal ideation or attempts - absolute contraindication given FDA suicide reports 1

When Montelukast May Be Considered

• Patients with both asthma and allergic rhinitis who refuse or cannot tolerate intranasal/inhaled corticosteroids (addresses both conditions simultaneously) 5, 6, 8
• "Steroid-phobic" patients or parents as alternative therapy 6
• After intranasal corticosteroids have failed for allergic rhinitis 5

Mandatory Monitoring Protocol

If montelukast is prescribed despite these risks, the FDA requires 1:

1. Explicit patient counseling about suicide risk, depression, anxiety, sleep disturbances, and behavioral changes before first dose
2. Instruction to stop medication immediately and contact prescriber if any neuropsychiatric symptoms develop
3. Regular screening at follow-up visits for mood changes, sleep problems, behavioral changes
4. Immediate discontinuation if any neuropsychiatric event occurs - do not attempt to "monitor through it"

Common Prescribing Pitfalls to Avoid

The Austrian working group of pediatric pulmonology explicitly states that treatment should be stopped immediately upon occurrence of ANY neuropsychiatric side effects - there is no role for continued monitoring while symptomatic. 9

Do not prescribe montelukast as first-line for isolated allergic rhinitis - this violates guideline recommendations, wastes resources, and exposes patients to unnecessary psychiatric risk when intranasal corticosteroids are both safer and more effective. 5, 6

Do not minimize the boxed warning - while the 2018 Danish study suggests confounding by asthma severity may explain some associations 4, the FDA determination that some cases appear "consistent with a drug-induced effect" means true causation occurs in at least a subset of patients. 1