Does Montelukast Cause Tiredness and Fatigue?
No, montelukast does not typically cause tiredness or fatigue as a direct adverse effect; in fact, clinical evidence demonstrates that montelukast can actually reduce fatigue and daytime somnolence by improving sleep quality in patients with allergic rhinitis. 1, 2
Evidence from FDA Drug Labeling
The FDA-approved prescribing information for montelukast (Singulair) does not list tiredness or fatigue as common adverse effects 1. The most frequently reported adverse effects include:
- Upper respiratory infection (1.9% vs 1.5% placebo) 1
- Headache, otitis media, pharyngitis 1
- Abdominal pain, nausea, vomiting 1
- Drowsiness (somnolence) is specifically noted to occur at rates similar to placebo 1
Paradoxical Benefit: Montelukast May Actually Reduce Fatigue
A well-designed, double-blind, placebo-controlled study in patients with perennial allergic rhinitis demonstrated that montelukast significantly improved daytime somnolence (p = 0.0089) and daytime fatigue (p = 0.0087) compared to placebo 2. This improvement occurred because montelukast reduced nasal congestion, which in turn improved sleep quality and reduced the fatigue associated with poor sleep 2.
Neuropsychiatric Effects: The Real Concern
While fatigue is not a typical side effect, montelukast carries an FDA black box warning for serious neuropsychiatric events 3, 4. The documented neuropsychiatric adverse effects include:
- Sleep disturbances: insomnia, nightmares, sleepwalking, sleeptalking 1, 5, 6, 7
- Agitation, aggressive behavior, hostility 1, 6
- Depression, anxiety, suicidal thoughts and behavior 1, 6
- Irritability, restlessness 1
Important Clinical Distinction
In a pediatric case series, insomnia was the most frequently reported adverse effect (35% of patients with adverse reactions), not fatigue or excessive sleepiness 5. When sleep-related problems occur with montelukast, they typically manifest as difficulty sleeping (insomnia) rather than excessive tiredness 5, 6.
Clinical Algorithm for Evaluating Fatigue in Patients Taking Montelukast
If a patient on montelukast reports fatigue, consider the following:
Assess for paradoxical insomnia: Ask specifically about difficulty falling asleep, nightmares, or sleep disruption, as these are documented montelukast side effects that could secondarily cause daytime fatigue 1, 5, 6
Evaluate the underlying condition: Uncontrolled allergic rhinitis or asthma itself causes fatigue through sleep disruption from nasal congestion and respiratory symptoms 2
Review for other neuropsychiatric symptoms: Depression and anxiety (documented montelukast side effects) commonly present with fatigue 1, 6
Consider alternative causes: The fatigue is more likely related to the underlying disease, concurrent medications, or other medical conditions rather than montelukast directly 1
Pediatric Considerations
In a large multicenter study of 689 children aged 2-5 years treated with montelukast for 12 weeks, there were no clinically meaningful differences in adverse effects between montelukast and placebo groups 8. The safety profile was excellent, with approximately 90% of patients completing the study 8. When adverse reactions do occur in children, they typically involve sleep disturbances (insomnia, nightmares) rather than excessive tiredness 5.
Key Clinical Caveat
If a patient develops new-onset fatigue after starting montelukast, first investigate for insomnia or other sleep disturbances (documented side effects) that could be causing secondary daytime fatigue, rather than attributing the fatigue directly to the medication 1, 5, 6. The FDA recommends monitoring all patients for unusual behavioral or mood changes when starting montelukast 3.