Ziprasidone

Q: What is Ziprasidone used for?

Ziprasidone is evaluated for the following indications with varying evidence strength: Schizophrenia (evidence tier A), Stress and anxiety (evidence tier F). See the full indication matrix with dosing and citations above on this page.

Q: What are the side effects of Ziprasidone?

Common side effects of Ziprasidone (≥ 1 in 100): Drowsiness, Dizziness, Dry mouth, Constipation, QT prolongation, Extrapyramidal disorders. See the Safety section for uncommon and serious reactions.

Q: Who should not take Ziprasidone?

Ziprasidone is contraindicated in: Ziprasidone hypersensitivity; QT prolongation, congenital long QT syndrome; Acute MI, decompensated heart failure; Concomitant QT-prolonging drugs; Pregnancy and lactation. Full list in the Safety section.

AEMPS

Atypical antipsychotic – indole derivative

ATC code: N05AE04

Brand names: Ziprasidona Cinfa, Geodon

Updated 26 May 2026 · Methodology

Indications

Schizophrenia

Second line

Second-line for schizophrenia per 2020. Starting dose 20 mg twice daily, titrated to 40–80 mg twice daily. Advantage: minimal metabolic impact; preferred in patients with metabolic syndrome, obesity, diabetes. Huhn 2019 network meta-analysis showed lower efficacy than olanzapine and risperidone but better metabolic tolerability.

Sources

ICD-10: F20 · ICD-11: 6A20

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Stress and anxiety

Not recommended

Ziprasidone is an antipsychotic. It is prescribed only for schizophrenia and bipolar disorder ( 2020 guidelines). For acute stress or emotional regulation, ziprasidone does not work: no clinical studies of such use exist, no evidence base supports it. The drug has severe side effects: substantial QT-interval prolongation (greater than most antipsychotics), and risk of DRESS syndrome, a severe skin reaction ( warning, 2014). If ziprasidone was prescribed for stress or emotional regulation, consider seeking a second opinion.

Sources

ICD-10: F41.9 · ICD-11: 6B0Z

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

An antagonist at dopamine D2 and serotonin 5-HT2A receptors with partial 5-HT1A agonism. Also moderate serotonin and noradrenaline reuptake inhibition (potential antidepressant component). Compared with other atypical antipsychotics, minimal metabolic profile – almost no weight gain, hyperglycemia, dyslipidemia (advantage in metabolic syndrome). Half-life 7 hours – twice-daily dosing.

Safety

Boxed warning

FDA boxed warning: increased mortality in elderly patients with dementia treated with atypical antipsychotics.

Contraindications

Ziprasidone hypersensitivity
QT prolongation, congenital long QT syndrome
Acute MI, decompensated heart failure
Concomitant QT-prolonging drugs
Pregnancy and lactation

Serious adverse effects

QT prolongation with torsades de pointes risk (highest among atypical antipsychotics)
Neuroleptic malignant syndrome
Tardive dyskinesia
Cerebrovascular events in older adults with dementia
Severe cutaneous reactions (DRESS syndrome)

Common adverse effects

Drowsiness
Dizziness
Dry mouth
Constipation
QT prolongation
Extrapyramidal disorders

Pregnancy: can you take Ziprasidone?

T3 use carries neonatal extrapyramidal and withdrawal risk.

Breastfeeding: can you take Ziprasidone?

Not used during lactation.

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Take twice daily strictly with meals containing at least 500 kcal – food doubles bioavailability. Without food, bioavailability is unpredictable. Pre-treatment ECG to assess QT; reassess every 3–6 months. With QT-prolongation risk factors (electrolyte abnormalities, concurrent QT-prolonging drugs), combination contraindicated.

Drug–drug interactions

5 pairs found. Sorted from critical to minor.

CriticalAmiodaroneClass III antiarrhythmics (Vaughan Williams)

Mechanism

Ziprasidone prolongs QT clinically (15-20 ms). With amiodarone – torsades de pointes.

Symptoms

QTc above 500 ms, syncope, torsades de pointes risk.

Management

Combination contraindicated.

Sources

Pair details →Amiodarone →

CriticalHaloperidolFirst-generation antipsychotics. Butyrophenone derivatives

Mechanism

Both drugs prolong the QT interval and the effects add up. The haloperidol label describes QTc prolongation, ventricular arrhythmias and sudden death, with higher risk at high doses, high plasma concentrations and parenteral, especially intravenous, use (4.4). Ziprasidone prolongs QT in a dose-related way. In the study cited in the label, oral ziprasidone lengthened QTc by 9–14 ms more than haloperidol; after a second intramuscular injection ziprasidone added 12.8 ms and haloperidol 14.7 ms (Geodon, 5.3). There is no kinetic component. According to its label, ziprasidone does not change the concentrations of CYP2D6 or CYP3A4 substrates to a clinically relevant degree (Zeldox, 4.5).

Symptoms

QTc prolongation on the ECG, torsade de pointes, ventricular fibrillation, sudden death. Clinically this means palpitations, dizziness, syncope or seizures: the ziprasidone label names them as reasons to suspect a malignant arrhythmia and record an ECG (Zeldox, 4.4). The risk is higher with bradycardia, hypokalaemia and hypomagnesaemia, heart disease, a family history of QT prolongation, in CYP2D6 poor metabolisers with high haloperidol concentrations, and with intravenous haloperidol (both labels).

Management

The combination is contraindicated: the AEMPS haloperidol label (sections 4.3 and 4.5) bars haloperidol with QT-prolonging drugs and names ziprasidone in the list. The ziprasidone label says it should not be given with QT-prolonging drugs (Zeldox, 4.4), and the label says to avoid the combination (Geodon, 5.3). The second antipsychotic is not added on top of the first; one replaces the other. Before starting either drug, record a baseline ECG (haloperidol label, 4.4; ziprasidone label, 4.4 – in patients with heart disease) and correct potassium and magnesium (both labels). Decide on ECG monitoring during treatment (haloperidol label, 4.4). If QTc lengthens, reduce the haloperidol dose and stop it at QTc above 500 ms (haloperidol label, 4.4). Ziprasidone is also stopped at QTc above 500 ms (Zeldox, 4.4). Palpitations, dizziness, syncope or seizures in a patient taking both call for an ECG and an arrhythmia work-up (Zeldox, 4.4). Intravenous haloperidol adds risk on its own (haloperidol label, 4.4; FDA label).

Sources

Pair details →Haloperidol →

CriticalMoxifloxacinFourth-generation fluoroquinolone

Mechanism

Dual QT prolongation (ziprasidone 15-20 ms + moxifloxacin 10-20 ms). Torsades de pointes.

Symptoms

QTc above 500 ms, syncope, torsades de pointes risk.

Management

Combination contraindicated.

Sources

Pair details →Moxifloxacin →

CriticalPimozideFirst-generation antipsychotic, diphenylbutylpiperidine derivative

Mechanism

Both antipsychotics prolong the QT interval. Ziprasidone does so dose-dependently, to a mild-to-moderate degree (ziprasidone label); in placebo-controlled trials QTc rose by about 10 ms at the highest recommended daily dose of 160 mg (ziprasidone label, ). For pimozide, there are reports of QT prolongation, torsade de pointes, ventricular tachycardia and ventricular fibrillation at therapeutic doses (pimozide label). No study of the pair exists, and both labels assume the effects add up (ziprasidone and pimozide labels). No kinetic contribution is expected: ziprasidone has little inhibitory effect on cytochrome enzymes, including CYP3A4 and CYP2D6, which metabolise pimozide (ziprasidone label). Both drugs block dopamine D2 receptors, so motor side effects and the risk of neuroleptic malignant syndrome also add up.

Symptoms

QT prolongation causes no symptoms and shows only on the ECG. The ziprasidone label names palpitations, dizziness, syncope or seizures as possible signs of a malignant arrhythmia (ziprasidone label); the pimozide label also reports sudden death and cardiac arrest (pimozide label). Double dopamine blockade presents as tremor, rigidity, akathisia and acute dystonia, and neuroleptic malignant syndrome as high fever, muscle rigidity, unstable blood pressure and pulse, and altered consciousness (both labels).

Management

The combination is contraindicated. The Spanish ziprasidone label names pimozide in its contraindications (ziprasidone label, AEMPS). The US ziprasidone label lists pimozide among the drugs that should not be given with ziprasidone (ziprasidone label, ). The Spanish pimozide label contraindicates any drug known to prolong the QT interval and stresses that its list of examples is not exhaustive (pimozide label). The US pimozide label names ziprasidone outright (pimozide label, FDA). Do not prescribe the two drugs together. If a patient on one of them needs another antipsychotic, choose one that does not prolong the QT interval, because the ban in both labels covers that whole class (ziprasidone and pimozide labels). For each drug on its own: before starting ziprasidone, correct potassium and magnesium, and in patients with stable heart disease take an ECG (ziprasidone label); on pimozide, take an ECG before the start and repeat it during treatment (pimozide label). With palpitations, dizziness, syncope or seizures, take an ECG to look for arrhythmia (ziprasidone label), and stop the drug if QTc exceeds 500 ms (ziprasidone and pimozide labels).

Sources

Pair details →Pimozide →

CriticalSotalolNon-selective beta blocker with class III antiarrhythmic activity

Mechanism

Dual QT prolongation, torsades risk.

Symptoms

QTc above 500 ms, syncope, torsades de pointes risk.

Management

Combination contraindicated.

Sources

Pair details →Sotalol →

Label mentions52 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

CriticalChlorpromazine
«CONTRAINDICATIONS: dofetilide, sotalol, quinidine, other Class Ia and III anti-arrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin…»
FDA, section 4 · Open on DailyMed
CriticalCisapride
«Tratamiento concomitante con medicamentos que prolonguen el intervalo QT como antiarrítmicos de Clase IA y III, trióxido de arsénico, halofantrina, acetato de levometadilo, mesoridazina, tioridazina…»
AEMPS, section 4.3 · Open on CIMA
CriticalDofetilide
«CONTRAINDICATIONS: dofetilide, sotalol, quinidine, other Class Ia and III anti-arrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin…»
FDA, section 4 · Open on DailyMed
CriticalDroperidol
«CONTRAINDICATIONS: dofetilide, sotalol, quinidine, other Class Ia and III anti-arrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin…»
FDA, section 4 · Open on DailyMed
CriticalLinezolid
«Monoamine Oxidase Inhibitors (MAOIs): Ziprasidone is contraindicated in patients taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of…»
FDA, section 4 · Open on DailyMed
CriticalMAO inhibitorsclass named in the label
«Monoamine Oxidase Inhibitors (MAOIs): Ziprasidone is contraindicated in patients taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of…»
FDA, section 4 · Open on DailyMed
CriticalMoxifloxacin
«Tratamiento concomitante con medicamentos que prolonguen el intervalo QT como antiarrítmicos de Clase IA y III, trióxido de arsénico, halofantrina, acetato de levometadilo, mesoridazina, tioridazina…»
AEMPS, section 4.3 · Open on CIMA
CriticalMoxifloxacin
«CONTRAINDICATIONS: dofetilide, sotalol, quinidine, other Class Ia and III anti-arrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin…»
FDA, section 4 · Open on DailyMed
CriticalPimozide
«Tratamiento concomitante con medicamentos que prolonguen el intervalo QT como antiarrítmicos de Clase IA y III, trióxido de arsénico, halofantrina, acetato de levometadilo, mesoridazina, tioridazina…»
AEMPS, section 4.3 · Open on CIMA
CriticalPimozide
«CONTRAINDICATIONS: dofetilide, sotalol, quinidine, other Class Ia and III anti-arrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin…»
FDA, section 4 · Open on DailyMed
CriticalQT-prolonging drugsclass named in the label
«CONTRAINDICATIONS: Pharmacokinetic/pharmacodynamic studies between ziprasidone and other drugs that prolong the QT interval have not been performed. An additive effect of ziprasidone and other drugs…»
FDA, section 4 · Open on DailyMed
CriticalQuinidine
«CONTRAINDICATIONS: dofetilide, sotalol, quinidine, other Class Ia and III anti-arrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin…»
FDA, section 4 · Open on DailyMed
CriticalSotalol
«CONTRAINDICATIONS: dofetilide, sotalol, quinidine, other Class Ia and III anti-arrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin…»
FDA, section 4 · Open on DailyMed
CriticalTacrolimus
«CONTRAINDICATIONS: dofetilide, sotalol, quinidine, other Class Ia and III anti-arrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin…»
FDA, section 4 · Open on DailyMed
Majorantiarrítmicosclass named in the label
«- Prolongación conocida del intervalo QT. Síndrome congénito de intervalo QT prolongado. Infarto agudo de miocardio reciente. Insuficiencia cardiaca descompensada. Arritmias tratadas con medicamentos…»
AEMPS, section 4.3 · Open on CIMA
Majormedicamentos que prolongan el QTclass named in the label
«Tratamiento concomitante con medicamentos que prolonguen el intervalo QT como antiarrítmicos de Clase IA y III, trióxido de arsénico, halofantrina, acetato de levometadilo, mesoridazina, tioridazina…»
AEMPS, section 4.3 · Open on CIMA
Minorinhibidores del CYP3A4class named in the label
«El inhibidor de la CYP3A4, ketoconazol (400 mg/día), que también inhibe la p-gp , dio lugar a un incremento de las concentraciones en suero de ziprasidona de <40%. Las concentraciones en suero de S-…»
AEMPS, section 4.5 · Open on CIMA
MinorKetoconazole
«El inhibidor de la CYP3A4, ketoconazol (400 mg/día), que también inhibe la p-gp , dio lugar a un incremento de las concentraciones en suero de ziprasidona de <40%. Las concentraciones en suero de S-…»
AEMPS, section 4.5 · Open on CIMA
antacidsclass named in the label
«Pharmacokinetic Interactions Carbamazepine: Antacid»
FDA, section 7 · Open on DailyMed
antiácidosclass named in the label
«Antiácidos - dosis múltiples de antiácidos que contienen aluminio y magnesio o de cimetidina, no tuvieron un efecto significativo desde el punto de vista clínico sobre la farmacocinética de…»
AEMPS, section 4.5 · Open on CIMA
anticonceptivos hormonalesclass named in the label
«Anticonceptivos orales - la administración de ziprasidona no provocó cambios significativos de la farmacocinética de los componentes estrogénicos (etinil estradiol, un sustrato CYP3A4) o progesterona.»
AEMPS, section 4.5 · Open on CIMA
Carbamazepine
«Pharmacokinetic Interactions Carbamazepine: Carbamazepine is an inducer of CYP3A4; administration of 200 mg twice daily for 21 days resulted in a decrease of approximately 35% in the AUC of…»
FDA, section 7 · Open on DailyMed
Dextromethorphan
«Un estudio in vivo con dextrometorfano no mostró una inhibición marcada de la CYP2D6 a concentraciones plasmáticas un 50% inferiores a las obtenidas tras la administración de 40 mg de ziprasidona dos…»
AEMPS, section 4.5 · Open on CIMA
Dextromethorphan
«Dextromethorphan: Consistent with in vitro results, a study in normal healthy volunteers showed that ziprasidone did not alter the metabolism of dextromethorphan, a CYP2D6 model substrate, to its…»
FDA, section 7 · Open on DailyMed
Estradiol
«Anticonceptivos orales - la administración de ziprasidona no provocó cambios significativos de la farmacocinética de los componentes estrogénicos (etinil estradiol, un sustrato CYP3A4) o progesterona.»
AEMPS, section 4.5 · Open on CIMA
Estradiol
«Oral Contraceptives: In vivo studies have revealed no effect of ziprasidone on the pharmacokinetics of estrogen or progesterone components. Ziprasidone at a dose of 20 mg twice daily did not affect…»
FDA, section 7 · Open on DailyMed
Glutathione
«Metabolic Pathway: Approximately two-thirds of ziprasidone is metabolized via a combination of chemical reduction by glutathione and enzymatic reduction by aldehyde oxidase. There are no known…»
FDA, section 7 · Open on DailyMed
hormonal contraceptivesclass named in the label
«Oral Contraceptives: In vivo studies have revealed no effect of ziprasidone on the pharmacokinetics of estrogen or progesterone components. Ziprasidone at a dose of 20 mg twice daily did not affect…»
FDA, section 7 · Open on DailyMed
ISRSclass named in the label
«Medicamentos serotoninérgicos: Se han notificado casos aislados de síndrome serotoninérgico asociado temporalmente con el uso terapéutico de ziprasidona en combinación con otros medicamentos…»
AEMPS, section 4.5 · Open on CIMA
Ketoconazole
«Pharmacokinetic Interactions Carbamazepine: Ketoconazole»
FDA, section 7 · Open on DailyMed
Levonorgestrel
«Oral Contraceptives: In vivo studies have revealed no effect of ziprasidone on the pharmacokinetics of estrogen or progesterone components. Ziprasidone at a dose of 20 mg twice daily did not affect…»
FDA, section 7 · Open on DailyMed
Lithium
«Litio - la administración junto con ziprasidona no tuvo efecto sobre los parámetros farmacocinéticos del litio.»
AEMPS, section 4.5 · Open on CIMA
Lithium
«Pharmacodynamic Interactions: Risk of serotonin syndrome with concomitant therapy with other serotonergic drugs such as SNRIs, SSRIs, triptans, tricyclic antidepressants, opioids, lithium…»
FDA, section 7 · Open on DailyMed

From other drugs’ labels

CriticalHaloperidol
«Efectos cardiovasculares: Otros antipsicóticos (p. ej., derivados de la fenotiazina, sertindol, pimozida, ziprasidona).»
AEMPS, section 4.5 · Open on CIMA
CriticalPimozide
«DRUG INTERACTIONS: Because pimozide prolongs the QT interval of the electrocardiogram, an additive effect on QT interval would be anticipated if administered with other drugs, such as phenothiazines…»
FDA, section 7 · Open on DailyMed
MajorIvabradine
«- Medicamentos no cardiovasculares que prolongan el intervalo QT (ej. pimozida, ziprasidona,»
AEMPS, section 4.5 · Open on CIMA
ModerateClozapine
«Potential for Other Drugs to Affect Clozapine: Use caution when administering concomitant medications that prolong the QT interval or inhibit the metabolism of clozapine. Drugs that cause QT…»
FDA, section 7 · Open on DailyMed
ModerateFluoxetine
«Drugs that Prolong the QT Interval: Do not use fluoxetine in combination with thioridazine or pimozide. Use fluoxetine with caution in combination with other drugs that cause QT prolongation. These…»
FDA, section 7 · Open on DailyMed
Carbamazepine
«Fármacos que pueden disminuir los niveles plasmáticos de carbamazepina: Antipsicóticos: clozapina, haloperidol y bromperidol, olanzapina, quetiapina, risperidona, ziprasidona, aripiprazol…»
AEMPS, section 4.5 · Open on CIMA
Donepezil
«Otros antipsicóticos (p. ej., derivados de la fenotiazina, sertindol, pimozida, ziprasidona)»
AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Ziprasidone used for?

Ziprasidone is evaluated for the following indications with varying evidence strength: Schizophrenia (evidence tier A), Stress and anxiety (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Ziprasidone?

Common side effects of Ziprasidone (≥ 1 in 100): Drowsiness, Dizziness, Dry mouth, Constipation, QT prolongation, Extrapyramidal disorders. See the Safety section for uncommon and serious reactions.

Is Ziprasidone safe during pregnancy?

T3 use carries neonatal extrapyramidal and withdrawal risk.

Is Ziprasidone compatible with breastfeeding?

Not used during lactation.

Who should not take Ziprasidone?

Ziprasidone is contraindicated in: Ziprasidone hypersensitivity; QT prolongation, congenital long QT syndrome; Acute MI, decompensated heart failure; Concomitant QT-prolonging drugs; Pregnancy and lactation. Full list in the Safety section.

Does Ziprasidone carry an FDA boxed warning?

FDA boxed warning: increased mortality in elderly patients with dementia treated with atypical antipsychotics.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 05/30/2025
FDA / DailyMedLabel dated 08/03/2026

Other drugs in this group

Zolpidem, Alprazolam, Amisulpride, Apigenin, Bromazepam, Droperidol, Lormetazepam, Phenibut