What is the recommended use and dosage of quetiapine (Seroquel) for treating psychiatric disorders?

Quetiapine (Seroquel) for Psychiatric Disorders

Quetiapine is a second-generation antipsychotic approved for schizophrenia, bipolar mania, and bipolar depression, with dosing ranging from 300-800 mg/day for psychotic disorders and 300 mg/day for bipolar depression, administered in divided doses or once daily depending on the formulation and indication. 1

Primary Indications and Evidence Base

Schizophrenia

• Second-generation antipsychotics like quetiapine may be considered as alternatives to first-line agents (haloperidol or chlorpromazine) if availability can be assured and cost is not a constraint 2
• For adults with schizophrenia: Start 25 mg twice daily on Day 1, increase by 25-50 mg increments to reach 300-400 mg by Day 4, with a recommended dose range of 150-750 mg/day (maximum 750 mg/day) 1
• For adolescents (13-17 years): Start 25 mg twice daily on Day 1, titrate to 400-800 mg/day by Day 5 (maximum 800 mg/day) 1
• Quetiapine demonstrates efficacy comparable to typical antipsychotics for positive symptoms without causing extrapyramidal symptoms or prolactin elevation 3

Bipolar Disorder

Bipolar Mania:

• For adults: Start with twice-daily dosing totaling 100 mg on Day 1, increase to 400 mg by Day 4, with recommended dose of 400-800 mg/day (maximum 800 mg/day) 1
• For children and adolescents (10-17 years): Start 25 mg twice daily, titrate to 400-600 mg/day by Day 5 (maximum 600 mg/day) 1
• Second-generation antipsychotics are recommended as alternatives to haloperidol if cost and availability permit 2

Bipolar Depression:

• Administer once daily at bedtime: 50 mg on Day 1,100 mg on Day 2,200 mg on Day 3, and 300 mg on Day 4 (recommended and maximum dose: 300 mg/day) 1
• Both 300 mg and 600 mg doses demonstrated significantly greater improvements than placebo in Montgomery-Asberg Depression Rating Scale scores, with no difference between the two doses 4
• Quetiapine monotherapy is effective for both bipolar I and bipolar II depression, including patients with rapid cycling history 5

Key Pharmacological Properties

• Quetiapine has high central anticholinergic activity among antipsychotics, along with clozapine and olanzapine 2
• The antidepressant mechanism may involve 5-HT2A receptor antagonism, 5-HT1A partial agonism, or noradrenaline reuptake inhibition by the metabolite norquetiapine 4
• Metabolized via CYP3A4 with an elimination half-life of approximately 6 hours 3

Special Populations

Elderly Patients:

• Start at 50 mg/day and increase in 50 mg/day increments based on clinical response and tolerability 1
• Use lower doses due to predisposition to hypotensive reactions 1

Hepatic Impairment:

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

Delirium in Cancer Patients:

• Start 25 mg (immediate release) orally stat, give every 12 hours if scheduled dosing required 2
• Reduce dose in older patients and those with hepatic impairment 2
• Quetiapine is sedating and less likely to cause extrapyramidal symptoms than other atypical antipsychotics 2
• May cause orthostatic hypotension and dizziness; oral route only 2

Adverse Effects and Monitoring

Common Side Effects:

• Most frequent: dry mouth, sedation, somnolence, dizziness, constipation, and increased appetite 4
• Weight gain occurs more frequently than with placebo 4
• Extrapyramidal symptoms occur at similar rates to placebo with no significant differences on objective measures 4
• May cause orthostatic hypotension, particularly with initial dosing 2

Metabolic Monitoring:

• Before starting: BMI, waist circumference, blood pressure, HbA1c, glucose, lipids, prolactin, liver function tests, urea and electrolytes, full blood count, and electrocardiogram 2
• Fasting glucose re-check at 4 weeks 2
• BMI, waist circumference, and blood pressure weekly for 6 weeks 2
• Repeat all measures at 3 months and annually thereafter 2
• Some patients experience clinically relevant increases in blood glucose or lipid parameters, though clinical significance remains uncertain 4

Maintenance Therapy

Schizophrenia and Bipolar I Disorder:

• Continue at 400-800 mg/day for maintenance; patients generally remain on the dose they were stabilized on during acute treatment 1
• Antipsychotic treatment should continue for at least 12 months after beginning of remission 2
• Quetiapine responders who continued therapy had significantly reduced risk of recurrence of any mood events and depressive mood events for up to 52 weeks 4

Bipolar Disorder Maintenance:

• Maintenance treatment should continue for at least 2 years after the last episode 2
• In one trial, quetiapine maintenance for up to 104 weeks was more efficacious than placebo or lithium in prolonging time to recurrence of any mood event 4

Drug Interactions

• Quetiapine interacts with phenytoin, carbamazepine, barbiturates, rifampin, and glucocorticoids; coadministration may require dosage adjustment 3
• No dose adjustment needed when coadministered with fluoxetine, imipramine, haloperidol, or risperidone 3
• May enhance effects of antihypertensive agents and antagonize effects of levodopa and dopamine 3

Clinical Considerations

• Quetiapine can be taken with or without food 1
• The extended-release formulation allows once-daily dosing with similar bioavailability but prolonged plasma levels compared to immediate-release 6
• Direct switching from immediate-release to the same dose of extended-release does not reveal loss of efficacy or tolerability issues 6
• For akathisia management, consider switching to quetiapine or olanzapine as alternatives 2