quetiapine

Quetiapine is an atypical antipsychotic in the dibenzothiazepine class. It is indicated for the treatment of schizophrenia, bipolar disorder (including manic, mixed, and depressive episodes), and as an adjunctive therapy in major depressive disorder. It is available in immediate- and extended-release forms.

Mechanism: Quetiapine exerts its therapeutic effects primarily as an antagonist at dopamine D2 receptors and serotonin 5-HT2A receptors, with additional antagonism at histamine H1 and alpha-1 adrenergic receptors. The drug is metabolized to norquetiapine, an active metabolite that contributes to antidepressant effects via norepinephrine reuptake inhibition and 5-HT1A partial agonism.

Pharmacokinetics: It is administered orally, with good absorption. It is metabolized by hepatic cytochrome P450 3A4 to norquetiapine, and both compounds are eliminated mainly in urine and feces. Typical half-lives differ: quetiapine about 6 hours; norquetiapine about 9–12 hours.

Adverse effects: Common adverse effects include sedation, dizziness, dry mouth, constipation, and weight gain. Metabolic effects such as increased glucose and lipids may occur. Extrapyramidal symptoms are less common than with first-generation antipsychotics. Orthostatic hypotension and sedation are notable; rare QT prolongation. Quetiapine carries a boxed warning about increased mortality in elderly patients with dementia-related psychosis.

Interactions and safety: Levels can be increased by strong CYP3A4 inhibitors (e.g., ketoconazole) and reduced by inducers (e.g., rifampin). Alcohol can enhance sedation. Cautions include elderly patients with dementia-related psychosis risk, potential precipitation of mania in bipolar disorder, and use during pregnancy (pregnancy category C).