Clinical Overview
Ziprasidone is an atypical antipsychotic indicated for schizophrenia and bipolar disorder. It has a unique receptor profile with significant serotonin and norepinephrine reuptake inhibition in addition to dopamine and serotonin receptor antagonism. It has a favorable metabolic profile with minimal weight gain but requires food for absorption and carries QT prolongation risk.
Primary Clinical Applications
Ziprasidone is indicated for schizophrenia and acute manic or mixed episodes of bipolar I disorder. It may be particularly suitable for patients concerned about weight gain and metabolic effects, as it typically causes minimal weight gain and has low diabetes risk compared to other atypical antipsychotics.
Mechanism and Clinical Benefits
Ziprasidone antagonizes dopamine D2 and serotonin 5-HT2A receptors while also inhibiting serotonin and norepinephrine reuptake. This unique combination may provide antidepressant effects in addition to antipsychotic activity. The medication also has activity at 5-HT1A, 5-HT1D, and alpha-1 adrenergic receptors.
Clinical Considerations
Ziprasidone must be taken with food (≥500 calories) to achieve adequate absorption – without food, bioavailability is reduced by 50%. It can cause QT prolongation, requiring ECG monitoring in patients with cardiac risk factors. The medication has a favorable metabolic profile but may cause more QT prolongation than other atypicals.
Prescribing Information
Dosing & Administration
Schizophrenia – Adults:
- Initial: 20 mg twice daily with food
- Titration: May increase on day 2 to 40 mg twice daily
- Range: 40-80 mg twice daily
- Maximum: 80 mg twice daily (160 mg/day)
Bipolar I Disorder – Manic/Mixed Episodes:
- Initial: 40 mg twice daily with food
- Day 2: Increase to 60-80 mg twice daily
- Range: 40-80 mg twice daily
- Maximum: 80 mg twice daily
Acute Agitation (IM injection):
- Dose: 10-20 mg IM
- Maximum: 40 mg daily, 10 mg every 2 hours or 20 mg every 4 hours
Administration:
- Critical: Take with food containing ≥500 calories
- Divide daily dose into twice daily dosing
- IM injection for acute use only (max 3 consecutive days)
Indications
- Treatment of schizophrenia in adults
- Acute treatment of manic or mixed episodes associated with bipolar I disorder
- Acute agitation in schizophrenic patients (IM injection)
Contraindications
- Known hypersensitivity to ziprasidone
- Recent acute myocardial infarction
- Uncompensated heart failure
- History of QT prolongation
- Concurrent use with other QT-prolonging drugs
Warnings & Precautions
- Boxed Warning: Increased mortality in elderly patients with dementia-related psychosis
- QT prolongation: Baseline and periodic ECG monitoring recommended
- Neuroleptic malignant syndrome: Rare but serious risk
- Tardive dyskinesia: Risk with long-term use
- Hyperglycemia: Monitor glucose in diabetic patients
- Orthostatic hypotension: Monitor blood pressure
Drug Interactions
- QT-prolonging drugs: Contraindicated or use extreme caution
- CYP3A4 inhibitors: May increase ziprasidone levels
- Carbamazepine: Decreases ziprasidone levels significantly
- Antiarrhythmics: Additive QT effects
Adverse Reactions
Common (≥5%):
- Somnolence, respiratory tract infection, dizziness
- Extrapyramidal symptoms, nausea, rash
Metabolic advantages:
- Minimal weight gain, low diabetes risk
- Minimal effects on lipids
Serious:
- QT prolongation, neuroleptic malignant syndrome
Special Populations
- Cardiac disease: ECG monitoring required, may be contraindicated
- Hepatic/Renal Impairment: No dose adjustment typically needed
- Elderly: Increased mortality risk in dementia-related psychosis
- Food requirement: Must take with ≥500 calories for adequate absorption
- Pregnancy: Category C – use only if benefits outweigh risks
Medical Disclaimer: This information is for educational purposes only and is not intended as medical advice. Always consult with qualified healthcare professionals before making any treatment decisions. Individual patient circumstances may vary significantly.
