QUTI 200

Indications

• Schizophrenia
• Bipolar disorder
• Major depressive disorder (as an adjunct therapy)

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: Refer to the relevant clinical guidelines or BNF for specific dosing information.

Mechanism of action

Quetiapine acts primarily as an antagonist at various neurotransmitter receptors in the brain, particularly the dopamine D2 and serotonin 5-HT2A receptors. This dual action helps to balance dopamine and serotonin levels, which may be dysregulated in patients with schizophrenia and mood disorders. It also exhibits activity at adrenergic receptors, contributing to its sedative effects.

Pharmacodynamics

Quetiapine's efficacy in treating schizophrenia and bipolar disorder is linked to its ability to modulate dopaminergic and serotonergic neurotransmission. By blocking D2 receptors, it reduces dopaminergic hyperactivity, which is associated with the positive symptoms of schizophrenia. The blockade of 5-HT2A receptors may help alleviate negative symptoms and improve mood stability. The drug's sedative properties are related to its antagonistic action on histamine H1 receptors.

Pharmacokinetics

Quetiapine is well-absorbed following oral administration, with peak plasma concentrations reached within 1.5 hours. It undergoes extensive hepatic metabolism, primarily via the cytochrome P450 enzyme CYP3A4, producing several metabolites, some of which may have pharmacological activity. The elimination half-life ranges from 5 to 7 hours, with a steady-state achieved in approximately 2 days. The drug is predominantly excreted in urine, with a minor portion eliminated via feces.

Contra-indications

• Hypersensitivity to quetiapine or any of its components
• Severe hepatic impairment
• Concurrent use of strong CYP3A4 inhibitors

Adverse effects

• Sedation
• Dizziness
• Dry mouth
• Constipation
• Weight gain
• Hyperglycemia
• Extrapyramidal symptoms
• Neuroleptic malignant syndrome
• Tardive dyskinesia

Interactions

• CYP3A4 inhibitors may increase quetiapine levels
• CYP3A4 inducers may decrease quetiapine levels
• Concurrent use with other CNS depressants may enhance sedative effects
• Antihypertensive agents may have additive effects on blood pressure

Precautions

• Monitor for signs of metabolic syndrome
• Use with caution in patients with a history of seizures
• Consider risks in patients with cardiovascular disease
• Assess for potential for increased mortality in elderly patients with dementia-related psychosis

Pregnancy

Quetiapine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data on use during pregnancy.

Breast-feeding

Quetiapine is excreted in breast milk. Caution should be exercised when administered to a nursing mother.

Storage

Store at room temperature, away from heat and moisture. Keep out of reach of children.

Formulations

• Tablets
• Extended-release tablets