Ziprasidone
Geodon
Second-Generation AntipsychoticGeneric availableTDM data
The mechanism of action of ziprasidone in the treatment of the listed indications could be mediated through a combination of dopamine type 2 (D 2 ) and serotonin type 2 (5HT 2 ) antagonism.
Compare Ziprasidone →FDA-Approved Indications
- Schizophrenia (adults)
- Acute mania/mixed episodes in Bipolar I — monotherapy (adults)
- Bipolar I maintenance — adjunct to lithium/valproate (adults)
- Acute agitation in schizophrenia (IM, adults)
Common Off-Label Uses
- Agitation in dementia
- Bipolar depression
- Treatment-resistant depression (adjunct)
What Sets This Drug Apart
- Highest QTc prolongation among SGAs (Huhn MD 9.70 ms, Leucht MD 7.73 ms — both class top); contraindicated in patients with QT prolongation history, recent MI, or uncompensated heart failure
- Most favorable weight and lipid profile among SGAs: Pillinger weight P-score 0.10, LDL P-score 0.12 (both lower-quartile); negative weight point estimates in NMAs
- Absorption increases ~2-fold with food (FDA label); must take with meals, though no specific calorie threshold is stated in the label
- Two-thirds of metabolism is non-CYP (aldehyde oxidase reduction) — CYP3A4 inhibitors increase AUC only ~35%, less drug-interaction sensitivity than most SGAs
- Often underdosed in clinical practice (<120 mg/day); inadequate response may reflect subtherapeutic dosing rather than drug failure
- Low prolactin effect and sexual dysfunction risk (roughly one-third that of risperidone/paliperidone)
Boxed Warning
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Elderly patients with dementia-related psychosis treated wi