Quetiapine Dosing for Depression
For bipolar depression, start quetiapine at 50 mg once daily at bedtime on Day 1, increase to 100 mg on Day 2,200 mg on Day 3, and reach the target dose of 300 mg/day on Day 4. 1
FDA-Approved Indication and Dosing
Quetiapine is FDA-approved specifically for bipolar depression, not unipolar major depressive disorder as monotherapy. 1
Standard Titration Schedule for Bipolar Depression
The FDA label provides a clear 4-day titration protocol administered once daily at bedtime: 1
- Day 1: 50 mg
- Day 2: 100 mg
- Day 3: 200 mg
- Day 4: 300 mg (target and maximum dose)
The maximum dose for bipolar depression is 300 mg/day, which is notably lower than dosing for schizophrenia (up to 750 mg/day) or bipolar mania (up to 800 mg/day). 1
Clinical Evidence Supporting 300 mg Dosing
Multiple randomized controlled trials demonstrate that quetiapine 300 mg/day is effective for bipolar depression, with no additional benefit from higher doses. 2, 3, 4 Studies comparing 300 mg/day versus 600 mg/day showed no differences in treatment outcomes, supporting 300 mg as the optimal dose. 2
Efficacy is evident early, with significant improvements in depressive symptoms observed by Day 4 of treatment. 5
Special Population Adjustments
Elderly or Debilitated Patients
Start at 50 mg/day and increase in 50 mg/day increments based on clinical response and tolerability. 1 The American Academy of Family Physicians emphasizes monitoring for orthostatic hypotension, particularly with immediate-release formulations during titration. 6
Hepatic Impairment
Start at 25 mg/day and increase daily in 25-50 mg/day increments to reach an effective dose. 1
Drug Interactions
- With CYP3A4 inhibitors (ketoconazole, ritonavir, nefazodone): Reduce quetiapine dose to one-sixth of the original dose. 1
- With CYP3A4 inducers (phenytoin, carbamazepine, rifampin): Increase quetiapine dose up to 5-fold of the original dose when used chronically (>7-14 days). 1
Off-Label Use in Unipolar Depression
While quetiapine extended-release has been studied as augmentation for major depressive disorder at doses of 50-300 mg/day, this remains an off-label use. 5, 7 A recent trial showed quetiapine XR augmentation (50-300 mg/day flexible dosing) improved depression and anxiety symptoms in MDD with comorbid anxiety disorders, though it was generally well-tolerated with mostly minor adverse effects. 7
Safety Monitoring
Monitor for orthostatic hypotension during titration, especially in elderly patients. 6 Common adverse effects include dry mouth, sedation, somnolence, dizziness, and constipation. 2, 5 Weight gain and metabolic changes (glucose, lipids) can occur and warrant monitoring, though the clinical significance varies. 2
Quetiapine is not associated with increased risk of treatment-emergent mania in bipolar depression. 3, 4
Reinitiation After Discontinuation
If quetiapine has been discontinued for more than one week, restart using the initial dosing schedule rather than resuming at the previous maintenance dose. 1