Management of Mood Problems with Montelukast (Singulair)
Discontinue montelukast immediately if the patient develops depression, anxiety, irritability, or suicidal thoughts, and contact a healthcare provider right away. 1
Immediate Action Required
Stop montelukast immediately if any neuropsychiatric symptoms emerge, including agitation, aggressive behavior, anxiousness, depression, disorientation, hallucinations, insomnia, irritability, obsessive-compulsive symptoms, restlessness, suicidal thoughts and behavior (including suicide), or tremor 1
Contact a healthcare provider immediately when changes in behavior or thinking that are not typical for the patient occur, or if suicidal ideation or suicidal behavior develops 1
Continue monitoring and provide supportive care until symptoms resolve, as in some cases symptoms have persisted after montelukast discontinuation 1
Clinical Context and Evidence
The FDA issued a boxed warning about serious neuropsychiatric events with montelukast, which have been reported in patients with and without previous psychiatric history 1. These events have occurred mostly during treatment but also after discontinuation 1.
Key neuropsychiatric risks include:
- Depression and depressive symptoms 1
- Anxiety and anxiousness 1
- Suicidal thoughts and behavior, including completed suicide 1, 2
- Aggressive behavior or hostility 1
- Sleep disturbances and abnormal dreams 1
- Hallucinations and psychotic-like symptoms 1
Recent observational data shows montelukast exposure is associated with increased neuropsychiatric events, particularly in younger patients. A nationwide Danish cohort study found montelukast use was significantly associated with use of neuropsychiatric medications (HR 1.14; 95% CI: 1.08-1.20), with the highest risk in patients aged 18-29 years 3. A cross-sectional analysis of NHANES data demonstrated montelukast exposure was associated with depression (OR 1.61; 95% CI: 1.18-2.19) 4.
However, it's important to note that a 2025 Swedish nationwide cohort study of 74,291 children found no association between montelukast use and neuropsychiatric adverse events compared to LABA users (weighted HR 0.99; 95% CI: 0.84-1.16) 5. This suggests the evidence remains somewhat mixed, though the FDA warning and drug label take precedence in clinical decision-making.
Prevention Strategy
Reserve montelukast only for patients with allergic rhinitis who have inadequate response or intolerance to intranasal corticosteroids 6, 1. For asthma, inhaled corticosteroids are preferred as first-line maintenance therapy over leukotriene receptor antagonists 6.
Before prescribing montelukast:
- Discuss the benefits and risks with patients and caregivers, emphasizing the neuropsychiatric warning 1
- Advise patients and caregivers to be alert for behavioral changes or new neuropsychiatric symptoms 1
- Consider that the benefits may not outweigh risks when symptoms are mild and adequately treated with alternative therapies 1
Re-evaluation After Discontinuation
Carefully re-evaluate the benefits and risks before restarting montelukast if neuropsychiatric events occurred 1. Given the FDA boxed warning and available evidence showing increased risk in certain populations, alternative therapies should be strongly considered rather than rechallenge with montelukast 1, 3.