Second-generation (atypical) antipsychotic
Antagonist at dopamine D₂ and serotonin 5-HT₂A receptors; also inhibits serotonin and norepinephrine reuptake, contributing to mood stabilization
Schizophrenia, acute manic or mixed episodes of bipolar I disorder
Psychosis in dementia, augmentation in major depressive disorder, acute agitation
Oral capsules, intramuscular injection for acute agitation
Oral dosing typically starts at 20 mg twice daily with food, titrated to 40–80 mg twice daily based on clinical response and tolerability
40–160 mg/day divided BID
Absorption requires concurrent food intake (≥500 calories) for adequate bioavailability; extensively metabolized hepatically primarily via aldehyde oxidase and CYP3A4; half-life approximately 7 hours
Somnolence, dizziness, akathisia, nausea
QT interval prolongation, which may increase risk of arrhythmias
Baseline and periodic ECG recommended especially in patients with cardiac risk factors or on other QT-prolonging medications; monitor for extrapyramidal symptoms and metabolic parameters although weight gain and metabolic changes are less common
Increased mortality in elderly patients with dementia-related psychosis
Ziprasidone may be preferred in patients at risk for weight gain or metabolic syndrome, including those with cognitive disorders. Use caution in patients with preexisting cardiac risk factors or who are taking other QT-prolonging drugs.