What is the recommended titration schedule for quetiapine (Seroquel)?

Quetiapine Titration Schedule

For adults with schizophrenia or bipolar mania, start quetiapine at 25 mg twice daily on Day 1, increase to 50 mg twice daily on Day 2, then 100 mg twice daily on Day 3, reaching 150-200 mg twice daily by Day 4, with a target dose of 300-400 mg/day by Days 4-5. 1

Standard Titration for Adults

Schizophrenia

• Day 1: 25 mg twice daily 1
• Day 2: Increase by 25-50 mg in divided doses (2-3 times daily) 1
• Day 3: Continue increments of 25-50 mg 1
• Day 4: Target range of 300-400 mg/day 1
• Further adjustments: Can increase in increments of 25-50 mg twice daily at intervals of no less than 2 days 1
• Effective dose range: 150-750 mg/day 1
• Maximum dose: 750 mg/day 1

Bipolar Mania (Adults)

• Day 1: 100 mg/day in divided doses (twice daily) 1
• Day 2: 200 mg/day in divided doses 1
• Day 3: 300 mg/day in divided doses 1
• Day 4: 400 mg/day in divided doses 1
• Further adjustments: Up to 800 mg/day by Day 6 in increments no greater than 200 mg/day 1
• Target dose range: 400-800 mg/day 1
• Maximum dose: 800 mg/day 1

Bipolar Depression

• Administer once daily at bedtime 1
• Day 1: 50 mg 1
• Day 2: 100 mg 1
• Day 3: 200 mg 1
• Day 4: 300 mg 1
• Target and maximum dose: 300 mg/day 1

Adolescent Dosing (13-17 years for Schizophrenia; 10-17 years for Bipolar Mania)

Schizophrenia (Ages 13-17)

• Day 1: 25 mg twice daily 1
• Day 2: 100 mg/day in divided doses 1
• Day 3: 200 mg/day in divided doses 1
• Day 4: 300 mg/day in divided doses 1
• Day 5: 400 mg/day in divided doses 1
• Further adjustments: Increments no greater than 100 mg/day 1
• Target dose range: 400-800 mg/day 1
• Maximum dose: 800 mg/day 1

Bipolar Mania (Ages 10-17)

• Day 1: 25 mg twice daily 1
• Day 2: 100 mg/day in divided doses 1
• Day 3: 200 mg/day in divided doses 1
• Day 4: 300 mg/day in divided doses 1
• Day 5: 400 mg/day in divided doses 1
• Target dose range: 400-600 mg/day 1
• Maximum dose: 600 mg/day 1

Special Population Modifications

Elderly Patients

Start at 50 mg/day and increase in increments of 50 mg/day based on clinical response and tolerability. 1 The American Academy of Family Physicians recommends an even more conservative approach with 12.5 mg twice daily initially, with a maximum of 200 mg twice daily. 2 Elderly patients are at higher risk for transient orthostatic hypotension and sedation, requiring slower dose escalation and careful monitoring. 2

Hepatic Impairment

• Start at 25 mg/day 1
• Increase daily in increments of 25-50 mg/day to an effective dose based on clinical response and tolerability 1

Drug Interactions Requiring Dose Adjustment

With CYP3A4 Inhibitors (ketoconazole, itraconazole, ritonavir, nefazodone):

• Reduce quetiapine dose to one-sixth of the original dose 1
• When the inhibitor is discontinued, increase quetiapine by 6-fold 1

With CYP3A4 Inducers (phenytoin, carbamazepine, rifampin, St. John's wort):

• Increase quetiapine dose up to 5-fold of the original dose when used chronically (>7-14 days) 1
• Titrate based on clinical response and tolerability 1
• When the inducer is discontinued, reduce quetiapine to the original level within 7-14 days 1

Rapid Titration in Acute Settings

Research evidence supports that quetiapine can be safely titrated to 400 mg/day in as little as 2-3 days in acutely ill hospitalized patients, rather than the standard 5-day schedule. 3 A pilot study demonstrated similar safety and tolerability when escalating to 400 mg/day over 5,3, or 2 days, with only 3 of 69 patients withdrawing due to adverse events (agitation). 3 Case series have also shown that rapid dose escalation to higher doses (up to 1600 mg/day) can be well tolerated in acute schizophrenia and mania. 4

However, the FDA-approved labeling remains the standard of care for most clinical situations, and rapid titration should be reserved for hospitalized patients under close monitoring. 1

Reinitiation After Discontinuation

• If off quetiapine for more than one week: Follow the initial dosing schedule 1
• If off quetiapine for less than one week: Gradual dose escalation may not be required; the maintenance dose may be reinitiated 1

Key Clinical Considerations

Dosing frequency: While the FDA label recommends twice or three times daily dosing for most indications, research supports that twice daily administration is as effective as three times daily for a total dose of 450 mg/day. 5 Bipolar depression is the exception, administered once daily at bedtime. 1

Dose-response relationship: Clinical efficacy is dose-related, with maximum effects occurring at dosages ≥250 mg/day. 5 Patients not responding to lower doses should be titrated upward within the approved range. 6

Common pitfalls: Avoid stopping titration prematurely at subtherapeutic doses. The target therapeutic range for schizophrenia is 300-450 mg/day, and many patients require 400-800 mg/day for optimal response. 1, 5