Trazodone Dosage and Usage for Major Depressive Disorder and Insomnia
Recommended Dosage for Major Depressive Disorder
For major depressive disorder, trazodone should be initiated at 150 mg/day in divided doses and can be gradually increased to 300 mg/day for optimal antidepressant efficacy, with a maximum of 400 mg/day for outpatients and 600 mg/day for inpatients. 1
The dosing regimen should follow these guidelines:
- Start with 150 mg/day in divided doses
- Increase by 50 mg/day every 3-4 days based on clinical response and tolerance
- Maximum dose: 400 mg/day for outpatients, 600 mg/day for inpatients
- Once adequate response is achieved, dosage may be gradually reduced with subsequent adjustments based on therapeutic response
- Administration should be shortly after a meal or light snack 1
Administration Options
- Can be swallowed whole or administered as a half tablet by breaking along the score line
- For improved tolerability, a major portion of the daily dose may be administered at bedtime 1
- Single nighttime dosing has shown equal efficacy to multiple daily dosing in relieving depression while improving sleep with less daytime drowsiness 2
Usage for Insomnia
While trazodone is not FDA-approved as a first-line treatment for insomnia in non-depressed patients, it is commonly prescribed off-label for this purpose:
- Low-dose trazodone (typically 25-100 mg) is often used off-label for insomnia 3
- For patients with MDD and comorbid insomnia, trazodone is particularly beneficial as it addresses both conditions 4, 5
- The American Geriatrics Society does not recommend trazodone as first-line therapy for insomnia in elderly patients due to side effects including sedation, dizziness, and psychomotor impairment 6
Special Considerations
Drug Interactions
- Allow at least 14 days between discontinuing MAOIs and starting trazodone, and vice versa 1
- Consider dose reduction when co-administered with strong CYP3A4 inhibitors
- Consider dose increase when co-administered with strong CYP3A4 inducers 1
Screening and Monitoring
- Screen for bipolar disorder prior to initiating treatment 1
- Gradually reduce dosage when discontinuing to prevent withdrawal symptoms 1
- Monitor for common side effects: somnolence, headache, dizziness, and dry mouth 7
Advantages of Trazodone
- Low risk of anticholinergic side effects, weight gain, and sexual dysfunction 7, 5
- Effective for a broad range of depressive symptoms, particularly insomnia 5
- Improved sleep without tolerance development or REM rebound on discontinuation 2
- Once-daily formulation maintains effective blood levels for 24 hours while avoiding concentration peaks associated with side effects 7
Safety Concerns
- May cause orthostatic hypotension, especially in patients with cardiovascular disease or older adults
- Rare but serious side effects include QT interval prolongation, cardiac arrhythmias, and priapism 7
- Side effects are dose-dependent, with drowsiness being the most common 3
Clinical Pitfalls to Avoid
- Using high doses (≥100 mg) for insomnia treatment in non-depressed patients
- Failing to taper when discontinuing treatment
- Not accounting for potential drug interactions with CYP3A4 inhibitors or inducers
- Overlooking the need to screen for bipolar disorder before initiating treatment