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Atypical Antipsychotic — D2/5-HT2A Antagonist (Low Metabolic Risk) Pregnancy: Avoid unless essential — risk of neonatal extrapyramidal symptoms in third trimester. QTc prolongation adds risk in pregnancy (physiological QTc increase). Discuss risks/benefits with specialist.

Ziprasidone

Brand names: Geodon, Zeldox

Adult dose

Dose: Schizophrenia: 20–80 mg twice daily with food. Bipolar mania (acute): 40–80 mg twice daily with food
Route: Oral (with food — mandatory)
Frequency: Twice daily with food
Max: 160 mg/day (schizophrenia); 160 mg/day (bipolar mania)
Must be taken with food (bioavailability doubles — from 20% to 40% with food). QTc prolongation requires pre-treatment ECG. Not widely used in UK (not NICE-approved for schizophrenia as first-line) but used in patients with significant metabolic syndrome where other antipsychotics are contraindicated. IM formulation 10–20 mg available for acute agitation. Source: BNF 90.

Paediatric dose

Dose: Not licensed under 18 years in UK for psychiatric indications N/A/kg
Route: N/A
Frequency: N/A
Max: N/A
Not licensed for paediatric use in UK.

Dose adjustments

Renal

No dose adjustment required — ziprasidone is >99% hepatically metabolised; renal excretion negligible.

Hepatic

Severe hepatic impairment: use with caution — increased exposure. No specific dose recommendations from manufacturer.

Paediatric weight-based calculator

Not licensed for paediatric use in UK.

Clinical pearls

  • The 'metabolically friendly' antipsychotic: ziprasidone has consistently shown minimal weight gain, minimal glucose elevation, and minimal dyslipidaemia in comparative trials (CATIE trial — ziprasidone group had lowest metabolic burden). In patients with pre-existing type 2 diabetes, obesity, or severe dyslipidaemia who require an antipsychotic, ziprasidone is a rational choice alongside aripiprazole and lurasidone.
  • CATIE trial: large NIMH-funded head-to-head trial comparing olanzapine, quetiapine, risperidone, ziprasidone, and perphenazine in schizophrenia. Olanzapine had best efficacy (discontinuation rate) but highest metabolic burden. Ziprasidone had the lowest metabolic effects but slightly lower tolerability (akathisia). No single drug was clearly superior — guide choice by side-effect profile and patient preference.
  • QTc monitoring protocol: ECG at baseline. If QTc >450 ms in men or >470 ms in women — do not start. Correct any electrolyte abnormalities (K+, Mg2+) before starting. Repeat ECG after dose titration. Patients should be counselled to report palpitations, light-headedness, or syncope.
  • Food is not optional: bioavailability doubles with food. Patients who skip meals will receive sub-therapeutic drug levels — inadequate psychosis control. Counsel explicitly: 'This tablet must be taken with food — at least 500 kcal of food — twice daily without fail'. This is one of the most clinically important food interactions in psychiatry.
  • Not widely promoted in UK: ziprasidone is not in NICE NG185 (schizophrenia) as a named option due to insufficient UK trial data at guideline development, but is available and can be used off-formulary. It is widely used in USA and is a first-line option in BAP guidelines for patients with metabolic risk. Source: BNF 90; Lieberman et al. NEJM 2005 (CATIE); BAP Schizophrenia Guidelines; MHRA SPC Zeldox.

Contraindications

  • QTc >500 ms at baseline
  • Recent acute myocardial infarction or uncompensated heart failure
  • History of cardiac arrhythmia
  • Concurrent QTc-prolonging drugs (most significant: antiarrhythmics class IA/III, sotalol, amiodarone, halofantrine, arsenic trioxide)
  • Hypokalaemia or hypomagnesaemia (reduces threshold for torsades)

Side effects

  • QTc prolongation (most important — dose-dependent; average 10 ms prolongation; torsades de pointes rare)
  • Somnolence, dizziness (mild)
  • Nausea (take with food significantly reduces this)
  • Extrapyramidal symptoms (akathisia, parkinsonism — at higher doses)
  • Rash (rare — discontinue if severe)
  • Minimal weight gain (key advantage — mean 0.5 kg vs 4+ kg for olanzapine in comparative studies)
  • Minimal metabolic syndrome (low H1, low M1 receptor affinity → little appetite increase, glucose disruption, or prolactin elevation)

Interactions

  • QTc-prolonging drugs (class IA/III antiarrhythmics, clarithromycin, moxifloxacin, methadone, ondansetron at high doses): additive QTc prolongation — contraindicated
  • Drugs causing electrolyte disturbance (loop diuretics, thiazides): hypokalaemia/hypomagnesaemia increase torsades risk — correct electrolytes before and during treatment
  • Ketoconazole (strong CYP3A4 inhibitor): increases ziprasidone AUC by 35% — use caution
  • Carbamazepine, rifampicin (CYP3A4 inducers): reduce ziprasidone levels — may require dose increase
  • Antihypertensives: additive hypotension

Monitoring

  • ECG at baseline and after dose changes (QTc monitoring — avoid if QTc >500 ms)
  • Serum electrolytes (potassium, magnesium) at baseline and if risk factors for electrolyte disturbance
  • Weight and BMI at baseline, 1 month, 3 months, then 6-monthly (expect minimal change)
  • Fasting glucose and lipid profile at baseline and annually (minimal effect expected)
  • Blood pressure (standing and sitting — orthostatic hypotension on initiation)
  • Extrapyramidal symptoms (AIMS scale every 6 months — tardive dyskinesia monitoring)

Reference: BNFc; BNF 90; Lieberman et al. NEJM 2005 (CATIE trial); BAP Guidelines for Schizophrenia; MHRA SPC Zeldox/Geodon. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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