Trazodone for Major Depressive Disorder: Treatment Recommendations
For major depressive disorder, trazodone should be initiated at 150 mg/day (predominantly given at bedtime) and titrated to 200-300 mg/day for full antidepressant efficacy. 1, 2, 3
Initial Dosing Strategy
- Start with 150 mg/day as the therapeutic starting dose, given predominantly or entirely at bedtime to leverage trazodone's sedating properties and improve tolerability 2, 3
- The once-daily formulation maintains effective blood levels for 24 hours while avoiding concentration peaks associated with side effects 1
- Bedtime dosing produces better sleep with less daytime drowsiness at treatment onset, though these differences diminish with continued use 3
Dose Titration and Therapeutic Range
- Target dose: 200-300 mg/day for full antidepressant efficacy 1, 2
- Maximum tolerated dose in elderly patients: 300-400 mg/day 4
- Younger patients may tolerate up to 600 mg/day 4
- When used as monotherapy for depression (not just sleep augmentation), doses must reach the 150-300 mg/day range—lower doses are insufficient for antidepressant effect 1, 2
Monitoring Timeline
- Begin assessing therapeutic response and adverse effects within 1-2 weeks of initiation 5
- Trazodone demonstrates early improvement in depressive symptoms within 1 week, with statistically significant reduction in Hamilton Depression Rating Scale scores compared to placebo or venlafaxine XR 6
- If inadequate response by 6-8 weeks, modify treatment 5
- Continue treatment for 4-9 months after satisfactory response in first-episode depression 5
- For patients with 2 or more depressive episodes, consider longer duration therapy (years to lifelong) 5
Specific Clinical Advantages
Trazodone is particularly well-suited for:
- Depression with insomnia: Trazodone significantly improves sleep disturbance within 7 days and does not cause tolerance or REM rebound on discontinuation 3, 6
- Depression with anorexia or weight loss: Promotes appetite and weight gain 5
- Depression with anxiety or psychomotor agitation: Low liability for activating side effects and rapid onset make it useful for these presentations 1, 2
- Patients intolerant of SSRI side effects: Avoids sexual dysfunction, insomnia, and anxiety commonly associated with SSRIs 1
Critical Safety Monitoring
- Orthostatic hypotension: Particularly in elderly patients and those with cardiovascular disease—monitor blood pressure, especially during dose titration 1, 4
- Cardiac effects: Monitor for QT prolongation and arrhythmias, especially in patients with pre-existing cardiovascular disease 1
- Priapism: Rare but serious—educate male patients to seek immediate care if erection lasts >4 hours 1, 4
- Suicidality: Monitor closely for increased suicidal thoughts, agitation, or behavioral changes, especially in the first 1-2 months 5
Common Adverse Effects
- Somnolence/sedation (most common) 1
- Headache and dizziness 1
- Xerostomia (dry mouth) 5, 1
- Minimal anticholinergic activity, low risk of weight gain and sexual dysfunction compared to other antidepressants 1, 2
When to Use Lower Doses
Important distinction: When trazodone is prescribed at 25-100 mg/day to augment another antidepressant (e.g., for SSRI-induced insomnia), these doses are subtherapeutic for depression itself 7, 2. For primary treatment of major depressive disorder, the full 150-300 mg/day range is required 1, 2.