Introduction
Geodon (ziprasidone) is an atypical antipsychotic medication approved by the FDA in 2001. It belongs to the benzisothiazolyl piperazine class and is structurally distinct from other antipsychotic agents. Geodon is primarily used for the management of schizophrenia and bipolar disorder, offering a favorable metabolic profile compared to some other antipsychotics, though it carries specific cardiovascular considerations.
Mechanism of Action
Ziprasidone exerts its therapeutic effects through antagonism of dopamine D₂ and serotonin 5-HT₂A receptors. It has high affinity for these receptors, with approximately 5-fold greater affinity for 5-HT₂A than D₂ receptors. Additionally, ziprasidone acts as an antagonist at 5-HT₁D and 5-HT₂C receptors, and as an agonist at 5-HT₁A receptors. It moderately inhibits serotonin and norepinephrine reuptake, which may contribute to its efficacy in treating both positive and negative symptoms of schizophrenia and mood symptoms in bipolar disorder.
Indications
- Treatment of schizophrenia in adults
- Acute manic or mixed episodes associated with bipolar I disorder (as monotherapy or adjunct to lithium or valproate)
- Maintenance treatment of bipolar I disorder (as adjunct to lithium or valproate)
- Acute agitation in schizophrenic patients (intramuscular formulation)
Dosage and Administration
Oral administration:- Initial dose: 20 mg twice daily with food
- Titration: May increase to 60-80 mg twice daily based on response and tolerance
- Maximum recommended dose: 160 mg daily
- 10-20 mg every 2 hours as needed
- Maximum: 40 mg daily
- Hepatic impairment: Use with caution, no specific dose recommendation
- Renal impairment: No dose adjustment required
- Elderly: Consider lower starting doses
- Pediatric: Safety and effectiveness not established
Pharmacokinetics
Absorption: Well-absorbed with absolute bioavailability of approximately 60% when administered with food (fasting reduces absorption by up to 50%) Distribution: Extensive tissue distribution, protein binding >99% Metabolism: Primarily hepatic via aldehyde oxidase and CYP3A4 Elimination: Half-life ~7 hours, primarily excreted in feces (66%) with <1% excreted unchanged in urineContraindications
- Known hypersensitivity to ziprasidone
- History of QT prolongation or congenital long QT syndrome
- Recent acute myocardial infarction
- Uncompensated heart failure
- Concomitant use with other QT-prolonging drugs
- Significant hepatic impairment
Warnings and Precautions
Black Box Warning: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death- QT prolongation: Requires baseline ECG and periodic monitoring
- Neuroleptic malignant syndrome: Monitor for hyperpyrexia, muscle rigidity, altered mental status
- Tardive dyskinesia: May be irreversible
- Metabolic changes: Monitor glucose, lipids, and weight
- Seizures: Use cautiously in patients with seizure history
- Dysphagia: Esophageal dysmotility and aspiration risk
- Orthostatic hypotension: Particularly during initial titration
- Hyperprolactinemia: May occur
Drug Interactions
Major interactions:- QT-prolonging drugs (antiarrhythmics, macrolides, fluoroquinolones)
- Strong CYP3A4 inhibitors (ketoconazole, itraconazole): May increase ziprasidone levels
- CYP3A4 inducers (carbamazepine, rifampin): May decrease ziprasidone levels
- Antihypertensive agents: Additive hypotensive effects
- CNS depressants: Enhanced sedative effects
Adverse Effects
Common (≥10%):- Somnolence (14%)
- Headache (13%)
- Nausea (10%)
- Dizziness (8%)
- QT prolongation
- Neuroleptic malignant syndrome
- Tardive dyskinesia
- Seizures
- Diabetes mellitus and hyperglycemia
- Orthostatic hypotension
- Hyperprolactinemia
Monitoring Parameters
- Baseline and periodic ECGs (particularly with dose changes)
- Vital signs, especially during initial titration
- BMI, weight circumference
- Fasting blood glucose and lipid profile
- Extrapyramidal symptoms assessment
- Treatment response and psychiatric status
- Signs of hyperprolactinemia
- Electrolyte levels (particularly potassium and magnesium)
Patient Education
- Take with food (at least 500 calories) to ensure adequate absorption
- Do not abruptly discontinue medication
- Avoid alcohol consumption
- Rise slowly from sitting/lying position to prevent dizziness
- Report any unusual muscle movements, fever, or rigidity immediately
- Notify healthcare provider of any cardiac symptoms (palpitations, dizziness, syncope)
- Use caution when driving or operating machinery until effects are known
- Maintain regular follow-up appointments for monitoring
- Inform all healthcare providers of Geodon use
References
1. FDA Prescribing Information: Geodon (ziprasidone) hydrochloride. 2022 2. Stahl SM. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 4th ed. Cambridge University Press; 2013. 3. Kane JM, et al. Efficacy and safety of ziprasidone in the treatment of schizophrenia. Journal of Clinical Psychiatry. 2003;64(Suppl 19):36-49. 4. Keck PE, et al. Ziprasidone in the treatment of acute bipolar mania. American Journal of Psychiatry. 2003;160(4):741-748. 5. Miceli JJ, et al. The effects of ketoconazole on ziprasidone pharmacokinetics. British Journal of Clinical Pharmacology. 2000;49(S1):71S-76S. 6. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Schizophrenia. 3rd ed. 2021. 7. Marder SR, et al. Physical health monitoring of patients with schizophrenia. American Journal of Psychiatry. 2004;161(8):1334-1349.