What are the contraindications for Trazodone (antidepressant medication)?

Trazodone Contraindications

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

Primary Contraindications

• Concurrent use with MAOIs: This includes prescription MAOIs (isocarboxazid, phenelzine, tranylcypromine) as well as linezolid (antibiotic) and intravenous methylene blue 1
• Pregnancy and breastfeeding: Trazodone is contraindicated in women who are pregnant or actively trying to conceive, and not recommended for use in women who are nursing 2
• History of cardiac arrhythmias: Trazodone should be avoided in patients with a history of cardiac arrhythmias due to risk of QT prolongation and torsade de pointes 1

Precautions and Relative Contraindications

• Preexisting cardiac disease: Clinical studies indicate trazodone may be arrhythmogenic in patients with preexisting cardiac disease, with reports of isolated PVCs, ventricular couplets, and tachycardia with syncope 1
• QT interval prolongation: Trazodone prolongs the QT/QTc interval and should be avoided in patients with known QT prolongation 1
• Initial recovery phase of myocardial infarction: Trazodone is not recommended during this period 1
• Concomitant use with drugs that prolong QT interval: Including Class 1A antiarrhythmics (quinidine, procainamide), Class 3 antiarrhythmics (amiodarone, sotalol), certain antipsychotics (ziprasidone, chlorpromazine, thioridazine), and certain antibiotics (gatifloxacin) 1
• Strong CYP3A4 inhibitors: Concomitant use with strong CYP3A4 inhibitors (itraconazole, ketoconazole, clarithromycin, indinavir) increases trazodone exposure and risk of adverse reactions 1
• Premature ventricular contractions: Use with caution in patients with PVCs 2
• Suicidal ideation risk: Increased risk in pediatric and young adult patients (under 24 years) 1

Drug Interactions Requiring Caution

• Antiplatelet agents and anticoagulants: Concurrent use may potentiate the risk of bleeding 1
• Other serotonergic drugs: Triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort can increase risk of serotonin syndrome 1
• Digoxin and phenytoin: Trazodone can increase concentrations of these narrow therapeutic index drugs 1
• CYP3A4 inducers: Drugs like rifampin, carbamazepine, phenytoin, and St. John's Wort may decrease trazodone exposure 1
• Antihypertensives: Concomitant use may require dose reduction of the antihypertensive drug due to risk of orthostatic hypotension 1

Special Population Considerations

• Elderly patients: Higher risk of orthostatic hypotension; lower doses are recommended 1, 3
• Hepatic impairment: Dose adjustment may be necessary due to altered metabolism 1
• Women of reproductive potential: Must be counseled regarding reliable contraception methods 2
• Patients with seizure disorders: Use with caution due to potential lowering of seizure threshold 1

Monitoring Recommendations

• Cardiac monitoring: Particularly in patients with cardiac risk factors or when combining with other medications that affect cardiac function 1
• Signs of serotonin syndrome: Mental status changes, autonomic instability, neuromuscular symptoms, seizures, and gastrointestinal symptoms 1
• Suicidal thoughts and behaviors: Especially during initial few months of therapy and at times of dosage changes 1
• Orthostatic hypotension: Monitor blood pressure when initiating therapy or changing doses, particularly in elderly patients 1

By understanding these contraindications and taking appropriate precautions, clinicians can safely prescribe trazodone while minimizing risks to patients.