Medication approval journey
ziprasidone (Geodon)
Approved for Schizophrenia; acute bipolar mania
Before changing anything
Stopping abruptly can be dangerous — never do it without medical supervision
Do not stop an antipsychotic abruptly. Abrupt withdrawal can cause rebound or supersensitivity psychosis and withdrawal movement disorders, and relapse risk is highest with the fastest reductions. Any change should be a slow, prescriber-supervised taper.
How long the trials actually ran
We could not establish a longest trial length for ziprasidone. That is a gap in what we can show you — not evidence that the trials ran long.
The label carries a clinical studies section describing the trials the approval rested on.
The gap between how long the trials ran and how long people actually take these medications is the single most important thing on this page. It is not evidence that longer use is unsafe or ineffective. It is evidence that longer use was not what got tested.
The boxed warning
The strongest warning the FDA puts on a label, reproduced word for word — not our summary of it.
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Ziprasidone capsules are not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions ( 5.1 )] . WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS See full prescribing information for complete boxed warning . Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Ziprasidone capsules are not approved for the treatment of patients with dementia-related psychosis. ( 5.1 )
FDA label effective August 11, 2026 — read the full label on DailyMed
How many Americans take ziprasidone
Survey-based federal estimates, published with a lag of about two years. They count prescriptions filled, not outcomes.
- 1,262,673
- prescriptions in the United States (2020)
- 189,620
- people filling them (2020)
Prescriptions are down 20% since 2014. Whatever you decide about ziprasidone, you are deciding alongside about 189,620 other people this year.
Source: ClinCalc DrugStats (Medical Expenditure Panel Survey (MEPS), Agency for Healthcare Research and Quality), CC BY-SA 4.0, release 2026.08.
What people report to the FDA about ziprasidone
Read this before the numbers.
Anyone can file an adverse event report — patients, doctors, manufacturers — and nobody verifies that the drug caused what was reported. There is no denominator: tens of millions of prescriptions generate reports at an unknowable rate, and reporting rises with news coverage, not necessarily with harm. Counts below are report volumes, not rates, and cannot be compared between drugs. The FDA itself says not to use this data to make medical decisions — we show it because you deserve to see what is in the public record, with its limits stated plainly.
- 20,025
- reports mentioning ziprasidone, all time
- 14,098
- filed as serious (a report-level flag covering every drug and outcome in the report)
Most-reported reactions
- Drug ineffective1,929
- Weight increased1,397
- Diabetes mellitus1,141
- Anxiety983
- Insomnia905
- Suicide attempt892
- Depression891
- Type 2 diabetes mellitus881
- Dyskinesia861
- Somnolence824
“Drug ineffective” ranking this high is worth noticing: a report of not being helped counts as an adverse event too, and people file them in large numbers.
Source: FDA Adverse Event Reporting System (FAERS), via openFDA, data through 2026-07-30.
Known interactions, from the label
The FDA label’s interactions section, verbatim. A pharmacist checking your actual medication list beats any published list — including this one.
Read the label’s interactions section
7 DRUG INTERACTIONS Drug-drug interactions can be pharmacodynamic (combined pharmacologic effects) or pharmacokinetic (alteration of plasma levels). The risks of using ziprasidone in combination with other drugs have been evaluated as described below. All interactions studies have been conducted with oral ziprasidone. Based upon the pharmacodynamic and pharmacokinetic profile of ziprasidone, possible interactions could be anticipated: Ziprasidone should not be used in combination with other drugs that have demonstrated QT prolongation. ( 4.1 , 7.3 ) The absorption of ziprasidone is increased up to two-fold in the presence of food. ( 7.10 ) The full prescribing information contains additional drug interactions. ( 7 ).
7.1 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 clinically relevant inhibitors or inducers of aldehyde oxidase. Less than one-third of ziprasidone metabolic clearance is mediated by cytochrome P450 catalyzed oxidation.
7.2 In Vitro Studies An in vitro enzyme inhibition study utilizing human liver microsomes showed that ziprasidone had little inhibitory effect on CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, and thus would not likely interfere with the metabolism of drugs primarily metabolized by these enzymes. There is little potential for drug interactions with ziprasidone due to displacement [see Clinical Pharmacology (12.3) ] .
7.3 Pharmacodynamic Interactions Ziprasidone should not be used with any drug that prolongs the QT interval [see Contraindications ( 4.1 )]. Given the primary CNS effects of ziprasidone, caution should be used when it is taken in combination with other centrally acting drugs. Because of its potential for inducing hypotension, ziprasidone may enhance the effects of certain antihypertensive agents. Ziprasidone may antagonize the effects of levodopa and dopamine agonists. Risk of serotonin syndrome with concomitant therapy with other serotonergic drugs such as SNRIs, SSRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John’s Wort [see Contraindications ( 4.3 ), Warnings and Precautions ( 5.4 ), Adverse Reactions ( 6.2 )].
7.4 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 ziprasidone. This effect may be greater when higher doses of carbamazepine are administered. Ketoconazole Ketoconazole, a potent inhibitor of CYP3A4, at a dose of 400 mg QD for 5 days, increased the AUC and C max of ziprasidone by about 35 to 40%. Other inhibitors of CYP3A4 would be expected to have similar effects. Cimetidine Cimetidine at a dose of 800 mg QD for 2 days did not affect ziprasidone pharmacokinetics. Antacid The co-administration of 30 mL of Maalox ® with ziprasidone did not affect the pharmacokinetics of ziprasidone.
7.5 Lithium Ziprasidone at a dose of 40 mg twice daily administered concomitantly with lithium at a dose of 450 mg twice daily for 7 days did not affect the steady-state level or renal clearance of lithium. Ziprasidone dosed adjunctively to lithium in a maintenance trial of bipolar patients did not affect mean therapeutic lithium levels.
7.6 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 the pharmacokinetics of concomitantly administered oral contraceptives, ethinyl estradiol (0.03 mg) and levonorgestrel (0.15 mg).
7.7 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 major metabolite, dextrorphan. There was no statistically significant change in the urinary dextromethorphan/dextrorphan ratio.
7.8 Valproate A pharmacokinetic interaction of ziprasidone with valproate is unlikely due to the lack of common metabolic pathways for the two drugs. Ziprasidone dosed adjunctively to valproate in a maintenance trial of bipolar patients did not affect mean therapeutic valproate levels.
7.9 Other Concomitant Drug Therapy Population pharmacokinetic analysis of schizophrenic patients enrolled in controlled clinical trials has not revealed evidence of any clinically significant pharmacokinetic interactions with benztropine, propranolol, or lorazepam.
7.10 Food Interaction The absolute bioavailability of a 20 mg dose under fed conditions is approximately 60%. The absorption of ziprasidone is increased up to two-fold in the presence of food [see Clinical Pharmacology (12.3) ] .
FDA label for ziprasidone, effective August 11, 2026 — DailyMed.
Who pays for ziprasidone
Two claims datasets and one survey, covering different populations with different instruments — they cannot be reconciled by arithmetic, and where their sum crowds the all-payer estimate, that is a finding about the estimates rather than a percentage.
- Medicare Part D
- 78,385 beneficiaries filled 636,774 claims in 2024 — 28,704 aged 65 and over, and 49,681 under 65. The under-65 group is not a picture of ordinary working-age adults: Medicare before 65 means the disabled and dual-eligible population — among the sickest, highest-need people in the program — and reading their utilization as typical adult use would be a category error.
- Medicaid
- At least 512,420 prescriptions in 2024 — a floor, because 176 of 583 national data rows are suppressed for privacy and contribute zero. Medicaid covers more children than any insurer in the country and publishes no age split — how much of this number is pediatric use is not knowable from public data.
- All payers (survey estimate)
- The MEPS-based estimate above puts the whole country at 1,262,673 prescriptions and 189,620 people in 2020. Subtracting the public programs from it would produce a number for everyone else — and we do not print that number, because subtracting a survey from claims counts manufactures precision that does not exist.
- The population nobody counts
- The commercially insured working-age adult — statistically, the likeliest person to be reading this page — is the one population with no public per-drug count anywhere. Private claims data exists and is sold, but nothing a patient can check is published. For children the record is thinner still: no public source counts pediatric use of ziprasidone specifically; the closest the public record comes is condition-level treatment rates for children, which we have traced for one condition in how childhood ADHD got counted.
Sources: Medicare Part D Prescribers — by Geography and Drug, data.cms.gov, National rows, data year 2024 (published with ~17-month lag). Medicaid State Drug Utilization Data 2024, data.medicaid.gov, national aggregate rows. Retrieved 2026-09-01.
The approval, step by step
Step 1
What the approval was actually based on
Which studies did the FDA rely on, how long did they run, and who was in them?
The efficacy of oral ziprasidone in the treatment of schizophrenia was evaluated in 5 placebo-controlled studies, 4 short-term (4- and 6-week) trials and one maintenance trial... Four of the 5 trials were able to distinguish ziprasidone from placebo; one short-term study did not.
FDA-approved labelling, 14 CLINICAL STUDIES — read the label on DailyMed
Our reading
Read the last sentence of that quote again, because labels rarely say it so plainly: one of the five pivotal trials could not tell ziprasidone from placebo, and the FDA printed that and approved the drug anyway — four out of five is how the standard actually works. The QT-prolongation question dominated this drug's review and its early marketing restrictions; the label's cardiac sections are the ones a prescriber will care about most, and they are the reason this drug is taken with food and not combined casually.
Step 2
The approval
When was it approved, under what application, and by whose review?
- Approved
- February 5, 2001
- Application
- NDA020825
- Review
- STANDARD
- Original sponsor
- Pfizer
- Holds it now
- Viatris
- Label submissions since
- 35
Source: openFDA Drugs@FDA, original application ORIG-1
Step 3
What was added after it was on the market
Which warnings arrived only after millions of people were already taking it?
Antipsychotics raise the risk of death in older people with dementia
This is one of the clearest harm signals in psychiatric medicine, and it applies to a specific group: older adults with dementia-related psychosis. Pooling 17 placebo-controlled trials covering 5,106 patients over roughly 10 weeks, the risk of death was 1.6 to 1.7 times higher on an antipsychotic than on placebo — about 4.5% against 2.6%. Most deaths were cardiovascular or infectious, chiefly heart failure, sudden death and pneumonia.
The FDA first applied this warning to the newer antipsychotics in 2005 and extended it to the older ones in 2008. No antipsychotic is approved for dementia-related psychosis.
If this is being prescribed for an older relative with dementia, worth asking: what specific behaviour are we treating, what have we tried that is not a drug, what is the shortest time we can plan for, and when will we review stopping.
Step 4
What independent research has found since
What has been learned by people who were not selling it?
We have not yet added independent post-approval research on ziprasidone to the evidence library. Absence here means we have not covered it, not that none exists.
Step 5
What still is not known
Which questions you might reasonably have has nobody answered yet?
- One pivotal trial failed to beat placebo and the label says so. How many prescribers quoting "proven efficacy" have read that sentence?
- The QT concern shaped the approval. What monitoring, if any, is happening now?
- Must be taken with food to absorb properly — a practical fact that quietly determines whether the prescribed dose is the received dose.
Deciding about ziprasidone?
- 12 questions to ask before starting a psychiatric medication — each with the study behind it
- Already on it? The 10-question annual review — including the honest case for staying
- How long every drug here was tested before approval — one chart, all medications
Open ziprasidone (Geodon) in Resolv
The app has the full approval journey, the resources behind it, and people working through the same questions.
