Usage
Quetiapine is an atypical antipsychotic prescribed for:
- Schizophrenia: Treatment of acute psychotic episodes and maintenance therapy.
- Bipolar Disorder: Treatment of manic episodes (alone or with lithium or divalproex), depressive episodes, and maintenance therapy (with lithium or divalproex).
- Major Depressive Disorder (MDD): Adjunctive therapy to antidepressants (extended-release formulation only).
Pharmacological Classification: Atypical antipsychotic.
Mechanism of Action: Antagonist at multiple neurotransmitter receptors, including serotonin 5-HT2A, dopamine D2, histamine H1, and adrenergic α1 receptors. This combined action is thought to contribute to its therapeutic effects in various psychiatric conditions.
Alternate Names
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International Nonproprietary Name (INN): Quetiapine.
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Brand Names: Seroquel (immediate-release and extended-release), Quitide (various formulations).
How It Works
Pharmacodynamics: Quetiapine primarily acts by blocking serotonin 5-HT2A and dopamine D2 receptors. At lower doses, it shows higher affinity for serotonin receptors, which might explain its efficacy in treating depressive symptoms and anxiety. At higher doses, dopamine receptor antagonism becomes more prominent, contributing to its antipsychotic effects. It also has affinity for histamine H1 and adrenergic α1 receptors, which can lead to sedative and hypotensive effects, respectively.
Pharmacokinetics:
- Absorption: Rapidly absorbed after oral administration, reaching peak plasma concentrations in 1–2 hours (immediate-release) and approximately 6 hours (extended-release).
- Metabolism: Extensively metabolized in the liver, primarily by the cytochrome P450 (CYP) 3A4 enzyme. The major active metabolite is norquetiapine.
- Elimination: Excreted mainly in urine (73%) and feces (21%). The elimination half-life is about 7 hours for quetiapine and 12 hours for norquetiapine.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Quetiapine acts as an antagonist at serotonin 5-HT1A, 5-HT2A, 5-HT2C, dopamine D1, D2, histamine H1, and adrenergic α1 and α2 receptors. It does not significantly inhibit CYP enzymes, except for a slight inhibitory effect on CYP2D6.
Elimination Pathways: Primarily hepatic metabolism via CYP3A4, followed by renal and fecal excretion.
Dosage
Standard Dosage
Adults:
- Schizophrenia (IR): Initial 25 mg twice daily, increased by 25–50 mg two or three times daily up to 300–400 mg/day by day 4. Maintenance dose: 150-750 mg/day.
- Schizophrenia (XR): Initial 300 mg once daily, titrated up to 400–800 mg/day.
- Bipolar Mania (IR): Initial 100 mg twice daily, increasing by up to 100 mg twice daily to 400 mg/day by day 4, then by increments up to 200 mg/day, with a maximum of 800 mg/day by day 6.
- Bipolar Mania (XR): Initial 300 mg once daily, increasing to 600 mg/day on day 2. Maintenance dose: 400–800 mg/day.
- Bipolar Depression: 50 mg at bedtime on day 1, increased by 50–100 mg daily to 300 mg/day at bedtime.
- MDD (XR adjunct): 50 mg/day in the evening on days 1 and 2, increased to 150 mg/day on day 3. Usual dose: 150–300 mg/day.
Special Cases:
- Elderly: Lower starting doses and slower titration are recommended.
- Renal Impairment: No dose adjustment is typically necessary.
- Hepatic Impairment: Start with 25 mg/day and titrate cautiously.
- Comorbid Conditions: Careful monitoring is needed, especially in patients with cardiovascular disease or diabetes.
Clinical Use Cases
Quetiapine’s primary use is in managing psychosis and mood disorders. Evidence for its effectiveness in specific clinical settings like intubation, surgery, mechanical ventilation, and the ICU is limited. It might be used for agitation or delirium in these settings, but with caution.
Dosage Adjustments
Dosage adjustments are based on clinical response, tolerability, and patient-specific factors like age, hepatic impairment, and concomitant medications. Therapeutic drug monitoring may be useful.
Side Effects
Common Side Effects
- Somnolence, dizziness, dry mouth, constipation, weight gain, increased appetite, orthostatic hypotension, dyslipidemia, elevated liver enzymes.
Rare but Serious Side Effects
- Neuroleptic malignant syndrome (NMS), tardive dyskinesia, seizures, agranulocytosis, QT interval prolongation, severe hypersensitivity reactions, pancreatitis.
Long-Term Effects
- Weight gain, metabolic syndrome, movement disorders, cognitive impairment.
Adverse Drug Reactions (ADR)
- NMS, agranulocytosis, anaphylaxis, severe QT prolongation.
Contraindications
- Hypersensitivity to quetiapine.
- Coadministration with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin, clarithromycin).
Drug Interactions
- CYP3A4 Inhibitors: Increase quetiapine plasma levels, requiring dose reduction.
- CYP3A4 Inducers: Decrease quetiapine plasma levels, potentially reducing efficacy.
- CNS Depressants: Additive sedative effects.
- Antihypertensives: May enhance hypotensive effects.
- QT Prolonging Drugs: Increased risk of QT prolongation and torsades de pointes.
Pregnancy and Breastfeeding
- Pregnancy Category C: Use only if potential benefit outweighs risk.
- Breastfeeding: Quetiapine is excreted in breast milk; weigh risks and benefits.
Drug Profile Summary
- Mechanism of Action: Antagonist at multiple neurotransmitter receptors, including serotonin 5-HT2A, dopamine D2, histamine H1, and adrenergic α1 receptors.
- Side Effects: Somnolence, dizziness, dry mouth, weight gain, metabolic effects, extrapyramidal symptoms, NMS, tardive dyskinesia.
- Contraindications: Hypersensitivity, concomitant use of strong CYP3A4 inhibitors.
- Drug Interactions: CYP3A4 inhibitors and inducers, CNS depressants, QT prolonging drugs.
- Pregnancy & Breastfeeding: Use with caution; potential risks to fetus and neonate.
- Dosage: Varies depending on indication; adjust for age and hepatic impairment.
- Monitoring Parameters: Weight, blood pressure, fasting glucose, lipids, liver function tests, ECG (especially in high-risk patients).
Popular Combinations
Quetiapine is sometimes combined with lithium or divalproex for bipolar disorder maintenance therapy.
Precautions
- Monitor for metabolic effects, extrapyramidal symptoms, and QT prolongation.
- Caution in patients with cardiovascular disease, cerebrovascular disease, seizures, diabetes, hepatic or renal impairment.
- Avoid abrupt discontinuation.
FAQs
Q1: What is the recommended dosage for Quetiapine?
A: Depends on indication, formulation, and patient factors. Refer to detailed dosage guidelines above.
Q2: What are the common side effects of Quetiapine?
A: Somnolence, dizziness, dry mouth, constipation, weight gain, orthostatic hypotension.
Q3: How should Quetiapine be administered?
A: Orally, with or without food. Immediate-release is usually taken twice or three times daily, while extended-release is taken once daily.
Q4: What are the serious side effects of Quetiapine?
A: NMS, tardive dyskinesia, seizures, agranulocytosis, QT prolongation.
Q5: Can Quetiapine be used during pregnancy?
A: Pregnancy Category C; use cautiously if potential benefit outweighs risk.
Q6: How does Quetiapine interact with other drugs?
A: Significant interactions with CYP3A4 inhibitors and inducers, CNS depressants, and QT prolonging drugs.
Q7: What monitoring is required for patients on Quetiapine?
A: Weight, blood pressure, fasting glucose, lipids, liver function tests, ECG.
Q8: Is Quetiapine addictive?
A: Quetiapine does not typically cause physical dependence or addiction, but withdrawal symptoms can occur with abrupt discontinuation.
Q9: What are the symptoms of Quetiapine overdose?
A: Excessive sedation, coma, hypotension, tachycardia, delirium, seizures.
Q10: What is the role of Quetiapine in treating delirium?
A: Although not FDA-approved for this indication, quetiapine is sometimes used off-label to treat delirium, particularly in the ICU setting. However, its efficacy and safety in this context are not fully established.
