What Not to Mix with Trazodone: Essential Safety Tips
Trazodone is a commonly prescribed medication for anxiety, depression, and sleep disorders in both humans and veterinary patients such as dogs. While effective, trazodone can interact adversely with a variety of substances, leading to serious health complications. Understanding which substances must be avoided is essential for safe treatment.
1. Alcohol
Combining trazodone with alcohol is strongly discouraged. Alcohol increases the sedative effects of trazodone, which may lead to extreme drowsiness, dizziness, respiratory depression, or even unconsciousness. Additionally, alcohol may worsen the conditions that trazodone is meant to treat, such as anxiety or depression.
2. Other Sedatives
Benzodiazepines (e.g., diazepam, lorazepam), barbiturates, and other CNS depressants can dangerously amplify trazodone’s sedative effects. When used together, these drugs may lead to:
- Excessive sedation
- Respiratory depression
- Confusion or motor impairment
Veterinarians must be cautious when prescribing trazodone along with other sedatives in pets.
3. Monoamine Oxidase Inhibitors (MAOIs)
MAOIs like phenelzine or selegiline react seriously with trazodone. These interactions can cause serotonin syndrome, a potentially life-threatening condition. Symptoms include:
- Agitation
- Rapid heart rate
- Increased blood pressure
- Tremors or seizures
To avoid such reactions, trazodone should not be started until at least two weeks after discontinuing an MAOI.
4. Selective Serotonin Reuptake Inhibitors (SSRIs)
Though often prescribed concurrently under supervision, SSRIs such as fluoxetine or sertraline can increase the risk of serotonin syndrome when taken with trazodone. This risk necessitates careful dose management and monitoring of symptoms.
5. Drugs That Affect QT Interval
Trazodone can prolong the QT interval on an ECG, which increases the risk of life-threatening arrhythmias, particularly torsades de pointes. Drugs that also prolong QT—such as some antipsychotics, antibiotics (like erythromycin), and antiarrhythmics—should not be used unless absolutely necessary and under strict medical supervision.
6. CYP3A4 Inhibitors
Trazodone is metabolized in the liver by the CYP3A4 enzyme. Drugs that inhibit this enzyme can increase trazodone blood levels and its associated side effects. Examples include:
- Ketoconazole
- Ritonavir
- Clarithromycin
When such drugs are necessary, dosing adjustments and monitoring are essential.
7. Recreational Drugs
Illegal substances like cocaine, ecstasy (MDMA), or LSD can profoundly affect serotonin levels. In combination with trazodone, they might trigger serotonin syndrome or other neurological risks.
8. Herbal and Over-the-Counter Supplements
Even over-the-counter and herbal supplements can pose risks. Avoid combining trazodone with:
- St. John’s Wort – increases serotonin risk
- Melatonin or valerian – increases sedation
- Diphenhydramine (Benadryl) – heightens drowsiness
Managing Medication Safety
Whether administering trazodone to yourself or a pet, always disclose all medications, supplements, or herbs to your healthcare provider or veterinarian. Sudden changes in behavior or physical health after starting trazodone could indicate a dangerous interaction. Key strategies for avoiding problems include:
- Careful medication review before starting trazodone
- Gradual dose adjustments
- Regular monitoring of side effects
- Readily available emergency contacts
The Bottom Line
Trazodone is beneficial for managing anxiety and sleep issues when used properly, but its interactions with numerous substances can be harmful—or even fatal—if not carefully managed. By understanding what cannot be mixed with trazodone and following professional advice, users and pet owners can promote safety and wellbeing.
