Risperidone and Amitriptyline Interaction
Drug interaction information between Risperidone and Amitriptyline.
Risperidone and Amitriptyline have a documented major interaction in FDA labeling.
FDA drug labeling documents a major-severity interaction between Risperidone and Amitriptyline. Major interactions are generally avoided, moderate ones may need monitoring or a dose adjustment, and minor ones are usually low-risk. This page shows the documented mechanism and guidance. Label-documented interactions are not a complete safety review, so always confirm your own medications with a pharmacist or doctor. Educational information, not medical advice.
How They Interact
Amitriptyline causes a very small increase in risperidone levels in the body, but the change is not large enough to be significant.
What To Do
No dose adjustment is needed when these two medications are taken together.
FDA Label Information
Dose adjustment is not recommended for risperidone tablets when co-administered with ranitidine, cimetidine, amitriptyline, or erythromycin [see Table 18 ] . Do not exceed twice the patient’s usual dose Enzyme (CYP3A) inhibitors Ranitidine 150 mg twice daily 1 mg single dose 1.2 1.4 Dose adjustment not needed Cimetidine 400 mg twice daily 1 mg single dose 1.1 1.3 Dose adjustment not needed Erythromycin 500 mg four times daily 1 mg single dose 1.1 0.94 Dose adjustment not needed Other Drugs Amitriptyline 50 mg twice daily 3 mg twice daily 1.2 1.1 Dose adjustment not Needed *Change relative...
Risperidone Also Interacts With
- Carbamazepine major
- Lithium major
- Erythromycin major
- Ranitidine major
- Cimetidine major
Amitriptyline Also Interacts With
- Sertraline minor
- Fluoxetine minor
- Paroxetine minor
- Disulfiram minor
- Flecainide minor
Frequently Asked Questions
Can I take Risperidone and Amitriptyline together?
This is a major interaction. No dose adjustment is needed when these two medications are taken together.
How serious is the interaction between Risperidone and Amitriptyline?
This interaction is classified as "major" severity by the FDA. Major interactions may be life-threatening or cause serious side effects.
Why do Risperidone and Amitriptyline interact?
Amitriptyline causes a very small increase in risperidone levels in the body, but the change is not large enough to be significant.
Understanding the Risperidone and Amitriptyline Interaction
FDA-approved prescribing information for these two drugs flags their combination as a major-severity interaction. Risperidone belongs to the Atypical Antipsychotic class and Amitriptyline belongs to the Tricyclic Antidepressant (TCA) class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: Amitriptyline causes a very small increase in risperidone levels in the body, but the change is not large enough to be significant. Severity tiers matter: major flags generally advise avoidance, moderate flags often require monitoring or dose adjustment, and minor flags may only call for awareness.
Context around a specific patient determines real-world impact. Risperidone has 20 total documented interactions on file in this dataset, and Amitriptyline has 21. Each additional medication compounds the interaction surface, which is why pharmacists run full-profile checks rather than evaluating one pair at a time. FDA-derived guidance for this pair is: No dose adjustment is needed when these two medications are taken together. Timing of doses, renal and hepatic function, age, and other concurrent prescriptions all shape whether a labeled interaction matters clinically.
An interaction flag is not a verdict. A large share of labeled interactions are managed routinely in clinical practice, the fix may be as simple as spacing doses or adding a monitoring test. Others require the prescriber to choose a different medication entirely. This page surfaces FDA-sourced labeling and openFDA data for educational purposes only; it is not medical advice and cannot account for your full clinical picture. Never start, stop, or adjust either Risperidone or Amitriptyline based on a web page, speak with your prescriber or pharmacist before making any change.
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. Always consult your healthcare provider about drug interactions.
Read our methodology - how this data is sourced, computed, and verified.