Drug Interaction Between Risperidone and Montelukast
There are no clinically significant pharmacokinetic or pharmacodynamic interactions documented between risperidone and montelukast, and these medications can be safely co-administered.
Metabolic Pathways and Interaction Potential
The two medications have distinct metabolic profiles that minimize interaction risk:
- Risperidone is primarily metabolized by cytochrome P450 2D6, with some contribution from CYP3A4 1
- Montelukast is metabolized by CYP3A4, 2C9, and 2C8 2
While there is minor overlap at the CYP3A4 pathway, neither drug is a potent inhibitor or inducer of these enzymes at therapeutic doses, making clinically meaningful interactions unlikely 2.
Clinical Safety Considerations
Neuropsychiatric Effects - The Primary Concern
Both medications carry independent risks of neuropsychiatric adverse effects, which theoretically could be additive:
- Risperidone can cause insomnia, agitation, anxiety, drowsiness, and orthostatic hypotension 1
- Montelukast has been associated with agitation, anxiety, depression, sleep disturbance, hallucinations, and mood disorders 3
The European Position Paper on Rhinosinusitis notes that various neuropsychiatric events have been reported with anti-leukotrienes, though evidence of causation remains conflicting 1.
Monitoring Recommendations
When prescribing these medications together, monitor for:
- Mood changes including depression, anxiety, or agitation 3
- Sleep disturbances including insomnia or vivid dreams 2, 3
- Behavioral changes particularly in pediatric or elderly populations 3
- Extrapyramidal symptoms from risperidone, especially at doses >6 mg/24h 1
Clinical Context
This combination may be encountered when treating patients with:
- Psychiatric conditions requiring risperidone (schizophrenia, bipolar disorder, behavioral disturbances)
- Concurrent asthma or allergic rhinitis requiring montelukast 1, 4
The lack of documented drug-drug interactions in the literature and absence of warnings in clinical guidelines supports the safety of this combination, provided appropriate monitoring for additive neuropsychiatric effects is maintained.
Important Caveats
- No dose adjustments are required for either medication when used together 1
- The risk of neuropsychiatric effects with montelukast appears to be idiosyncratic rather than dose-dependent 3
- Consider alternative asthma therapies (intranasal corticosteroids for rhinitis, inhaled corticosteroids for asthma) if neuropsychiatric symptoms emerge, as these are more effective first-line options anyway 1, 4