Quetiapine Dosing for Acute Mania
For acute mania in bipolar I disorder, initiate quetiapine at 300 mg on day 1, increase to 600 mg on day 2, then use flexible dosing of 400-800 mg/day (typically 600-800 mg/day) from day 3 onward, administered in divided doses or once-daily if using extended-release formulation. 1
Rapid Titration Protocol
The most effective approach uses aggressive upward titration to achieve therapeutic doses quickly:
- Day 1: 200-300 mg 1, 2
- Day 2: 400-600 mg 1, 2
- Day 3: 600 mg 2
- Day 4 onward: 600-800 mg/day (target therapeutic range) 1, 2
This rapid escalation schedule has been specifically validated in acutely manic bipolar I patients and demonstrates symptom improvement starting at day 4-5 1, 2.
Target Therapeutic Dose
The recommended therapeutic dose for acute mania is 600-800 mg/day, with 600 mg/day being the minimum effective dose and 800 mg/day the typical maximum. 3, 1 Studies consistently show no additional benefit from 600 mg versus 800 mg doses, so starting at 600 mg after initial titration is reasonable 3.
Administration Considerations
- Extended-release formulation can be given once daily in the evening 1
- Immediate-release formulation should be divided into twice-daily dosing 4
- Monitor for orthostatic hypotension, especially during the first 3-4 days of titration 4, 5
- Sedation and somnolence are common but typically mild-to-moderate 1, 2
Critical Pitfall to Avoid
Do not use low doses (under 400 mg/day) for acute mania, as doses below 300 mg may paradoxically worsen manic symptoms through preferential 5HT2A receptor blockade over D2 antagonism, increasing dopamine concentrations. 6 This represents undertreatment and can lead to treatment failure or symptom exacerbation 6.
Expected Response Timeline
- First measurable improvement: Day 4-5 1, 2
- Response rate (≥50% YMRS reduction): 78% by day 21 2
- Remission rate: 70% by day 21 2
The rapid dose escalation protocol is both well-tolerated and effective, with no patients withdrawing due to adverse events during the critical first 7 days in validation studies 2.
Safety Monitoring
Monitor specifically for: