What are the contraindications for Trazodone (antidepressant)?

Trazodone Contraindications

Trazodone is absolutely contraindicated in patients taking or within 14 days of stopping monoamine oxidase inhibitors (MAOIs) due to increased risk of serotonin syndrome. 1

Absolute Contraindications

• MAOIs: Concurrent use or use within 14 days of MAOIs (including linezolid and intravenous methylene blue) is contraindicated due to risk of potentially fatal serotonin syndrome 1
• Pregnancy: Trazodone is contraindicated in women who are pregnant or actively trying to conceive 2

Cardiovascular Contraindications

• Cardiac arrhythmias: Trazodone should be avoided in patients with a history of cardiac arrhythmias 1
• QT prolongation: Use should be avoided in patients with known QT interval prolongation 1
• Recovery phase of myocardial infarction: Trazodone is not recommended during the initial recovery phase after a heart attack 1

Drug Interaction Contraindications

• CYP3A4 inhibitors: Concomitant use with strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, voriconazole) should be avoided due to increased risk of cardiac arrhythmias 1
• QT-prolonging medications: Avoid combination with other drugs known to prolong QT interval, including:
  • Class 1A antiarrhythmics (e.g., quinidine, procainamide) 1
  • Class 3 antiarrhythmics (e.g., amiodarone, sotalol) 1
  • Certain antipsychotics (e.g., ziprasidone, chlorpromazine, thioridazine) 1
  • Certain antibiotics (e.g., gatifloxacin) 1

Precautions (Relative Contraindications)

• Suicidal ideation: Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients (under 24 years) 1
• Serotonergic drugs: Use caution with other serotonergic medications (triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John's Wort) due to increased risk of serotonin syndrome 1
• Antiplatelet agents and anticoagulants: Concomitant use may increase bleeding risk 1
• Nursing mothers: Not recommended for use in individuals who are nursing 2
• Premature ventricular contractions (PVCs): Use with caution in patients with PVCs 2
• Narrow therapeutic index drugs: Monitor serum concentrations of digoxin or phenytoin when used concomitantly with trazodone 1
• Hypotension risk: Orthostatic hypotension and syncope have been reported; use caution, especially in elderly patients or those with heart disease 1

Clinical Considerations

• Trazodone is commonly prescribed off-label for insomnia, anxiety disorders, and other conditions beyond its FDA-approved indication for depression 3
• When used for depression, trazodone has demonstrated efficacy comparable to other antidepressants including TCAs, SSRIs, and SNRIs 4
• In elderly patients, maximum tolerated doses are typically 300-400 mg/day, while younger patients may tolerate up to 600 mg/day 5
• Drowsiness is the most common side effect, along with headache, dizziness, and dry mouth 4

Monitoring Recommendations

• Monitor for signs and symptoms of serotonin syndrome when used with other serotonergic drugs 1
• For patients taking warfarin, carefully monitor INR when initiating or discontinuing trazodone 1
• Monitor for cardiac arrhythmias in patients with pre-existing cardiac disease 1
• Close monitoring for suicidal thoughts and behaviors is essential, especially during the initial few months of treatment and at times of dosage changes 1