What is ziprasidone used for?

Ziprasidone: Uses and Clinical Applications

Ziprasidone is primarily indicated for the treatment of schizophrenia and acute manic or mixed episodes associated with bipolar disorder, with or without psychotic features. 1, 2

Primary FDA-Approved Indications

• Schizophrenia: Approved for treatment of symptoms including hallucinations, delusions, paranoia, and social withdrawal 2
• Bipolar Disorder:
  • Acute manic or mixed episodes (with or without psychotic features)
  • Maintenance treatment of bipolar disorder when added to lithium or valproate 2
• Acute Agitation: Intramuscular ziprasidone is approved for acute agitation in patients with schizophrenia 3

Dosing and Administration

• Initial dose: 20 mg twice daily with food
• Target dose range: 120-160 mg/day (40-80 mg twice daily) for optimal symptom control
• Must be taken with food (≥500 kcal meal) to ensure proper absorption 1, 4
• Bioavailability is reduced by approximately 60% when taken without food 4

Mechanism and Pharmacology

Ziprasidone is an atypical (second-generation) antipsychotic with:

• Serotonin-2A (5-HT2A) and dopamine-2 (D2) receptor antagonism
• 5-HT1A receptor agonist activity
• Weak inhibition of serotonin and norepinephrine reuptake 5

Advantages in Clinical Practice

• Metabolic Profile: Unlike many other antipsychotics, ziprasidone:

  • Does not cause clinically significant weight gain
  • Does not adversely affect cholesterol, triglycerides, or glycemic control
  • May improve these parameters when switching from other antipsychotics 1, 3

• Other Favorable Characteristics:

  • Low extrapyramidal side effect liability
  • No significant persistent effects on prolactin levels
  • Not anticholinergic 3

Important Safety Considerations

• QTc Prolongation: Can prolong the QTc interval on ECG (average of 20 msec), requiring caution in:

  • Patients with pre-existing cardiac conditions
  • Those taking other medications that prolong QTc 1, 2
  • Baseline and periodic ECG monitoring recommended

• Contraindications:

  • History of QT prolongation
  • Recent acute myocardial infarction
  • Uncompensated heart failure
  • Concurrent use of other QT-prolonging medications 2
  • Elderly patients with dementia-related psychosis (increased mortality risk) 1, 2

• Common Side Effects:

  • Somnolence
  • Headache
  • Nausea
  • Dizziness 2, 5

Special Populations

• Bipolar Disorder in Children/Adolescents: Limited data, but ziprasidone is mentioned as a treatment option in guidelines for pediatric bipolar disorder 6

• Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates; pregnancy registry available to monitor outcomes 2

• Elderly: Not recommended for dementia-related psychosis due to increased mortality risk 2

Monitoring Recommendations

• Baseline and periodic ECG for QTc prolongation
• Regular assessment of therapeutic response
• Monitoring of weight and metabolic parameters
• Complete blood count monitoring in patients with pre-existing low WBC or history of drug-induced leukopenia/neutropenia 2

Ziprasidone offers an effective treatment option for schizophrenia and bipolar disorder with a favorable metabolic profile compared to many other antipsychotics, but requires careful consideration of cardiac risks and proper administration with food to ensure efficacy.