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

Trazodone for Major Depressive Disorder: Treatment and Dosage Guidelines

For major depressive disorder, trazodone is recommended at an initial dosage of 150 mg/day, titrating to an effective therapeutic range of 150-300 mg/day for optimal antidepressant effect. 1

Dosing and Administration

• Trazodone is FDA-approved for the treatment of major depressive disorder in adults 2
• Initial dosage should be 25 mg per day, which can be gradually increased to the therapeutic range of 150-300 mg/day 3
• For antidepressant effects, doses of 150-300 mg/day are typically required, while lower doses are often used when trazodone is prescribed as an adjunct to other antidepressants 4
• Maximum dosage can reach 400 mg/day in divided doses, though this should be approached cautiously 3
• Trazodone should be taken shortly after a meal or light snack to improve absorption and minimize side effects 2

Monitoring and Treatment Timeline

• Begin assessment of patient status, therapeutic response, and adverse effects within 1-2 weeks of initiating therapy 3
• If adequate response is not achieved within 6-8 weeks, treatment modification is strongly recommended 3
• After achieving remission, continue treatment for 4-9 months to prevent relapse in patients with a first episode of major depressive disorder 3
• For patients with 2 or more previous depressive episodes, longer duration of therapy (years to lifelong) may be beneficial 3

Pharmacological Profile and Mechanism of Action

• Trazodone belongs to the SARI (Serotonin Antagonist and Reuptake Inhibitor) class of antidepressants 1
• It has a multimodal mechanism of action, acting as an antagonist of 5-HT2A and 5-HT2C serotonin receptors, alpha1 and alpha2 adrenergic receptors, and H1 histamine receptors 5
• At higher doses, trazodone blocks the SERT serotonin transporter, contributing to its antidepressant effect 5
• This complex pharmacodynamic profile explains its broad therapeutic spectrum and effectiveness for various depressive symptoms 4

Clinical Advantages and Considerations

• Trazodone is particularly effective for depression with comorbid insomnia, anxiety, and psychomotor agitation 4
• It has a rapid onset of action compared to some other antidepressants 1
• Trazodone has minimal anticholinergic effects and a lower risk of sexual dysfunction and weight gain compared to SSRIs 1
• It can be used both as monotherapy at 150-300 mg/day or in combination with other antidepressants at lower doses 1

Adverse Effects and Safety Considerations

• Common side effects include somnolence, headache, dizziness, and dry mouth 1
• Use with caution in patients with cardiovascular disease, as it may cause orthostatic hypotension, particularly in older adults 4
• Monitor for QT interval prolongation, especially when combined with other QT-prolonging medications 2
• Rare but serious side effects include priapism (painful erections lasting >6 hours), which requires immediate medical attention 2
• Trazodone may increase the risk of bleeding when used with antiplatelet agents or anticoagulants 2
• Screen patients for bipolar disorder before initiating treatment, as trazodone may trigger manic episodes in susceptible individuals 2

Special Populations

• In elderly patients, maximum tolerated doses are typically lower (300-400 mg/day) compared to younger adults (up to 600 mg/day) 6
• Elderly patients may be at higher risk for orthostatic hypotension and should be monitored closely 6
• Trazodone may be particularly useful for elderly patients with depression and insomnia 6

Formulations and Administration Tips

• Trazodone is available in immediate-release (IR) and once-a-day (OAD) formulations 7
• The OAD formulation maintains effective blood levels for 24 hours while avoiding concentration peaks associated with side effects 1
• Tablets should be swallowed whole or broken in half along the score line; do not chew or crush 2
• A gradual reduction in dosage rather than abrupt discontinuation is recommended to avoid withdrawal symptoms 2

By following these guidelines for dosing, monitoring, and addressing potential side effects, trazodone can be an effective option for treating major depressive disorder, particularly in patients with comorbid insomnia or anxiety.