Understanding Trazodone and Its Mechanism
Trazodone, an antidepressant for major depressive disorder and often prescribed off-label for insomnia due to its sedative effects, increases serotonin levels in the brain. It is metabolized by liver enzymes, primarily CYP3A4, which makes it susceptible to interactions with various substances. These interactions can lead to reduced effectiveness or, more seriously, increased side effects.
Absolute Contraindications: Monoamine Oxidase Inhibitors (MAOIs)
The most severe interaction is with Monoamine Oxidase Inhibitors (MAOIs). Combining trazodone with MAOIs, or within 14 days of stopping one, can cause serotonin syndrome, a life-threatening condition from excessive serotonin. Symptoms include agitation, confusion, rapid heart rate, and fever. Avoid MAOIs such as isocarboxazid, phenelzine, selegiline, and tranylcypromine, as well as linezolid and methylene blue which have MAOI properties.
High-Risk Drug Interactions
Numerous other drugs also pose significant risks when combined with trazodone. Always inform your healthcare provider about all medications you take.
Other Serotonergic Drugs
Combining trazodone with drugs that also increase serotonin levels greatly increases the risk of serotonin syndrome. This includes other antidepressants like SSRIs and SNRIs, opioid pain relievers such as tramadol, and migraine medications (triptans). The herbal supplement St. John's wort also poses this risk.
Medications Affecting Heart Rhythm
Trazodone can prolong the QT interval, potentially causing serious irregular heartbeats. This risk is elevated when taken with other QT-prolonging drugs. These include certain antiarrhythmics (e.g., amiodarone, sotalol), antipsychotics (e.g., ziprasidone), and some antibiotics (e.g., clarithromycin).
Blood Thinners and Drugs that Increase Bleeding Risk
Combining trazodone with blood thinners or other medications that affect blood clotting increases the risk of bleeding. This includes anticoagulants like warfarin, antiplatelet drugs such as aspirin, and NSAIDs like ibuprofen.
CYP3A4 Inhibitors and Inducers
Since trazodone is metabolized by the CYP3A4 enzyme, other drugs affecting this enzyme can impact trazodone levels. CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) can increase trazodone levels, raising side effect risks, potentially requiring a lower trazodone dose. CYP3A4 inducers (e.g., carbamazepine, phenytoin) can decrease trazodone levels, reducing its effectiveness, and might require a higher trazodone dose.
Comparison of Major Trazodone Interactions
| Interacting Drug Class | Key Examples | Primary Risk | Management |
|---|---|---|---|
| MAOIs | Phenelzine, Selegiline, Linezolid | Serotonin Syndrome | Strictly contraindicated. Must have a 14-day washout period between drugs. |
| Other Antidepressants (SSRIs, SNRIs) | Sertraline, Fluoxetine, Duloxetine | Serotonin Syndrome | Avoid if possible; requires close monitoring if combined. |
| Blood Thinners & NSAIDs | Warfarin, Apixaban, Ibuprofen, Aspirin | Increased Bleeding | Monitor for signs of bleeding; may require dose adjustment or alternative medication. |
| QT-Prolonging Drugs | Amiodarone, Sotalol, Ziprasidone | Cardiac Arrhythmias | Avoid combination, especially in patients with pre-existing heart conditions. |
| Strong CYP3A4 Inhibitors | Ketoconazole, Ritonavir, Clarithromycin | Increased Trazodone Levels & Side Effects | Consider a lower dose of trazodone. |
| Strong CYP3A4 Inducers | Carbamazepine, Phenytoin, Rifampin | Decreased Trazodone Efficacy | Monitor for effectiveness; may need an increased trazodone dose. |
Other Important Interactions
- Alcohol: Combining trazodone with alcohol, both CNS depressants, can cause severe drowsiness, dizziness, and dangerous respiratory depression, increasing overdose risk.
- Grapefruit Juice: Grapefruit inhibits the CYP3A4 enzyme, potentially increasing trazodone levels and side effect risks, including heart rhythm changes. Avoiding grapefruit products is recommended.
- Other CNS Depressants: Combining trazodone with benzodiazepines, sleeping pills, or muscle relaxers can cause excessive sedation.
- Digoxin and Phenytoin: Trazodone can increase levels of digoxin and phenytoin, drugs with a narrow safety margin, increasing toxicity risk.
Conclusion
Avoiding dangerous drug interactions with trazodone is vital for safety. The most critical interactions involve MAOIs, other serotonergic drugs, medications affecting heart rhythm, and blood thinners. Common substances like alcohol and grapefruit juice also pose risks. Always provide your healthcare provider with a complete list of all substances you are taking to ensure safe treatment.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always consult with a qualified healthcare professional before starting, stopping, or changing any medication.
Authoritative Link: Learn more about Trazodone from the National Library of Medicine
