What is the recommended dosage of Trazodone (triazolopyridine antidepressant) for major depressive disorder?

Recommended Dosage of Trazodone for Major Depressive Disorder

For major depressive disorder, trazodone should be initiated at 150 mg/day in divided doses and may be increased gradually to 300-400 mg/day, with most patients responding within this dosage range. 1, 2

Initial Dosing and Titration

• Start with 150 mg/day in divided doses, with a major portion administered at bedtime to minimize daytime drowsiness 1
• Increase dosage gradually by 50 mg/day every 3-4 days based on clinical response and tolerability 1
• For outpatients, the maximum dose should not exceed 400 mg/day in divided doses 1
• For inpatients (more severely depressed patients), doses up to 600 mg/day may be administered in divided doses 1

Administration Recommendations

• Administer trazodone shortly after a meal or light snack to improve absorption and reduce side effects 1
• Consider a single nighttime dose or a dose weighted toward bedtime to leverage the sedative effects for patients with insomnia 3
• Tablets can be swallowed whole or broken along the score line if needed 1

Dosing Considerations for Special Populations

• Elderly patients typically tolerate maximum doses of 300-400 mg/day 4
• Lower starting doses may be appropriate for elderly or debilitated patients 4
• Consider dose reduction when co-administered with strong CYP3A4 inhibitors 1
• Consider dose increase when co-administered with strong CYP3A4 inducers 1

Therapeutic Plasma Concentration

• The recommended therapeutic plasma concentration range for trazodone is 650-1500 ng/mL 5
• This range is considered useful (level 3 recommendation) for monitoring treatment 5

Duration of Treatment

• A full therapeutic trial requires at least 4-8 weeks 5
• Dosage is typically increased using increments of initial dose every 5-7 days until therapeutic benefits or significant side effects become apparent 5
• After 9 months of treatment, consider dosage reduction to reassess the need for continued medication 5
• When discontinuing treatment, taper gradually over 10-14 days to limit withdrawal symptoms 5, 1

Efficacy and Side Effect Profile

• Trazodone at 150-300 mg/day is as effective as other antidepressants for treating major depressive disorder 2, 6
• Most common side effects include somnolence, headache, dizziness, and dry mouth 2
• Monitor for orthostatic hypotension, particularly in patients with cardiovascular disease or older adults 2
• Trazodone has minimal anticholinergic activity compared to tricyclic antidepressants 2, 6
• QT interval prolongation, cardiac arrhythmias, and priapism are rare but potential adverse effects 2

Clinical Pearls

• Trazodone may be particularly beneficial for patients with depression and comorbid insomnia due to its sedative properties 2, 6
• Studies comparing multiple daily dosing to single bedtime dosing have shown equal efficacy in relieving depression 3
• At treatment onset, a single nighttime dose may improve sleep with less daytime drowsiness 3
• The low risk of activating side effects and rapid onset of action make trazodone useful for many depressed patients 2
• Trazodone can be used as monotherapy at 150-300 mg/day or in combination with other antidepressants at lower doses 2

Remember that while the FDA-approved dosage range is 150-400 mg/day for outpatients, clinical response and tolerability should guide the final dosage determination within this range.