Trazodone Dosing for Major Depressive Disorder
For major depressive disorder, start trazodone at 150 mg daily (predominantly at bedtime) and titrate to 200-300 mg/day for full antidepressant efficacy. 1
Initial Dosing Strategy
- Begin with 150 mg given predominantly at bedtime, which provides both antidepressant effect and addresses sleep disturbances common in depression 1
- The bedtime-weighted dosing strategy is supported by trazodone's 3-9 hour half-life and produces better sleep with less daytime drowsiness at treatment onset 1
- Single nighttime dosing shows equal efficacy to multiple daily dosing for relieving depression 1
Therapeutic Dose Range
- The appropriate antidepressant dose range is 150-300 mg/day for major depressive disorder 2
- Maximum recommended dose is 400 mg/day in divided doses 3
- Doses of 75-600 mg daily have been used in clinical practice, though higher doses are less common 4
Titration Protocol
- Increase from the initial 150 mg dose to 200-300 mg as needed to achieve full antidepressant response 1
- Dose increases should occur every 5-7 days using increments of the initial dose until therapeutic benefits or significant side effects appear 3
- Begin assessing therapeutic response and adverse effects within 1-2 weeks of treatment initiation 5
Response Timeline and Treatment Duration
- If inadequate response occurs within 6-8 weeks, treatment modification is strongly recommended 5
- A full therapeutic trial requires at least 4-8 weeks 3
- Continue treatment for 4-9 months after satisfactory response in first-episode depression 5
- For patients with 2 or more depressive episodes, longer duration therapy is beneficial 5
Special Populations
Elderly Patients
- Start at approximately 50% of the adult starting dose (around 75 mg) in older adults 3
- Initial dosage of 25 mg/day with maximum of 200-400 mg/day in divided doses has been recommended for geriatric populations 3
- Geriatric patients respond similarly to single nighttime dosing as younger adults 1
- Use with caution in patients with premature ventricular contractions 3
Formulation-Specific Considerations
Prolonged-Release (T-RP)
- Particularly useful for mild-to-moderate depression with prominent sleep disturbance and/or moderate-to-severe anxiety 6
- Provides higher peak blood concentrations beneficial during specific periods (falling asleep, periods of increased anxiety-agitation) 6
Once-Daily (T-OAD)
- Indicated for moderate-to-severe depression with mild-to-moderate sleep/anxiety disorders 6
- Can start at 150 mg (already potentially effective dose) and increase to 300 mg 6
- Particularly helpful for late insomnia (early morning awakening) 6
- Single evening dosing potentially improves treatment adherence 6
Clinical Advantages
- Trazodone is particularly suitable for depression accompanied by insomnia or weight loss due to its sleep-promoting and appetite-stimulating properties 5
- Effective for patients with depression and comorbid insomnia, anxiety, or psychomotor agitation 2
- Low risk of anticholinergic side effects, weight gain, and sexual dysfunction compared to tricyclics and SSRIs 2, 7
- Safe in overdose with no deaths reported when trazodone alone is ingested 7
Common Side Effects to Monitor
- Sedation/somnolence (most common) 1, 5
- Dizziness and orthostatic hypotension 4
- Gastrointestinal dysfunction 4
- Dry mouth 5, 4
- These effects typically diminish with continued administration 1
Important Caveats
- The 150-300 mg antidepressant dose range is higher than doses used for augmentation strategies (e.g., when adding trazodone to an SSRI for insomnia) 2
- Trazodone is metabolized primarily by CYP2D6 and CYP3A4, requiring dose adjustment when co-administered with drugs affecting these isoenzymes 4
- After 9 months of treatment, consider dose reduction to reassess the need for continued medication 3