Seroquel (Quetiapine): Indications, Dosing, and Safety Monitoring
FDA-Approved Indications
Quetiapine is FDA-approved for schizophrenia (adults and adolescents 13–17 years), acute bipolar mania (adults and children/adolescents 10–17 years as monotherapy or adjunct to lithium/valproate), bipolar depression (adults), and maintenance therapy for bipolar I disorder (adults as adjunct to lithium/valproate). 1
Schizophrenia
- Adults: Start 25 mg twice daily on Day 1, increase by 25–50 mg divided 2–3 times daily on Days 2–3 to reach 300–400 mg by Day 4, with a therapeutic range of 150–750 mg/day (maximum 750 mg/day) 1
- Adolescents (13–17 years): Start 25 mg twice daily on Day 1, increase to 100 mg total on Day 2,200 mg on Day 3,300 mg on Day 4, and 400 mg on Day 5, with a therapeutic range of 400–800 mg/day (maximum 800 mg/day) 1
Acute Bipolar Mania
- Adults (monotherapy or adjunct): Start with twice-daily dosing totaling 100 mg on Day 1, increase to 200 mg on Day 2,300 mg on Day 3, and 400 mg on Day 4, with further adjustments up to 800 mg/day by Day 6 in increments ≤200 mg/day; therapeutic range 400–800 mg/day 1
- Children/adolescents (10–17 years): Start 25 mg twice daily on Day 1, increase to 100 mg total on Day 2,200 mg on Day 3,300 mg on Day 4, and 400 mg on Day 5, with therapeutic range 400–600 mg/day (maximum 600 mg/day) 1
- Quetiapine plus valproate is more effective than valproate alone for adolescent mania 2
Bipolar Depression
- Adults: Administer once daily at bedtime, starting 50 mg on Day 1,100 mg on Day 2,200 mg on Day 3, and 300 mg on Day 4; therapeutic and maximum dose is 300 mg/day 1
Bipolar I Maintenance Therapy
- Adults: Administer 400–800 mg/day in divided doses as adjunct to lithium or valproate; patients generally continue on the same dose that achieved stabilization (maximum 800 mg/day) 1
Special Population Dosing
Elderly Patients
- Start quetiapine 50 mg/day and increase in 50 mg/day increments depending on clinical response and tolerability 1
- Use slower titration rates and lower target doses due to predisposition to hypotensive reactions 1
Hepatic Impairment
- Start 25 mg/day and increase daily in 25–50 mg/day increments to an effective dose based on clinical response 1
Drug Interactions
- CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir): Reduce quetiapine dose to one-sixth of original; when inhibitor is discontinued, increase quetiapine by sixfold 1
- CYP3A4 inducers (phenytoin, carbamazepine, rifampin): Increase quetiapine up to fivefold of original dose during chronic treatment (>7–14 days); when inducer is discontinued, reduce quetiapine to original level within 7–14 days 1
Clinical Efficacy and Evidence
Acute Mania
- Quetiapine monotherapy or combined with lithium/valproate is effective in reducing manic symptoms in adults and adolescents with acute bipolar mania 3, 4
- Response rates for lithium are 38–62% in acute mania, while valproate shows 53% response rates compared to 38% for lithium in children/adolescents with mania and mixed episodes 2
Bipolar Depression
- Quetiapine monotherapy is effective in reducing depressive symptoms in patients with bipolar depression 3, 4
Schizophrenia
- Quetiapine (up to 750 mg/day) is at least as effective as chlorpromazine (up to 750 mg/day) and haloperidol (up to 16 mg/day) in acute schizophrenia 5
- Efficacy is dose-related, with maximum effects at ≥250 mg/day 6
- Improvements with quetiapine (up to 800 mg/day) are similar to risperidone (up to 8 mg/day) or olanzapine (15 mg/day) 5
Safety Profile and Monitoring
Extrapyramidal Symptoms (EPS)
- Quetiapine is associated with placebo-level incidence of EPS across its entire dose range 3, 4, 5
- Significantly fewer EPS than haloperidol and may have advantages over chlorpromazine 5, 6
- Particularly suitable for EPS-vulnerable populations (elderly, adolescents, patients with Parkinson's disease or Alzheimer's disease) 7, 5
Prolactin
- Quetiapine does not elevate plasma prolactin levels compared to placebo at any dose; previously elevated levels may normalize 5, 6
Metabolic Effects
- Quetiapine has minimal short-term effects on body weight and a favorable long-term weight profile 5
- For atypical antipsychotics generally, baseline monitoring should include BMI, waist circumference, blood pressure, fasting glucose, and fasting lipid panel, with follow-up BMI monthly for 3 months then quarterly, and blood pressure/glucose/lipids at 3 months then yearly 2
Common Adverse Events
- Headache (19.4% vs. 17.5% placebo), somnolence (17.5% vs. 10.7% placebo), and dizziness (9.6% vs. 4.4% placebo) are most common 6
- Postural hypotension, tachycardia, constipation, dry mouth, dyspepsia, and transient liver enzyme elevations occur in ≥5% of patients 6
- Weight gain of approximately 2.1 kg in short-term trials 6
Thyroid and Hepatic Effects
- Small dose-related decreases in total and free thyroxine; effects usually reverse with treatment cessation 6
- Asymptomatic, generally transient elevations in hepatic transaminases (particularly ALT) 6
Cardiovascular
- No statistically significant differences from placebo in ECG parameters including QT, QTc, and PR intervals 6
Older Adults with Dementia
- Quetiapine is recommended for control of problematic delusions, hallucinations, severe psychomotor agitation, and combativeness in Alzheimer's disease 8
- Initial dose: 12.5 mg twice daily; maximum: 200 mg twice daily; more sedating and requires monitoring for transient orthostasis 8
Reinitiation and Switching
Reinitiation After Discontinuation
- If off quetiapine >1 week: Follow initial dosing schedule 1
- If off quetiapine <1 week: Gradual dose escalation may not be required; maintenance dose may be reinitiated 1
Switching from Other Antipsychotics
- Immediate discontinuation of previous antipsychotic may be acceptable for some patients; gradual discontinuation may be appropriate for others 1
- Minimize period of overlapping antipsychotic administration 1
- When switching from depot antipsychotics, initiate quetiapine in place of next scheduled injection 1
- Re-evaluate need for continuing EPS medication periodically 1
Maintenance Therapy Considerations
- Patients should be periodically reassessed to determine need for maintenance treatment and appropriate dose 1
- Maintenance therapy should continue for at least 12–24 months after mood stabilization 2
- Withdrawal of maintenance lithium therapy is associated with increased relapse risk, especially within 6 months; >90% of noncompliant adolescents relapsed versus 37.5% of compliant patients 2
Common Pitfalls to Avoid
- Underdosing: Quetiapine requires adequate dosing (≥250 mg/day for schizophrenia, 400–800 mg/day for mania) to achieve maximum efficacy 6, 1
- Inadequate trial duration: Systematic 6–8 week trials at adequate doses are required before concluding ineffectiveness 2
- Premature discontinuation: Inadequate maintenance therapy duration leads to high relapse rates 2
- Ignoring drug interactions: Failure to adjust dose with CYP3A4 inhibitors/inducers can lead to toxicity or treatment failure 1
- Neglecting metabolic monitoring: Failure to monitor for metabolic side effects, particularly weight gain, is a common oversight with atypical antipsychotics 2