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Atypical Antipsychotic — D2/5-HT2A Antagonist (Low Metabolic Risk) Pregnancy: Overall available data from published epidemiological studies of pregnant women exposed to ziprasidone have not established a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes; there are risks to the mother from untreated schizophrenia or bipolar I disorder. Neonates exposed to antipsychotic drugs during the third trimester are at risk of extrapyramidal and/or withdrawal symptoms following delivery. In animal studies, ziprasidone caused developmental toxicity at doses similar to recommended human doses and was teratogenic in rabbits at 3 times the maximum recommended human dose. A pregnancy exposure registry for atypical antipsychotics is available (US label section 8.1).

Ziprasidone

Brand names: Geodon, Zeldox

Ziprasidone is a second-generation (atypical) antipsychotic used in the management of schizophrenia and bipolar disorder.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Schizophrenia (adults): initial 20 mg twice daily with food; the daily dosage may subsequently be adjusted on the basis of individual clinical status up to 80 mg twice daily, with dosage adjustments generally at intervals of not less than 2 days
Route: Oral (capsules administered with food; swallow whole, do not open, crush or chew)
Frequency: Twice daily, with food
Max: 80 mg twice daily — 'An increase to a dose greater than 80 mg twice daily is not generally recommended.' Efficacy was demonstrated over 20 mg to 100 mg twice daily in short-term trials; the safety of doses above 100 mg twice daily has not been systematically evaluated
US label (ziprasidone capsules, NorthStar Rx, label date 2026-06-01). No UK SPC (eMC) was present in this bundle, so the record is from US labelling and must be checked against UK/EU labelling before publication. Patients should ordinarily be observed for improvement for several weeks before upward dose adjustment, to ensure use of the lowest effective dose. Maintenance in schizophrenia: no additional benefit was demonstrated for doses above 20 mg twice daily; reassess periodically. Bipolar I disorder, acute manic or mixed episodes (adults): initial 40 mg twice daily with food, increased to 60 mg or 80 mg twice daily on the second day, then adjusted on tolerance and efficacy within the range 40 mg to 80 mg twice daily. Bipolar I maintenance as an adjunct to lithium or valproate: continue at the dose on which the patient was initially stabilised, within 40 mg to 80 mg twice daily with food. Ziprasidone must be given with food — absorption is increased up to two-fold in the presence of food. MAOI switching: allow at least 14 days after stopping an MAOI before starting ziprasidone, and at least 3 days after stopping ziprasidone before starting an MAOI. Elderly: consider a lower starting dose, slower titration and careful monitoring during the initial dosing period in some patients. Paediatrics: 'The safety and effectiveness of ziprasidone have not been established in pediatric patients... a safe and effective dose for use could not be established.' No renal dose adjustment was stated in the sections fetched. Sections 4 (contraindications), 5, 6, 7 and 8.1 were truncated at the source-fetch limit, so the lists below are not necessarily complete — in particular the label's list of QT-prolonging drugs and its 'most common adverse reactions' list were cut off.

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Known history of QT prolongation, including congenital long QT syndrome
  • Recent acute myocardial infarction
  • Uncompensated heart failure
  • Combination with other drugs that have demonstrated QT prolongation
  • Known hypersensitivity to ziprasidone
  • Concomitant use of monoamine oxidase inhibitors (MAOIs), or use within 14 days of stopping an MAOI

Side effects

  • QT interval prolongation and risk of sudden death
  • Severe cutaneous adverse reactions, including DRESS and Stevens-Johnson syndrome (sometimes fatal); rash
  • Neuroleptic malignant syndrome; serotonin syndrome
  • Tardive dyskinesia
  • Metabolic changes; orthostatic hypotension and falls
  • Leukopenia, neutropenia and agranulocytosis; seizures; hyperprolactinaemia; priapism

Interactions

  • Other QT-prolonging drugs — contraindicated; the label names dofetilide, sotalol, quinidine, other Class Ia and III antiarrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, halofantrine, mefloquine, pentamidine and arsenic (list truncated at fetch)
  • MAOIs — contraindicated; allow at least 14 days after stopping an MAOI before starting ziprasidone and at least 3 days after stopping ziprasidone before starting an MAOI
  • Food — absorption of ziprasidone is increased up to two-fold in the presence of food, so it must always be administered with food
  • About two-thirds of ziprasidone is metabolised by glutathione and aldehyde oxidase reduction (no known clinically relevant inhibitors or inducers of aldehyde oxidase); in vitro it had little inhibitory effect on CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4

Clinical monograph

How it works

It antagonises dopamine D2 and serotonin 5-HT2A receptors, with additional activity at other serotonergic and adrenergic receptors contributing to its effect.

Prescribing in practice

  • It can prolong the QT interval, so it is contraindicated in those with known QT prolongation, recent myocardial infarction or uncompensated heart failure, and caution is needed with other QT-prolonging drugs.
  • Oral absorption is substantially enhanced when taken with food, so consistency in administration is important.
  • Use with caution in those with risk factors for electrolyte disturbance, which can potentiate arrhythmia risk.

Monitoring

Monitor ECG where there are cardiac risk factors, along with electrolytes, weight and metabolic parameters.

Counselling the patient

  • Take the medicine with food to ensure it is absorbed properly.
  • Report palpitations, fainting or dizziness without delay.
  • Do not stop treatment suddenly without discussing it with your prescriber.

Evidence & guidelines

Atypical antipsychotics are established options for schizophrenia, with choice guided by side-effect profile per NICE guidance.

Reference: Lieberman et al. NEJM 2005 (CATIE trial); BAP Guidelines for Schizophrenia; MHRA SPC Zeldox/Geodon; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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