What is the recommended dosage and treatment approach for Trazodone (antidepressant) in patients with major depressive disorder?

Trazodone Dosage and Treatment Approach for Major Depressive Disorder

For major depressive disorder, trazodone is recommended at dosages of 150-300 mg/day, typically administered predominantly at bedtime to maximize efficacy while minimizing side effects. 1, 2

Dosing Recommendations

• Initial dosing should start at 150 mg given predominantly at bedtime, with increases as needed to 200-300 mg/day for full antidepressant efficacy 2
• Maximum tolerated doses are 300-400 mg/day in elderly patients, while younger patients may tolerate up to 600 mg/day 3
• The once-daily formulation (TzCOAD/Oleptro) maintains effective blood levels for 24 hours while avoiding concentration peaks associated with side effects 4
• Bedtime-weighted dosing is supported by trazodone's 3-9 hour half-life and pharmacokinetics, providing improved sleep with less daytime drowsiness 2

Monitoring and Treatment Duration

• Patient status, therapeutic response, and adverse effects should be assessed regularly, beginning within 1-2 weeks of treatment initiation 5, 6
• Treatment should be modified if the patient does not have an adequate response within 6-8 weeks 5, 6
• After achieving remission, treatment should continue for at least 4-9 months for patients with a first episode of depression 5
• For patients with two or more episodes, longer maintenance treatment is strongly recommended to prevent recurrence 5, 6

Efficacy Profile

• Trazodone has demonstrated comparable antidepressant activity to other drug classes, including tricyclic antidepressants, SSRIs, and SNRIs 7
• Trazodone is particularly effective for patients with depression and comorbid insomnia, anxiety, or psychomotor agitation 4, 1
• As a serotonin receptor antagonist and reuptake inhibitor (SARI), trazodone may overcome tolerability issues associated with SSRIs such as insomnia, anxiety, and sexual dysfunction 7

Side Effect Considerations

• Most common adverse effects include drowsiness (somnolence/sedation), headache, dizziness, and dry mouth 7, 4
• Trazodone has minimal anticholinergic activity and low risk of weight gain and sexual dysfunction compared to other antidepressants 4, 1
• Less common but important side effects to monitor include:
  • Orthostatic hypotension (particularly in elderly patients or those with heart disease) 7, 4
  • QT interval prolongation and cardiac arrhythmias (rare) 7, 4
  • Priapism (rare but requires immediate medical attention) 7, 4

Treatment Approach Algorithm

1. Initial treatment: Start with 150 mg/day predominantly at bedtime 2
2. Dose adjustment: Increase gradually to 150-300 mg/day based on response and tolerability 1, 2
3. Monitoring: Assess therapeutic response and side effects within 1-2 weeks of initiation 5, 6
4. Response evaluation: If inadequate response after 6-8 weeks, consider treatment modification 5
5. Maintenance: Continue treatment for 4-9 months after remission for first episode; longer for recurrent depression 5, 6

Special Populations

• Elderly patients typically require lower maximum doses (300-400 mg/day) 3
• Patients with cardiovascular disease require careful monitoring for orthostatic hypotension 7, 4
• For patients with comorbid insomnia and depression, trazodone's sedative properties may be particularly beneficial 4, 1