Trazodone Dosing
For depression, start trazodone at 150 mg/day in divided doses and increase by 50 mg every 3-4 days up to 400 mg/day for outpatients (600 mg/day for inpatients), but for insomnia, trazodone is not recommended as the American Academy of Sleep Medicine advises against its use based on insufficient efficacy. 1, 2
Depression Dosing (FDA-Approved Indication)
Initial dosing:
- Start at 150 mg/day in divided doses 1
- Initiate at low dose and increase gradually based on clinical response and tolerability 1
- If drowsiness occurs, administer the major portion of the daily dose at bedtime or reduce the dose 1
Dose titration:
- Increase by 50 mg/day every 3 to 4 days 1
- Outpatients: maximum 400 mg/day in divided doses 1
- Inpatients (more severely depressed): up to 600 mg/day in divided doses 1
Alternative dosing strategy:
- Single nighttime dosing at 150 mg is equally effective as divided doses, with less daytime drowsiness initially 3
- Increase to 200-300 mg as needed for full antidepressant efficacy, given predominantly at bedtime 3
- This approach leverages trazodone's 3-9 hour half-life and improves sleep without tolerance 3
Maintenance and discontinuation:
- Once adequate response achieved, gradually reduce dosage 1
- Taper slowly rather than stopping abruptly to avoid withdrawal symptoms 1
Administration Instructions
- Take shortly after a meal or light snack to optimize absorption 1
- Tablets can be swallowed whole or broken along the score line 1
- Screen for bipolar disorder history before initiating treatment 1
Drug Interactions Requiring Dose Adjustment
With strong CYP3A4 inhibitors:
- Consider reducing trazodone dose based on tolerability 1
With strong CYP3A4 inducers:
- Consider increasing trazodone dose based on therapeutic response 1
With MAOIs:
- Allow at least 14 days between discontinuing an MAOI and starting trazodone 1
- Allow at least 14 days after stopping trazodone before starting an MAOI 1
Insomnia: Why Trazodone Is Not Recommended
The American Academy of Sleep Medicine explicitly recommends against trazodone for insomnia based on weak evidence showing only modest improvements without meaningful subjective sleep quality benefits at 50 mg doses. 2, 4
Key problems with trazodone for insomnia:
- Clinical trials showed no improvement in subjective sleep quality despite modest objective sleep parameter changes 2
- Potential harms outweigh benefits according to current guidelines 2
- Adverse effects include daytime drowsiness, dizziness, psychomotor impairment, and rare but serious risks like priapism 2
- The VA/DOD guidelines explicitly advise against its use for chronic insomnia 2
Preferred alternatives for insomnia:
- First-line: Cognitive behavioral therapy for insomnia (CBT-I) 2, 4
- Second-line pharmacologic options:
Special Clinical Scenarios
When trazodone may be considered for insomnia:
- As a third-line agent after benzodiazepine receptor agonists and ramelteon have failed 2
- When comorbid depression is present (though low doses used for insomnia are inadequate for treating major depression) 5, 2
- In combination with a full-dose antidepressant for a patient with depression and insomnia 5
Dosing when used off-label for insomnia (despite guideline recommendations against):
- Typical doses are 25-50 mg at bedtime, which are below therapeutic antidepressant range 2
- Note that even 50 mg showed insufficient efficacy in clinical trials 2
Important Safety Considerations
- Most common adverse effects: somnolence, headache, dizziness, dry mouth 6
- Serious but rare risks: orthostatic hypotension (especially in elderly or cardiovascular disease), QT prolongation, cardiac arrhythmias, priapism 6
- Minimal anticholinergic activity compared to tricyclic antidepressants 6
- Safe in overdose when taken alone 7
- Caution in elderly patients—consider dose reduction 5
- Avoid in pregnancy/nursing 5
- Caution with compromised respiratory function, hepatic or heart failure 5