What is the appropriate dose of Seroquel (quetiapine) for a patient with severe depression or bipolar disorder?

Quetiapine Dosing for Severe Depression and Bipolar Disorder

For bipolar depression, start quetiapine at 50 mg once daily at bedtime on Day 1, increase to 100 mg on Day 2,200 mg on Day 3, and reach the target dose of 300 mg/day by Day 4, which is both the recommended and maximum dose for this indication. 1

Dosing Algorithm by Indication

Bipolar Depression (Severe Depression in Bipolar Disorder)

• Day 1: 50 mg once daily at bedtime 1
• Day 2: 100 mg once daily at bedtime 1
• Day 3: 200 mg once daily at bedtime 1
• Day 4 and maintenance: 300 mg once daily at bedtime (this is both the recommended and maximum dose) 1
• Quetiapine 300 mg/day produces rapid and sustained improvements in depressive and anxiety symptoms in bipolar depression, with no additional benefit from 600 mg/day 2, 3

Bipolar Mania (Severe Mania)

• Day 1: 100 mg/day in divided doses (50 mg twice daily) 1
• Day 2: 200 mg/day in divided doses (100 mg twice daily) 1
• Day 3: 300 mg/day in divided doses (150 mg twice daily) 1
• Day 4: 400 mg/day in divided doses (200 mg twice daily) 1
• Days 5-6: Further adjustments up to 800 mg/day in increments of no greater than 200 mg/day 1
• Target dose: 400-800 mg/day in divided doses 1
• Maximum dose: 800 mg/day 1

Bipolar Maintenance Therapy (As Adjunct to Lithium or Valproate)

• Continue the same dose (400-800 mg/day in divided doses) on which the patient was stabilized during acute treatment 1
• Quetiapine maintenance therapy significantly reduces the risk of recurrence of any mood events and depression mood events for up to 52 weeks 2

Evidence for Efficacy

Bipolar Depression

• Quetiapine 300 mg/day produces significantly greater improvements than placebo in Montgomery-Asberg Depression Rating Scale scores, with significantly higher response and remission rates 2
• There are no differences in treatment outcomes between quetiapine 300 mg/day and 600 mg/day, making 300 mg/day the optimal dose 2
• Quetiapine is the only atypical antipsychotic approved in the US for monotherapy in both bipolar mania and depression 3
• Improvements in depressive and anxiety symptoms occur rapidly with quetiapine, along with improvements in health-related quality of life 3

Combination Therapy

• Quetiapine plus valproate is more effective than valproate alone for adolescent mania 4
• When added to mood stabilizers in patients with suboptimal response, quetiapine at mean doses of 203 mg/day (range 50-400 mg/day) produces significant improvements in Brief Psychiatric Rating Scale, Young Mania Rating Scale, and Hamilton Depression Rating Scale scores 5
• In clinical practice, quetiapine is associated with clinical improvement in >64% of all mood disorder patients at median doses of 200-400 mg/day 6

Special Population Dosing Adjustments

Elderly or Debilitated Patients

• Start at 50 mg/day and increase in increments of 50 mg/day depending on clinical response and tolerability 1
• Use a slower rate of dose titration and lower target doses in elderly patients and those with predisposition to hypotensive reactions 1

Hepatic Impairment

• Start at 25 mg/day and increase daily in increments of 25-50 mg/day to an effective dose 1

Drug Interactions

• With CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir): Reduce quetiapine dose to one-sixth of the original dose; when the inhibitor is discontinued, increase quetiapine dose by 6-fold 1
• With CYP3A4 inducers (phenytoin, carbamazepine, rifampin): Increase quetiapine dose up to 5-fold of the original dose for chronic treatment (>7-14 days); when the inducer is discontinued, reduce quetiapine to the original level within 7-14 days 1

Critical Safety Considerations

Tolerability Profile

• Most common adverse events are dry mouth, sedation, somnolence, dizziness, and constipation, typically mild to moderate in severity 2
• Quetiapine is more sedating than other atypical antipsychotics; beware of transient orthostasis 7
• Extrapyramidal symptoms occur at similar rates to placebo with no significant differences on objective measures 2
• Some patients experience clinically relevant weight gain, with mean weight gain of 10.9 lb (4.9 kg) in one study 2, 5
• Monitor for increases in blood glucose and lipid parameters, though clinical significance is uncertain 2

Monitoring Requirements

• Baseline metabolic assessment should include BMI, waist circumference, blood pressure, fasting glucose, and fasting lipid panel 4
• Follow-up monitoring should include BMI monthly for 3 months then quarterly, and blood pressure, glucose, and lipids at 3 months then yearly 4

Common Pitfalls to Avoid

• Do not exceed 300 mg/day for bipolar depression, as higher doses provide no additional benefit and increase adverse effects 1, 2
• Do not use quetiapine as monotherapy for unipolar depression without FDA approval—it is approved only as adjunctive treatment for major depressive disorder 2
• Quetiapine is not associated with increased risk of treatment-emergent mania in bipolar depression, making it safer than antidepressant monotherapy 3
• When restarting quetiapine after discontinuation for more than one week, follow the initial dosing schedule rather than resuming the previous dose 1
• For Alzheimer's disease with behavioral symptoms, use lower doses: initial 12.5 mg twice daily, maximum 200 mg twice daily 7