Ziprasidon

Ziprasidon is a second-generation (atypical) antipsychotic used to treat schizophrenia and bipolar I disorder. It is marketed under the brand name Geodon and by other names in different countries. The medication is available as oral capsules and as an intramuscular injection for acute agitation. When taken orally, it should be taken with food to improve absorption.

Mechanism of action and properties: Ziprasidon primarily blocks dopamine D2 and serotonin 5-HT2A receptors, and it has partial agonist activity at 5-HT1A receptors. It has relatively low activity at histamine H1 and muscarinic receptors, which is associated with a lower risk of weight gain and some cognitive effects but does not eliminate extrapyramidal symptoms. A notable safety concern is the potential to prolong the QT interval on the electrocardiogram, particularly in people with other risk factors.

Indications and use: It is approved for schizophrenia and for acute manic or mixed episodes in bipolar I disorder. It may be used as monotherapy or, in some settings, as short-term adjunctive therapy. The oral form is typically taken twice daily with meals.

Pharmacokinetics and dosing: Absorption is improved with meals; the drug has a relatively short half-life. It is metabolized mainly by aldehyde oxidase with minor involvement of CYP3A4. Typical dosing ranges from around 20 to 80 mg twice daily, adjusted for response and tolerability. The injectable form is used for acute agitation and is administered under medical supervision.

Safety and precautions: As with other antipsychotics, ziprasidone carries a boxed warning for increased mortality in elderly patients with dementia-related psychosis. QT prolongation risk requires caution in patients with electrolyte abnormalities or concurrent QT-prolonging medications. Common adverse effects include somnolence, dizziness, nausea, and modest weight changes.