What are the indications for ziprasidone (Geodon)?

Indications for Ziprasidone

Ziprasidone is FDA-approved for the treatment of schizophrenia in adults, acute manic or mixed episodes associated with bipolar I disorder as monotherapy, and as an adjunct to lithium or valproate for maintenance treatment of bipolar I disorder. 1

FDA-Approved Indications

Schizophrenia

• Ziprasidone is indicated for the treatment of schizophrenia in adults at doses of 20-80 mg twice daily with food 1
• The intramuscular formulation (10-20 mg IM) is approved for acute agitation in schizophrenia, with onset of action within 15-30 minutes 2
• Maintenance treatment has demonstrated efficacy in preventing relapse in patients who were symptomatically stable 1

Bipolar I Disorder

• Ziprasidone is approved as monotherapy for acute treatment of manic or mixed episodes in adults with bipolar I disorder 1
• It is also approved as adjunctive therapy to lithium or valproate for maintenance treatment of bipolar I disorder 1
• The typical dosing range for acute mania is 40-80 mg twice daily with food 3

Important Off-Label Uses

Acute Agitation in Emergency Settings

• Ziprasidone 20 mg IM is highly effective for rapid reduction of acute agitation with onset within 15 minutes, regardless of underlying cause (psychiatric disorders, alcohol intoxication, substance-induced states) 4, 2
• The 20 mg IM dose shows superior efficacy compared to lower doses and comparable efficacy to haloperidol plus lorazepam, with fewer extrapyramidal side effects 4
• Maximum daily IM dose is 40 mg/day, with repeat dosing possible every 2-4 hours as needed 2

Antiemetic Use in Gastroparesis

• Ziprasidone can be used off-label as an antiemetic for nausea and vomiting in gastroparesis due to its dopamine-receptor blocking effects, similar to phenothiazine antipsychotics 4, 5

Critical Prescribing Considerations

Administration Requirements

• Oral ziprasidone must be administered with food (500 kcal meal) to ensure adequate absorption; otherwise, bioavailability is substantially reduced and cannot be compensated by dose increases 6
• Capsules must be swallowed whole and not opened, crushed, or chewed 1

Cardiac Safety Concerns

• Ziprasidone prolongs the QTc interval more than several other antipsychotics, which should lead prescribers to consider other drugs first in most cases 1
• Ziprasidone is contraindicated in patients with recent acute myocardial infarction, baseline QT prolongation, or those taking other QT-prolonging medications 4
• Avoid in patients at risk for torsades de pointes 4

Metabolic Advantages

• Ziprasidone is one of the most weight-neutral antipsychotics with minimal impact on cholesterol, triglycerides, or glycemic control 4, 2
• This metabolic profile makes it particularly suitable for patients with metabolic concerns or those switching from other antipsychotics that caused weight gain 4, 6

Common Pitfalls to Avoid

• Do not prescribe oral ziprasidone without emphasizing the requirement for administration with a substantial meal (500 kcal), as this is the most common cause of treatment failure 6
• Do not use ziprasidone for hiccups—there is no evidence supporting this indication and safer alternatives exist 5
• Do not overlook cardiac screening before initiation, particularly ECG assessment for QTc prolongation 4, 1
• Ensure adequate dosing: target 120-160 mg/day for optimal symptom control in schizophrenia, as lower doses may result in suboptimal efficacy 6