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

Trazodone Dosage and Treatment Protocol for Major Depressive Disorder

For patients with major depressive disorder, trazodone should be initiated at 150 mg/day in divided doses, with gradual increases of 50 mg every 3-4 days as needed, to a maximum of 400 mg/day for outpatients or 600 mg/day for inpatients. 1

Initial Dosing and Titration

• Start with 150 mg/day in divided doses 1
• Increase by 50 mg/day every 3-4 days based on clinical response and tolerability 1
• Maximum recommended dose is 400 mg/day for outpatients and 600 mg/day for inpatients 1
• For elderly patients, lower doses are typically better tolerated, with maximum tolerated doses of 300-400 mg/day 2

Administration Guidelines

• Administer shortly after a meal or light snack to improve absorption and reduce side effects 1
• Tablets can be swallowed whole or broken along the score line for half doses 1
• Consider administering a major portion of the daily dose at bedtime if drowsiness occurs 1
• Single nighttime dosing (rather than multiple daily doses) may improve sleep with less daytime drowsiness while maintaining equal antidepressant efficacy 3

Treatment Duration

• Acute phase treatment: 6-12 weeks 4
• Continue treatment for 4-9 months after satisfactory response for first episode of MDD 4
• For patients with 2 or more episodes, longer duration of therapy (years to lifelong) may be beneficial 4
• When discontinuing, gradually reduce the dosage rather than stopping abruptly to minimize withdrawal symptoms 1

Monitoring and Assessment

• Begin monitoring therapeutic response and adverse effects within 1-2 weeks of initiating therapy 4
• Assess for emergence of agitation, irritability, or unusual changes in behavior, especially during the first 1-2 months of treatment when suicide risk is higher 4
• Modify treatment if adequate response is not achieved within 6-8 weeks 4
• Target plasma concentration range for trazodone is 650-1500 ng/mL 4

Efficacy and Clinical Considerations

• Trazodone is effective for a range of depression symptoms, particularly beneficial for patients with comorbid insomnia 5
• At therapeutic doses of 150-300 mg/day, trazodone shows comparable efficacy to other antidepressants 5, 6
• Early improvement in depressive symptoms may be observed within 1 week of starting treatment at 150 mg/day 7
• Low incidence of weight gain and sexual dysfunction may improve treatment adherence 5

Potential Side Effects and Precautions

• Most common adverse effects: somnolence, headache, dizziness, and dry mouth 5
• Use with caution in patients with premature ventricular contractions 4
• Monitor for orthostatic hypotension, especially in patients with cardiovascular disease or older adults 5
• Rare but serious side effects include QT interval prolongation, cardiac arrhythmias, and priapism 5
• Screen for bipolar disorder before initiating treatment 1
• Allow at least 14 days between discontinuing MAOIs and starting trazodone, and vice versa 1

Special Populations

• For elderly or debilitated patients, consider lower starting doses and slower titration 2
• Consider dose reduction when co-administering with strong CYP3A4 inhibitors 1
• Consider dose increase when co-administering with strong CYP3A4 inducers 1

Trazodone's unique pharmacological profile makes it particularly useful for patients with depression accompanied by insomnia, anxiety, or psychomotor agitation, while avoiding common side effects associated with other antidepressants such as sexual dysfunction and weight gain 6.