What is the recommended dosage and usage of Trazodone (antidepressant) for treating major depressive disorder and insomnia?

Trazodone Dosage and Usage for Major Depressive Disorder and Insomnia

Major Depressive Disorder (MDD)

For major depressive disorder, trazodone should be initiated at 150 mg/day in divided doses and may be gradually increased to 300 mg/day for full antidepressant efficacy, with a maximum of 400 mg/day for outpatients and 600 mg/day for inpatients. 1

Dosing Recommendations for MDD:

• Initial dose: 150 mg/day in divided doses 1
• Dose may be increased by 50 mg/day every 3-4 days based on clinical response and tolerance 1
• Effective antidepressant dose range: 200-300 mg/day 2
• Maximum dose: 400 mg/day for outpatients, 600 mg/day for inpatients 1
• Administration: Take shortly after a meal or light snack 1
• Once an adequate response has been achieved, dosage may be gradually reduced with subsequent adjustment depending on therapeutic response 1

Administration Strategy:

• Single nighttime dosing is as effective as multiple daily dosing for depression relief 2
• A bedtime-weighted dose improves sleep with less daytime drowsiness, especially during initial treatment 2
• Trazodone can be swallowed whole or administered as a half tablet by breaking along the score line 1

Insomnia

The American Academy of Sleep Medicine suggests that clinicians NOT use trazodone as a treatment for sleep onset or sleep maintenance insomnia in adults. 3, 4

Evidence Against Trazodone for Insomnia:

• The recommendation against trazodone for insomnia is based on trials of 50 mg doses 3
• Clinical trials showed only modest improvements in sleep parameters compared to placebo, with no improvement in subjective sleep quality 4
• The benefits of trazodone for sleep do not outweigh the potential harms according to the American Academy of Sleep Medicine guideline 3, 4
• The Department of Veterans Affairs/Department of Defense (VA/DOD) guidelines explicitly advise against trazodone for chronic insomnia disorder 4

Preferred Alternatives for Insomnia:

• First-line treatment: Cognitive behavioral therapy for insomnia (CBT-I) 4
• Pharmacological options recommended over trazodone include:
  • Suvorexant for sleep maintenance insomnia 3, 4
  • Eszopiclone for both sleep onset and maintenance insomnia 3, 4
  • Zolpidem for both sleep onset and maintenance insomnia 3, 4
  • Zaleplon for sleep onset insomnia 3, 4
  • Ramelteon for sleep onset insomnia 3, 4
  • Doxepin (3-6 mg) for sleep maintenance insomnia 3, 4

Special Considerations

Comorbid Depression and Insomnia:

• While not recommended for primary insomnia, trazodone may be considered when insomnia is a symptom of depression 4, 5
• Trazodone improves both sleep and depression in patients with MDD who have insomnia as a symptom 5
• Low-dose trazodone (50-100 mg) has been used off-label for insomnia in clinical practice, though this is not supported by current guidelines 6

Safety Considerations:

• Most common side effects: somnolence, headache, dizziness, and dry mouth 7
• Cardiovascular considerations:
  • Minimal effect on cardiac conduction 8
  • May cause orthostatic hypotension, especially in patients with cardiovascular disease or older adults 7
  • Rare risk of QT interval prolongation and cardiac arrhythmias 7
• Rare but serious side effect: priapism 4, 7
• Minimal anticholinergic activity 7
• Screen for bipolar disorder prior to starting trazodone 1
• Allow at least 14 days between discontinuation of an MAOI and initiation of trazodone, and vice versa 1
• Gradually reduce dosage rather than stopping abruptly when discontinuing treatment 1

Dose Adjustments:

• Consider reducing dose when co-administered with strong CYP3A4 inhibitors 1
• Consider increasing dose when co-administered with strong CYP3A4 inducers 1
• Lower doses (100-300 mg) are better tolerated and more effective in major depressives with significant cardiovascular disease 8

Practical Implementation

• For MDD: Start with 150 mg/day (can be given predominantly at bedtime) and increase as needed to 200-300 mg for full antidepressant efficacy 2
• If treating both depression and insomnia symptoms in MDD patients, the antidepressant dosage (150-300 mg/day) is typically sufficient to address both issues 7, 5
• Trazodone should not be used solely for primary insomnia treatment 3, 4