Quetiapine Titration for Depression
For major depressive disorder, start quetiapine XR at 50 mg once daily at bedtime, increase to 150 mg on Day 2, then to 300 mg on Day 3, with the effective dose being 300 mg/day. 1
Standard Titration Schedule
The FDA-approved titration for bipolar depression differs from the emerging evidence for unipolar depression:
Bipolar Depression (FDA-Approved)
- Day 1: 50 mg once daily at bedtime
- Day 2: 100 mg once daily at bedtime
- Day 3: 200 mg once daily at bedtime
- Day 4: 300 mg once daily at bedtime (target dose)
- Maximum dose: 300 mg/day 1
Major Depressive Disorder (Off-Label, Based on Research)
- Starting dose: 50 mg once daily
- Titration: Can advance to 150 mg or 300 mg/day based on tolerability
- Effective doses: 50 mg, 150 mg, or 300 mg/day, with 150 mg/day showing the most consistently positive results across efficacy measures 2
- Improvement in depressive symptoms can be observed as early as Day 4 of treatment 2
Dosing Considerations
The 150 mg/day dose appears optimal for unipolar depression, as it provided more consistently positive secondary efficacy results compared to both 50 mg/day and 300 mg/day versus placebo. 2 Higher doses (600 mg/day) used in bipolar mania are not necessary or recommended for depression. 3, 4
Special Populations
Elderly or debilitated patients require slower titration:
- Start at 50 mg/day
- Increase in increments of 50 mg/day based on clinical response and tolerability
- Use caution with dose escalation 1
Hepatically impaired patients need even more conservative dosing:
- Start at 25 mg/day
- Increase daily in increments of 25-50 mg/day to reach effective dose 1
Monitoring During Titration
The most common adverse effects during titration are dry mouth, sedation, somnolence, dizziness, and headache. 2 These are typically mild to moderate in severity. 3
Watch for:
- Orthostatic hypotension, particularly with the immediate-release formulation 5
- Weight gain and metabolic changes (glucose, lipids) 3
- Sedation, which may require dosing adjustment or slower titration 2
Extrapyramidal symptoms are uncommon at antidepressant doses and occur at similar rates to placebo. 3
Clinical Pearls
- Quetiapine XR (extended-release) is preferred over immediate-release for depression due to once-daily dosing and potentially better tolerability 2
- Response can be seen within 4 days of starting treatment, well before reaching the target dose 2
- For augmentation of SSRIs in treatment-resistant depression with comorbid anxiety, quetiapine XR 50-300 mg/day (flexible dosing) has demonstrated efficacy 6
- The antidepressant mechanism likely involves the active metabolite norquetiapine's norepinephrine reuptake inhibition, distinct from its antipsychotic effects 3