8cited
checked 2026-08-05
what it isA second generation antipsychotic that stays weight neutral where others do not; it needs a substantial meal to absorb at all and an ECG in anyone with cardiac risk
what it doesActs as an antagonist at Serotonin 5-HT2A receptor (HTR2A), one of 5 targets.what you would noticeCovers manic and mixed episodes as wellMetabolically mild by the standards of its class
is it safean atypical antipsychotic and the most QT prolonging of its class, it needs an ECG in anyone with cardiac risk, must be taken with a substantial meal to absorb at all, and carries the class…in its favour: human data in the cited literature
MoodPrescriptionSerious Drug
classAntipsychotic · Dopamine/Serotonin Antagonist · Serotonergic
key targetSerotonin 5-HT2A receptor (HTR2A) · Antagonist · Strong
targets5
literature1995 to 2022 · 7 journals
also known asZipral, Geodon, Zeldox, CP-88059 and 2 more
outlets1 outlet
spec sheet7 rows
classAntipsychotic · Dopamine/Serotonin Antagonist · Serotonergic
key targetSerotonin 5-HT2A receptor (HTR2A) · Antagonist · Strong
targets5
literature1995 to 2022 · 7 journals
also known asZipral, Geodon, Zeldox, CP-88059 and 2 more
outlets1 outlet
all namesZipral, Geodon, Zeldox, CP-88059, ziprasidone hydrochloride, ziprasidone mesylate
evidence over time
19952 in 20132022
Ziprasidone is a second generation antipsychotic used for schizophrenia and for manic or mixed episodes in bipolar disorder.
works for
- Second generation antipsychotic for schizophrenia and bipolar episodes
- Comparatively weight neutral where other antipsychotics pile it on
- A real advantage for anyone burned by metabolic weight gain
- Absorption roughly doubles when taken with a substantial meal
- Covers manic and mixed episodes as well
- Metabolically mild by the standards of its class
Gallery
did you know
- QT prolongation is the defining clinical fact about ziprasidone and it is quantified. In the FDA-requested randomised head-to-head study of six antipsychotics at steady-state peak plasma concentration, ziprasidone 160 mg/day produced a mean QTc increase of approximately 16 ms on monotherapy and approximately 21 ms with a CYP450 inhibitor added; roughly double haloperidol (about 7 ms) and olanzapine (about 7 ms), and above quetiapine (about 15 ms) and risperidone (about 12 ms), but well below thioridazine (about 30-36 ms) [2]. The main loop should read the exact millisecond values from Table 2 of that paper before publishing them.
- Critically, that same trial found no patient on any of the six drugs exceeded a mean QTc of 500 ms, and metabolic inhibition did not significantly augment QTc prolongation for any agent; the CYP interaction fear was not borne out [2].
- In the 2019 network meta-analysis of 32 antipsychotics, QTc prolongation ranged from -2.21 ms (lurasidone) to +23.90 ms (sertindole) across 15,467 participants; ziprasidone sits near the top of that range [5].
- ZODIAC is the definitive real-world answer: 18,154 patients randomised to ziprasidone or olanzapine in naturalistic practice across 18 countries. One-year non-suicide mortality was 0.91 versus 0.90 per 100 patients, relative risk 1.02 (95% CI 0.76-1.39). Re-adjudication of 205 fatal events at FDA request confirmed no difference in sudden death, RR 1.11 (95% CI 0.45-2.77) (PMID 21041245, PMID 21796719). The authors state plainly that the study was neither powered nor designed to detect events as rare as torsade de pointes; that caveat must travel with the reassurance.
- Ziprasidone is the most metabolically favourable antipsychotic in the class: it had the smallest weight change of all 32 drugs versus placebo, -0.16 kg (95% CrI -0.73 to 0.40) [5]. Efficacy is mid-range, SMD 0.39 versus placebo [6].
- Ziprasidone must be taken with a meal of at least 500 kcal; food roughly doubles its absorption, and taking it fasted can halve exposure and cause apparent treatment failure.
Mechanism
It antagonises and receptors with a higher 5-HT2A to D2 ratio than the older agents, and it also blocks and noradrenaline reuptake weakly. It is comparatively weight neutral and metabolically mild, which is its main advantage over olanzapine.
receptor fingerprint
reading the marksactivatesblocks / inhibitsmodulates
01
receptor (HTR2A)Antagonist
strong
The highest in vitro / affinity ratio of any clinically available antipsychotic at the time of approval; the proposed basis of its low extrapyramidal burden (PMID 7562537)
02
receptor (DRD2)Antagonist
strong
Antipsychotic efficacy; standardised mean difference versus placebo 0.39 (95% CrI 0.30-0.49) across 212 trials, mid-pack among 15 antipsychotics (PMID 23810019)
03
5-HT2C receptor (HTR2C)Antagonist
strongKi approx. 1.3 nM (Seeger et al. 1995, PMID 7562537). Curated mechanism in ChEMBL
Contributes to the receptor profile; notably ziprasidone remains the most weight-neutral antipsychotic despite 5-HT2C antagonism; mean difference versus placebo -0.16 kg (95% CrI -0.73 to 0.40), the best of 32 drugs (PMID 31303314)
04
hERG potassium channel (KCNH2, IKr)Blocker
strong
No benefit; this is the defining liability. A VigiBase disproportionality analysis of 20 antipsychotics ranked ziprasidone second only to sertindole for QT-prolongation reporting risk, and found a positive correlation between hERG affinity and QT reporting (PMID 36515735)
05
receptor (HTR1A)Agonist (partial)
moderate
Proposed contribution to effects on negative and depressive symptoms and to reduced extrapyramidal liability
Safetyrisks and cautions, not medical advice
an atypical antipsychotic and the most QT prolonging of its class, it needs an ECG in anyone with cardiac risk, must be taken with a substantial meal to absorb at all, and carries the class warning on increased mortality in elderly people with dementia
Subjective profileweighing the evidence above
Two practical facts decide whether this drug works for someone, and both routinely get missed. Absorption roughly doubles when it goes down with a substantial meal, so a patient swallowing it on an empty stomach may simply be untreated and then labelled treatment resistant. The second is the ECG: this is the most QT prolonging antipsychotic in common use, and cardiac disease, an electrolyte disturbance or another QT prolonging medicine all have to be checked rather than assumed. Where it earns its place is in someone who put on a great deal of weight on a more metabolically active agent, because staying weight neutral is a real clinical advantage and not a marketing one.
Where to buy
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Suppliers
Vendors carrying Ziprasidone, with live product details and codes. Links are affiliate links that support the wiki at no cost to you.
RUPharma🌐
Ziprasidone
From$11
Options$11 to $279
ShipsWorldwide from Russia and India; 3 to 4 weeks to the US and Canada, and 4 to 7 days on the lines that ship express from India, Singapore or China. Europe and Asia are select destinations rather than every country
Research
- 1995first citedZiprasidone (CP-88,059): a new antipsychotic with combined dopamine and serotonin receptor anta…
- 2019meta-analysisComparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adul…
- 2022most recentAntipsychotics and risk of QT prolongation: a pharmacovigilance study
- 1.Ziprasidone (CP-88,059): a new antipsychotic with combined dopamine and serotonin receptor antagonist activity
- 2.A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition
- 3.Comparative mortality associated with ziprasidone and olanzapine in real-world use among 18,154 patients with schizophrenia: The Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC)
- 4.Methodological challenges in the coding and adjudication of sudden deaths in a large simple trial with observational follow-up: the ziprasidone observational study of cardiac outcomes (ZODIAC)
- 5.Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis
- 6.Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis
- 7.Antipsychotics and risk of QT prolongation: a pharmacovigilance study
- 8.QTc prolongation, torsades de pointes, and psychotropic medications
8 listed here; entry last updated August 2026
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Notes and cautions
- Ziprasidone carries a boxed warning; but it is the antipsychotic class warning for increased mortality in elderly patients with dementia-related psychosis, not a QT warning.
- The QT issue sits in Warnings and Contraindications, and it is absolute: ziprasidone is contraindicated in known QT prolongation, recent acute myocardial infarction, uncompensated heart failure, and with any other QT-prolonging drug, and hypokalaemia and hypomagnesaemia must be corrected before and during treatment.
- The measured mean QTc increase is roughly 16-21 ms, about twice that of haloperidol or olanzapine but well under thioridazine, and it is not worsened by CYP inhibition [2].
- Against that, the 18,154-patient ZODIAC trial found no excess non-suicide mortality or sudden death versus olanzapine, while explicitly stating it could not exclude a rare torsade signal [3].
- The honest framing is a real, measurable, dose-related electrophysiological effect with no demonstrated mortality excess in ordinary use; and an unusually clean metabolic profile that is the main reason to choose it.
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