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

Trazodone Dosing for Major Depressive Disorder

For major depressive disorder, start trazodone at 150 mg/day (preferably as a single dose at bedtime) and titrate to 200-300 mg/day for full antidepressant efficacy. 1, 2, 3

Initial Dosing Strategy

• Begin with 150 mg/day as the starting antidepressant dose, administered predominantly or entirely at bedtime 2, 3
• Lower starting doses (25-50 mg/day) are insufficient for antidepressant effect and should only be used when trazodone is prescribed as an adjunct for insomnia with another primary antidepressant 2
• Single nighttime dosing is superior to divided doses at treatment onset, producing better sleep with less daytime drowsiness 3

Titration and Maintenance

• Increase to 200-300 mg/day as needed for full antidepressant response 1, 2, 3
• Maximum tolerated doses are 300-400 mg/day in elderly patients, while younger patients may tolerate up to 600 mg/day 4
• The once-daily formulation maintains effective blood levels for 24 hours while avoiding concentration peaks associated with side effects 1

Timeline for Response Assessment

• Expect early improvement within 1 week of starting treatment, particularly for sleep disturbance and depressive symptoms 5
• Trazodone demonstrates statistically significant reduction in depression rating scales within 7 days compared to placebo or venlafaxine 5
• This represents a faster onset of action than many SSRIs 6
• Continue treatment for 4-9 months after satisfactory response in first-episode depression 6

Special Populations and Considerations

Elderly Patients

• Start at approximately 50% of standard adult doses due to increased risk of adverse drug reactions 7
• Maximum doses typically 300-400 mg/day in this population 4
• Monitor closely for orthostatic hypotension, which occurs more frequently in older adults and those with cardiovascular disease 1, 4

Patients with Specific Symptom Profiles

• Particularly effective when depression presents with insomnia, anxiety, or psychomotor agitation 1, 2
• Useful in patients with depression and anorexia or weight loss, as trazodone does not cause weight gain 6, 1
• Appropriate for patients who cannot tolerate sexual dysfunction or activating side effects of SSRIs 1, 2

Monitoring Requirements

• Assess therapeutic response and adverse effects within 1-2 weeks of initiation 6
• Monitor for orthostatic hypotension, especially during dose escalation and in at-risk patients 1, 4
• Watch for QT interval prolongation and cardiac arrhythmias in patients with cardiovascular disease 1
• Be aware of rare but serious risk of priapism (requires patient education) 1, 4

Common Adverse Effects

• Somnolence/sedation (most common, often beneficial for insomnia) 1, 2
• Headache and dizziness 1
• Dry mouth (xerostomia) 1
• Minimal anticholinergic effects compared to tricyclic antidepressants 1, 2
• Low risk of weight gain and sexual dysfunction 1, 2

Critical Safety Considerations

• Use with caution in patients with premature ventricular contractions or cardiovascular disease 7
• Relatively safe in overdose compared to tricyclic antidepressants 4
• Monitor for orthostatic hypotension, particularly in elderly patients and those with pre-existing cardiovascular conditions 1, 4
• Educate male patients about priapism risk and need for immediate medical attention if erection persists beyond 4 hours 1

Treatment Modification

• If inadequate response after 6-8 weeks at therapeutic doses (200-300 mg/day), consider switching to an SSRI or SNRI, or adding another antidepressant with different mechanism 6
• For recurrent depression (2+ episodes), plan for longer duration of maintenance therapy beyond the initial 4-9 months 6