Quetiapine (Seroquel): Recommended Use and Dosing
Primary Indications
Quetiapine is FDA-approved for schizophrenia, acute bipolar mania (as monotherapy or adjunct to lithium/divalproex), and bipolar depression, with specific dosing protocols that differ substantially by indication. 1
Schizophrenia in Adults
- Start with 25 mg twice daily on Day 1 1
- Increase by 25-50 mg increments divided 2-3 times daily on Days 2-3 to reach 300-400 mg by Day 4 1
- Target dose: 150-750 mg/day in divided doses 1
- Maximum dose: 750 mg/day 1
- Further adjustments should be made in increments of 25-50 mg twice daily, with intervals of at least 2 days between changes 1
Schizophrenia in Adolescents (13-17 years)
- Day 1: 25 mg twice daily 1
- Day 2: 100 mg total (divided twice daily) 1
- Day 3: 200 mg total (divided twice daily) 1
- Day 4: 300 mg total (divided twice daily) 1
- Day 5: 400 mg total (divided twice daily) 1
- Target dose: 400-800 mg/day, with adjustments no greater than 100 mg/day 1
- Maximum dose: 800 mg/day 1
- May be administered three times daily based on response and tolerability 1
Acute Bipolar Mania in Adults
- Day 1: 100 mg total (divided twice daily) 1
- Day 2: 200 mg total (divided twice daily) 1
- Day 3: 300 mg total (divided twice daily) 1
- Day 4: 400 mg total (divided twice daily) 1
- Further increases up to 800 mg/day by Day 6 should be in increments no greater than 200 mg/day 1
- Target dose: 400-800 mg/day 1
- Maximum dose: 800 mg/day 1
- Can be used as monotherapy or adjunct to lithium or divalproex 1
Acute Bipolar Mania in Children/Adolescents (10-17 years)
- Day 1: 25 mg twice daily 1
- Day 2: 100 mg total (divided twice daily) 1
- Day 3: 200 mg total (divided twice daily) 1
- Day 4: 300 mg total (divided twice daily) 1
- Day 5: 400 mg total (divided twice daily) 1
- Target dose: 400-600 mg/day 1
- Maximum dose: 600 mg/day 1
- Adjustments should be no greater than 100 mg/day 1
Bipolar Depression in Adults
- 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
Bipolar Maintenance Therapy
- Continue 400-800 mg/day in divided doses as adjunct to lithium or divalproex 1
- Generally maintain patients on the same dose they were stabilized on during acute treatment 1
- Quetiapine plus valproate is more effective than valproate alone for adolescent mania 2
Special Population Dosing
Elderly Patients
- Start at 50 mg/day 1
- Increase in 50 mg/day increments based on clinical response and tolerability 1
- Use slower titration rates and lower target doses due to predisposition to hypotensive reactions 1
- Quetiapine may be particularly useful in elderly patients with psychotic symptoms and neurological disorders like Parkinson's or Alzheimer's disease due to its tolerability profile 3
Hepatically Impaired Patients
Clinical Efficacy Profile
Symptom Coverage
- Effective against both positive symptoms (hallucinations, delusions) and negative symptoms (emotional withdrawal, apathy) of schizophrenia 4, 3
- Improves cognitive function compared to haloperidol 4
- Reduces depressive symptoms and hostility/aggression 4
- At least as effective as chlorpromazine and haloperidol in acute schizophrenia 4
- Similar efficacy to risperidone and olanzapine in head-to-head comparisons 4
Maintenance Treatment
- Efficacy maintained for at least 52 weeks in open-label follow-up studies 4
- Patients should be periodically reassessed to determine need for continued maintenance treatment 1
Tolerability and Safety Profile
Favorable Characteristics
- Placebo-level incidence of extrapyramidal symptoms (EPS) across entire dose range 4, 5
- Does not elevate plasma prolactin levels compared to placebo, and previously elevated levels may normalize 4
- Minimal short-term effects on body weight with favorable long-term weight profile 4
- More favorable EPS profile than risperidone 4
Common Adverse Effects
- Dizziness, hypotension, somnolence, and weight gain are the most common side effects 6
- Changes in ECG, thyroid hormone, and hepatic enzyme levels appear clinically insignificant 6
Drug Interactions
- Metabolized by CYP 3A4 system 6
- Interacts with phenytoin, carbamazepine, barbiturates, rifampin, and glucocorticoids, which may require dosage adjustment 6
- No dose adjustment needed when co-administered with fluoxetine, imipramine, haloperidol, or risperidone 6
- May enhance effects of antihypertensive agents 6
- May antagonize effects of levodopa and dopamine 6
Critical Clinical Considerations
Administration
- Can be taken with or without food 1
- Optimal treatment typically requires 2-3 divided oral doses daily for most indications 6
- Bipolar depression is the exception, requiring once-daily bedtime dosing 1
Monitoring Requirements
- For adolescents on atypical antipsychotics including quetiapine: monitor BMI monthly for 3 months then quarterly, and blood pressure, fasting glucose, and lipids after 3 months then yearly 2
- Regular assessment of treatment response and tolerability is essential 1
Common Pitfalls to Avoid
- Do not use rapid titration schedules - follow the specific day-by-day titration protocols to minimize adverse effects 1
- Do not exceed maximum daily doses - 750 mg/day for schizophrenia in adults, 800 mg/day for adolescent schizophrenia and adult bipolar mania, 600 mg/day for pediatric bipolar mania, and 300 mg/day for bipolar depression 1
- Do not use as monotherapy for bipolar depression in adolescents - always combine with mood stabilizer when treating bipolar depression 2
- Be aware of potential for abuse and dependence, particularly in patients with substance use disorders or in correctional settings, where quetiapine may be used for its anxiolytic and sedative effects 7
Vulnerable Populations
- Quetiapine has a low risk for EPS in vulnerable patient groups including the elderly, adolescents, and patients with organic brain disorders 4
- High level of patient acceptability and satisfaction reported in preliminary studies 4
- Patients on long-term treatment report high compliance, good satisfaction, and improvements in quality of life 3