What is the recommended treatment and dosage for major depressive disorder using Desyrel (Trazodone)?

Trazodone (Desyrel) Treatment for Major Depressive Disorder

For major depressive disorder, trazodone should be initiated at 150 mg/day given predominantly at bedtime, and increased as needed to 200-300 mg/day for full antidepressant efficacy.

Dosing Recommendations

Trazodone is FDA-approved for the treatment of major depressive disorder (MDD) in adults 1. The recommended dosing strategy is:

• Starting dose: 150 mg/day, given predominantly at bedtime
• Therapeutic range: 200-300 mg/day for full antidepressant efficacy 2
• Maximum dose: 300-400 mg/day for elderly patients; up to 600 mg/day may be tolerated by younger patients 3
• Administration: Take shortly after a meal or light snack to minimize side effects 1

Treatment Algorithm

Initial Treatment Phase

1. Start with 150 mg given predominantly at bedtime
2. Assess response within 1-2 weeks of initiation (strong recommendation; moderate-quality evidence) 4
3. Titrate dose upward as needed to reach 200-300 mg/day for full antidepressant efficacy
4. Monitor for adequate response within 6-8 weeks of initiation (strong recommendation; moderate-quality evidence) 4

Response Evaluation

• If inadequate response after 6-8 weeks, modify treatment (strong recommendation; moderate-quality evidence) 4
• If satisfactory response, continue treatment for 4-9 months for first episode of MDD 4
• For patients with 2 or more episodes of depression, longer duration of therapy may be beneficial 4

Pharmacological Properties and Efficacy

Trazodone is a triazolopyridine serotonin receptor antagonist and reuptake inhibitor (SARI) with:

• Efficacy comparable to other available antidepressants 5
• Effectiveness for a range of depression symptoms, particularly insomnia 5
• Rapid onset of action, with significant reduction in Hamilton Depression Rating Scale scores within 1 week of starting treatment 6
• Low incidence of weight gain and sexual dysfunction, which may improve adherence to treatment 5

Side Effects and Monitoring

Common Side Effects

• Somnolence (most common)
• Headache (30% vs 19% in placebo)
• Dizziness
• Dry mouth (xerostomia) 5

Serious Adverse Effects (Rare)

• Priapism
• Orthostatic hypotension (especially in patients with cardiovascular disease or older adults)
• QT interval prolongation
• Cardiac arrhythmias 7, 5

Monitoring Recommendations

• Regular assessment of patient status, therapeutic response, and adverse effects beginning within 1-2 weeks of initiation 4
• Cardiovascular monitoring in patients with pre-existing cardiovascular disease
• Screen for bipolar disorder before initiating treatment 7
• Suicidality monitoring, especially in young adults within the first few months of treatment 1

Special Considerations

Elderly Patients

• Maximum tolerated doses are 300-400 mg/day 3
• Monitor closely for orthostatic hypotension 7

Drug Interactions

• Use caution with:
  • Monoamine oxidase inhibitors (MAOIs) - contraindicated within 2 weeks 1
  • Other serotonergic medications (risk of serotonin syndrome)
  • Strong CYP3A4 inhibitors or inducers (dose adjustment may be needed) 7

Discontinuation

• Gradually reduce dosage rather than stopping abruptly 7

Clinical Advantages

Trazodone offers several advantages for specific patient populations:

• Low anticholinergic activity compared to tricyclic antidepressants 8
• Beneficial for patients with comorbid insomnia 5
• Relatively safe in overdose compared to tricyclic antidepressants 3
• May be useful for elderly patients with anxiety and insomnia 3

The once-a-day formulation of trazodone has an improved tolerability profile compared to conventional formulations, which may enhance patient adherence 6.