What are the recommended dosing regimens for quetiapine (Seroquel) in adults with schizophrenia, acute manic or mixed bipolar episodes, bipolar depression or as adjunctive therapy for major depressive disorder, and in elderly patients with dementia‑related psychosis, including dose adjustments for hepatic impairment?

Quetiapine Dosing Recommendations

Schizophrenia in Adults

For acute treatment of schizophrenia in adults, start quetiapine at 25 mg twice daily on Day 1, rapidly titrate to 300-400 mg/day by Day 4, with a target dose of 150-750 mg/day divided into 2-3 doses. 1

• Initial titration schedule: Day 1: 25 mg twice daily; Days 2-3: increase by 25-50 mg increments divided 2-3 times daily to reach 300-400 mg by Day 4 1
• Maintenance dosing: 400-800 mg/day, with maximum efficacy typically achieved at ≥250 mg/day and doses ≥600 mg/day showing consistent effectiveness 1, 2, 3
• Maximum dose: 750 mg/day, though robust controlled data suggest standard dosing (150-450 mg/day) is appropriate for most patients 1, 4
• Further adjustments can be made in 25-50 mg twice daily increments at intervals of at least 2 days based on response 1

Schizophrenia in Adolescents (13-17 years)

Adolescents require more aggressive titration, starting at 25 mg twice daily on Day 1 and reaching 400 mg/day by Day 5, with a target range of 400-800 mg/day. 1

• Titration schedule: Day 1: 25 mg twice daily; Day 2: 100 mg total; Day 3: 200 mg total; Day 4: 300 mg total; Day 5: 400 mg total 1
• Maintenance: 400-800 mg/day divided into 2-3 doses, with adjustments in increments no greater than 100 mg/day 1
• Maximum dose: 800 mg/day 1

Bipolar Mania in Adults

For acute bipolar mania (monotherapy or adjunct to lithium/divalproex), initiate at 100 mg/day total (divided twice daily) and rapidly escalate to 400 mg by Day 4, with target dosing of 400-800 mg/day. 1

• Titration: Day 1: 100 mg total; Day 2: 200 mg total; Day 3: 300 mg total; Day 4: 400 mg total 1
• Further increases up to 800 mg/day by Day 6 should be in increments no greater than 200 mg/day 1
• Effective dose range: 600 mg/day consistently demonstrates efficacy 2
• Maximum dose: 800 mg/day 1

Bipolar Mania in Children/Adolescents (10-17 years)

Pediatric bipolar mania requires starting at 25 mg twice daily and titrating to 400 mg by Day 5, with a target of 400-600 mg/day. 1

• Titration: Day 1: 25 mg twice daily; Day 2: 100 mg total; Day 3: 200 mg total; Day 4: 300 mg total; Day 5: 400 mg total 1
• Adjustments in increments no greater than 100 mg/day within 400-600 mg/day range 1
• Maximum dose: 600 mg/day (lower than adult maximum) 1

Bipolar Depression in Adults

For bipolar depression, administer quetiapine once daily at bedtime, starting at 50 mg on Day 1 and reaching the target dose of 300 mg/day by Day 4. 1

• Titration: Day 1: 50 mg; Day 2: 100 mg; Day 3: 200 mg; Day 4: 300 mg 1
• Target and maximum dose: 300 mg/day at bedtime 1
• Studies consistently demonstrate effectiveness at 150-300 mg/day for unipolar depression and 300-600 mg/day for bipolar depression 2

Adjunctive Therapy for Major Depressive Disorder

When used as adjunct therapy for MDD, follow the bipolar depression dosing regimen of 50-300 mg/day administered once daily at bedtime. 1, 2

Elderly Patients

Elderly patients require dramatically reduced starting doses of 50 mg/day with slower titration in 50 mg/day increments, due to 20-30% higher drug exposure and up to 50% lower clearance compared to younger adults. 1, 3

• Starting dose: 50 mg/day (not the standard 25 mg twice daily) 1
• Titration: Increase in 50 mg/day increments based on clinical response and tolerability 1
• Target dose: Generally lower than standard adult dosing, likely in the range of 25 mg starting dose with careful escalation 3
• Elderly patients demonstrate 20-30% higher maximum plasma concentrations and area under the curve values 3

Elderly Patients with Dementia-Related Psychosis

For elderly patients with dementia-related psychosis, initiate at 25 mg/day and titrate cautiously in 25-50 mg increments to an effective dose, with median doses around 137.5 mg/day proving effective in long-term studies. 3, 5

• Long-term data (52 weeks) in elderly patients with psychotic disorders showed median total daily dose of 137.5 mg was well-tolerated 5
• Common adverse events include somnolence (31%), dizziness (17%), and postural hypotension (15%), though these rarely necessitate withdrawal 5
• Critical safety consideration: Quetiapine is less likely to cause extrapyramidal symptoms compared to typical antipsychotics, with EPS-related events occurring in only 13% of elderly patients 6, 5

Hepatic Impairment

Patients with hepatic impairment must start at 25 mg/day with daily increases of 25-50 mg to reach an effective dose, as oral clearance is reduced by approximately 25% in hepatic cirrhosis. 1, 7

• Starting dose: 25 mg/day 1
• Titration: Increase by 25 mg/day increments 1
• Dose escalation should be performed with caution due to inter-subject variability in clearance among cirrhotic patients 7
• Single-dose pharmacokinetic studies showed no clinically significant differences, but the recommended starting dose remains 25 mg with cautious escalation 7

Renal Impairment

No dosage adjustment is necessary for renal impairment, as pharmacokinetic studies show no clinically significant differences compared to healthy controls, though standard elderly dosing precautions apply if the patient is also elderly. 7

• Quetiapine had no effect on endogenous creatinine clearance in renally impaired subjects 7
• Standard dosing can be used unless the patient has other risk factors (e.g., advanced age) 7

Drug Interactions: CYP3A4 Inhibitors

When co-administered with potent CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, nefazodone), reduce quetiapine dose to one-sixth of the original dose. 1

• This dramatic reduction is necessary because quetiapine is extensively metabolized via CYP3A4 sulphoxidation 1, 3
• Conversely, CYP3A4 inducers may require dose increases 3

Common Pitfalls to Avoid

• Do not use standard adult doses in elderly patients: This significantly increases risk of adverse outcomes including falls, orthostatic hypotension, and oversedation 1, 5
• Do not exceed 750-800 mg/day without clear justification: Robust controlled data indicate standard dosing (150-450 mg/day) is appropriate for most schizophrenia patients, and higher doses lack strong evidence of superior efficacy 4
• Do not combine with high-dose benzodiazepines in elderly patients: Fatalities have been documented with benzodiazepine combinations, particularly with high-dose olanzapine (a related atypical antipsychotic), suggesting caution with all atypical antipsychotics in this population 6
• Monitor for metabolic effects even at low doses: Weight gain (approximately 2.1 kg) and triglyceride elevations can occur across all dose ranges and psychiatric indications 2, 3