What are the contraindications and monitoring requirements for Trazodone (triazolopyridine antidepressant) in patients, particularly the elderly, with a history of hypersensitivity, cardiovascular disease, seizures, liver or kidney disease, and those taking other medications?

Trazodone Contraindications and Monitoring

Absolute Contraindications

Trazodone is absolutely contraindicated in patients taking MAO inhibitors (MAOIs), including linezolid or intravenous methylene blue, due to the risk of life-threatening serotonin syndrome. 1

• Active psychotic disorders are an absolute contraindication to trazodone use 2
• Known hypersensitivity to trazodone or any component of the formulation 1
• Concomitant MAOI therapy or within 14 days of discontinuing an MAOI 1

Major Precautions and Relative Contraindications

Cardiovascular Disease

Trazodone should be avoided in patients with preexisting cardiac arrhythmias, history of QT prolongation, recent myocardial infarction, symptomatic bradycardia, or conditions predisposing to torsades de pointes. 1

• Trazodone is arrhythmogenic in patients with preexisting cardiac disease, with documented cases of ventricular tachycardia, torsades de pointes, and sudden death 1, 3
• Not recommended during the initial recovery phase of myocardial infarction 1
• Avoid in patients with known QT prolongation, hypokalemia, or hypomagnesemia 1
• Use with extreme caution in patients with ventricular irritability, as trazodone may increase premature ventricular contractions 4
• Doses of 100-300 mg are better tolerated than higher doses in patients with significant cardiovascular disease 4

Drug Interactions Requiring Avoidance

Do not combine trazodone with CYP3A4 inhibitors (itraconazole, clarithromycin, voriconazole), Class 1A antiarrhythmics (quinidine, procainamide), Class 3 antiarrhythmics (amiodarone, sotalol), QT-prolonging antipsychotics (ziprasidone, chlorpromazine, thioridazine), or certain antibiotics (gatifloxacin). 1

• Serotonergic drugs (SSRIs, SNRIs, triptans, tricyclics, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John's Wort) significantly increase serotonin syndrome risk 1

Hepatic and Renal Disease

Use trazodone with caution in hepatic or renal impairment, as it has not been formally studied in these populations. 1

• Trazodone undergoes nearly complete hepatic metabolism 5
• No specific dosing adjustments are established, but lower doses are prudent 1

Seizure Disorders

Trazodone may lower the seizure threshold and should be used cautiously in patients with seizure history. 2

• Tramadol (which shares some mechanistic similarities) is contraindicated in seizure-prone patients 2
• While not an absolute contraindication for trazodone, close monitoring is essential 2

Elderly Patients

Elderly patients require lower starting doses (25-50 mg) and maximum doses of 300-400 mg/day due to increased risk of orthostatic hypotension, falls, and hyponatremia. 6

• Orthostatic hypotension and syncope are particularly problematic in the elderly 1, 6
• Elderly patients are at greater risk for clinically significant hyponatremia with serotonergic antidepressants 1
• Trazodone causes less anticholinergic effects than tricyclics, making it relatively safer in this population 6, 5

Priapism Risk

Men with conditions predisposing to priapism (sickle cell anemia, multiple myeloma, leukemia) or anatomical penile deformities should use trazodone with extreme caution. 1

• Patients must discontinue trazodone immediately if erection lasts >4 hours and seek emergency care 1

Essential Monitoring Parameters

Cardiovascular Monitoring

Obtain baseline ECG in patients with any cardiac history or risk factors, and monitor for QTc prolongation, arrhythmias, orthostatic hypotension, and heart rate changes. 1, 4

• Monitor blood pressure (supine and standing) regularly, especially during dose titration 1
• Cardiac monitoring is particularly critical in patients with preexisting ventricular irritability 3, 4
• Trazodone tends to lower heart rate, unlike many other antidepressants 4

Bleeding Risk Monitoring

Monitor coagulation indices (INR) carefully when initiating, titrating, or discontinuing trazodone in patients taking warfarin or other anticoagulants. 1

• Assess for signs of bleeding (ecchymosis, epistaxis, gastrointestinal bleeding) in patients on antiplatelet agents or NSAIDs 1

Serotonin Syndrome Surveillance

Monitor for serotonin syndrome symptoms: mental status changes (agitation, hallucinations, delirium, coma), autonomic instability (tachycardia, labile blood pressure, hyperthermia), neuromuscular symptoms (tremor, rigidity, myoclonus, hyperreflexia), seizures, and gastrointestinal symptoms. 1

• Discontinue trazodone immediately if serotonin syndrome is suspected 1

Suicidality Monitoring

Monitor all patients, especially those under age 25, for worsening depression, suicidal thoughts, or unusual behavior changes, particularly during the first few months of treatment and after dose changes. 1

• Family members and caregivers should be counseled to alert healthcare providers of behavioral changes 1

Electrolyte Monitoring

Check serum sodium periodically, especially in elderly patients, those on diuretics, or with volume depletion. 1

Hepatic and Renal Function

Monitor liver and kidney function periodically in patients with preexisting hepatic or renal disease. 1

Dosing Considerations

Start with 150 mg/day in divided doses for adults, with maximum doses of 400 mg/day for outpatients and 600 mg/day for inpatients. 7

• Elderly patients should start at lower doses (25-50 mg) with maximum of 300-400 mg/day 6
• The prolonged-release formulation (TzCOAD) may improve tolerability 7
• Food delays absorption but does not affect total drug exposure 5