What are the potential side effects of Trazodone (triazolopyridine antidepressant) and how should it be managed?

Trazodone Side Effects and Management

Trazodone is associated with significant somnolence as its most common side effect, along with potential cardiovascular risks including orthostatic hypotension and QT prolongation, requiring careful monitoring and dose adjustment especially in patients with pre-existing cardiac conditions. 1, 2

Common Side Effects

Trazodone has several common side effects that patients and clinicians should be aware of:

• Somnolence/sedation: Most prominent side effect, higher incidence than with bupropion, fluoxetine, mirtazapine, paroxetine, or venlafaxine 2
• Gastrointestinal effects: Nausea, vomiting, diarrhea, dry mouth (xerostomia) 1, 3
• Neurological effects: Dizziness, headache 1, 3
• Other common effects: Blurred vision, swelling, tiredness, weight loss 1

Serious Adverse Effects

Several potentially serious adverse effects require special attention:

Cardiovascular Effects

• Orthostatic hypotension: Particularly concerning in elderly patients or those with heart disease 1, 4
• QT interval prolongation: May lead to torsade de pointes and cardiac arrhythmias 1, 3
• Use with caution: In patients with premature ventricular contractions 2

Other Serious Concerns

• Priapism: Painful erections lasting >6 hours requiring emergency treatment 1
• Serotonin syndrome: When combined with other serotonergic medications 1
• Increased risk of bleeding: Especially when combined with antiplatelet drugs, NSAIDs, or anticoagulants 1
• Hyponatremia: Can cause headache, confusion, memory problems, weakness 1
• Activation of mania/hypomania: In patients with bipolar disorder 1
• Discontinuation syndrome: If stopped abruptly 1

Management Approach

Initial Dosing and Titration

1. Start low: Begin with 25-50 mg daily, taken shortly after a meal or light snack 2, 1
2. Gradual titration: Increase gradually based on response and tolerability
3. Therapeutic range: 150-400 mg daily for depression, lower doses (25-100 mg) when used for insomnia 2, 3
4. Timing: Consider administering at bedtime to capitalize on sedative effects 1

Managing Specific Side Effects

For Somnolence

• Administer at bedtime to minimize daytime drowsiness 1
• Avoid activities requiring alertness until response is known 1
• Consider dose reduction if sedation is excessive 1

For Cardiovascular Effects

• Monitor blood pressure: Particularly when initiating therapy and with dose increases
• Reduce antihypertensive medications: May be necessary when used concomitantly 1
• ECG monitoring: Consider in patients with cardiac risk factors 1
• Avoid in high-risk patients: Those with pre-existing QT prolongation or taking other QT-prolonging medications 1

For Bleeding Risk

• Monitor closely: When used with antiplatelet or anticoagulant medications
• Regular coagulation testing: For patients on warfarin 1
• Educate patients: About signs of bleeding to report 1

Special Populations

Elderly Patients

• Lower starting dose: Begin with 25 mg daily
• More vigilant monitoring: For orthostatic hypotension and cognitive effects 1, 5
• Maximum dose: Generally 300-400 mg/day (versus up to 600 mg/day in younger adults) 5

Patients with Renal/Hepatic Impairment

• Dose reduction: May be necessary due to altered drug metabolism
• Closer monitoring: For adverse effects 1

Drug Interactions

Trazodone has important interactions with:

• MAOIs: Avoid concurrent use or within 14 days of discontinuing MAOIs 1
• Other serotonergic drugs: SSRIs, SNRIs, triptans (risk of serotonin syndrome) 1
• CNS depressants: Alcohol, benzodiazepines (enhanced sedation) 1
• Anticoagulants/antiplatelets: Increased bleeding risk 1
• CYP3A4 inhibitors/inducers: May affect trazodone levels 1

Monitoring Recommendations

1. Baseline assessment: Cardiac status, blood pressure, mental status
2. Regular follow-up: Blood pressure, cardiac symptoms, mood changes
3. Patient education: Report concerning symptoms (priapism, bleeding, syncope)
4. Discontinuation: Taper gradually rather than abrupt cessation 1

Clinical Pearls

• Trazodone is often used at lower doses (25-100 mg) for insomnia than for depression (150-300 mg) 3
• Unlike many antidepressants, trazodone has a low incidence of sexual dysfunction and weight gain 3
• Trazodone has minimal anticholinergic activity compared to tricyclic antidepressants 6
• The prolonged-release formulation may improve tolerability by avoiding concentration peaks associated with side effects 3
• Trazodone is relatively safe in overdose compared to tricyclic antidepressants 5

By understanding and appropriately managing these side effects, clinicians can optimize the therapeutic benefits of trazodone while minimizing risks to patients.