Ziprasidone

Overview

Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It may be used by mouth and by injection into a muscle (IM). The intramuscular form may be used for acute agitation in people with schizophrenia.[1] WP

Common side effects include tremors, tics, dizziness, dry mouth, restlessness, nausea, and mild sedation. Although it can also cause weight gain, the risk is much lower than for other atypical antipsychotics. How it works is not entirely clear but is believed to involve effects on serotonin and dopamine in the brain.[1–4] WP

Ziprasidone was approved for medical use in the United States in 2001. The pills are made up of the hydrochloride salt, ziprasidone hydrochloride. The intramuscular form is the mesylate, ziprasidone mesylate trihydrate, and is provided as a lyophilized powder. In 2020, it was the 282nd most commonly prescribed medication in the United States, with more than 1 million prescriptions.[1][5][6] WP

Uses, dosage and effects

Medical uses

Ziprasidone is approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia as well as acute mania and mixed states associated with bipolar disorder. Its intramuscular injection form is approved for acute agitation in schizophrenic patients for whom treatment with just ziprasidone is appropriate.[7] WP

In a 2013 study in a comparison of 15 antipsychotic drugs in effectiveness in treating schizophrenic symptoms, ziprasidone demonstrated mild-standard effectiveness. Ziprasidone was 15% more effective than lurasidone and iloperidone, approximately as effective as chlorpromazine and asenapine, and 9–13% less effective than haloperidol, quetiapine, and aripiprazole. Ziprasidone is effective in the treatment of schizophrenia, though evidence from the CATIE trials suggests it is less effective than olanzapine, and equally as effective compared to quetiapine. There are higher discontinuation rates for lower doses of ziprasidone, which are also less effective than higher doses.[8][9] WP

Correspondence to clinical effects

Ziprasidone mostly affects the receptors of dopamine (D₂), serotonin (5-HT2A, partially 5-HT1A, 5-HT2C, and 5-HT1D) and epinephrine/norepinephrine (α₁) to a high degree, while of histamine (H₁) - moderately. It also somewhat inhibits reuptake of serotonin and norepinephrine, though not dopamine.[10–15] WP

Ziprasidone's efficacy in treating the positive symptoms of schizophrenia is believed to be mediated primarily via antagonism of the dopamine receptors, specifically D₂. Blockade of the 5-HT2A receptor may also play a role in its effectiveness against positive symptoms, though the significance of this property in antipsychotic drugs is still debated among researchers. Blockade of 5-HT2A and 5-HT2C and activation of 5-HT1A as well as inhibition of the reuptake of serotonin and norepinephrine may all contribute to its ability to alleviate negative symptoms.; however, its effects on the 5-HT1A receptor may be limited as a study found ziprasidone would likely "produce detectable occupancy [of 5-HT1A receptors] only at higher doses that would produce unacceptable levels of side effects in man, although lower doses are sufficient to produce pharmacological effects." The relatively weak antagonistic actions of ziprasidone on the α₁-adrenergic receptor likely in part explains some of its side effects, such as orthostatic hypotension. Unlike many other antipsychotics, ziprasidone has no significant affinity for the mACh receptors, and as such lacks any anticholinergic side effects. Like most other antipsychotics, ziprasidone is sedating due primarily to serotonin and dopamine blockade.[16–20] WP

It has also been identified as a potent vesicular monoamine transporter 2 (VMAT2) inhibitor (IC₅₀ (half-maximal inhibitory concentration) = 15 nM).[21] WP

Risks and side effects

Adverse effects

Ziprasidone (and all other second generation antipsychotics (SGAs)) received a boxed warning in the US due to increased mortality in elderly people with dementia-related psychosis.[22] WP

Sleepiness and headache are very common adverse effects (>10%).[2][3] WP

Common adverse effects (1–10%), include producing too much saliva or having dry mouth, runny nose, respiratory disorders or coughing, nausea and vomiting, stomach aches, constipation or diarrhea, loss of appetite, weight gain (but the smallest risk for weight gain compared to other antipsychotics), rashes, fast heart beats, blood pressure falling when standing up quickly, muscle pain, weakness, twitches, dizziness, and anxiety. Extrapyramidal symptoms are also common and include tremor, dystonia (sustained or repetitive muscle contractions), akathisia (the feeling of a need to be in motion), parkinsonism, and muscle rigidity; in a 2013 meta-analysis of 15 antipsychotic drugs, ziprasidone ranked 8th for such side effects.[2][3][4][23] WP

Ziprasidone is known to trigger mania in some bipolar patients.[24][25][26] WP

This medication can cause birth defects, according to animal studies, although this side effect has not been confirmed in humans.[22] WP

Recently, the FDA required the manufacturers of some atypical antipsychotics to include a warning about the risk of hyperglycemia and Type II diabetes with atypical antipsychotics. Some evidence suggests that ziprasidone does not cause insulin resistance to the degree of other atypical antipsychotics, such as olanzapine. Weight gain is also less of a concern with ziprasidone compared to other atypical antipsychotics. In fact, in a trial of long term therapy with ziprasidone, overweight patients (BMI > 27) actually had a mean weight loss overall. According to the manufacturer insert, ziprasidone caused an average weight gain of 2.2 kg (4.8 lbs), which is significantly lower than other atypical antipsychotics, making this medication better for patients that are concerned about their weight. In December 2014, the FDA warned that ziprasidone could cause a potentially fatal skin reaction, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), although this was believed to occur only rarely.[22][27–31] WP

Discontinuation

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly there may be a feeling of the world spinning, numbness, or muscle pains. Symptoms generally resolve after a short period of time.[32][33] WP

There is tentative evidence that discontinuation of antipsychotics can result in psychosis. It may also result in reoccurrence of the condition that is being treated. Rarely tardive dyskinesia can occur when the medication is stopped.[33][34][35] WP

Pharmacology

Pharmacokinetics

The systemic bioavailability of ziprasidone is 100% when administered intramuscularly and 60% when administered orally without food.[10] WP

After a single dose intramuscular administration, the peak serum concentration typically occurs at about 60 minutes after the dose is administered, or earlier. Steady state plasma concentrations are achieved within one to three days. Exposure increases in a dose-related manner and following three days of intramuscular dosing, little accumulation is observed.[36] WP

The bioavailability of the drug is reduced by approximately 50% if a meal is not eaten before Ziprasidone ingestion.[22][37] WP

Ziprasidone is hepatically metabolized by aldehyde oxidase; minor metabolism occurs via cytochrome P450 3A4 (CYP3A4). Medications that induce (e.g. carbamazepine) or inhibit (e.g. ketoconazole) CYP3A4 have been shown to decrease and increase, respectively, blood levels of ziprasidone.[38][39][40] WP

Its biological half-life time is 10 hours at doses of 80–120 milligrams.[41] WP

Research

Research

Ziprasidone has been studied in and reported to be effective in the treatment of borderline personality disorder, but findings are mixed.[42–45] WP

History

History

Ziprasidone is chemically similar to risperidone, of which it is a structural analogue. It was first synthesized in 1987 at the Pfizer central research campus in Groton, Connecticut.[46][47][48] WP

Phase I trials started in 1995. In 1998 ziprasidone was approved in Sweden. After the FDA raised concerns about long QT syndrome, more clinical trials were conducted and submitted to the FDA, which approved the drug on February 5, 2001.[49–53] WP

Legal status

Lawsuits

In September 2009, the U.S. Justice Department announced that Pfizer had been ordered to pay a historic fine of $2.3 billion as a penalty for fraudulent marketing of several drugs, including Geodon.[54] WP

Matthew Dougherty, a 51‑year‑old former teacher and artist with a diagnosis of schizophrenia, died on May 21, 2024, at Phoenixville Hospital in Phoenixville, Pennsylvania. According to a wrongful death lawsuit filed by his family in March 2025, Dougherty had been admitted to the hospital after a mental health crisis during which he was tased by police and suffered injuries. While hospitalized, Dougherty's regular psychiatric medications were discontinued. On the evening of his death, an alarm sounded in a nearby room, causing him to become agitated. Hospital staff called the police to restrain him, and responding officers again used a taser on Dougherty. Shortly afterward, nurses administered two doses of Geodon (ziprasidone) – a total of 40 mg, an amount the lawsuit equated to "administering poison". Minutes later, Dougherty went into cardiac arrest and could not be resuscitated. The lawsuit names as defendants Tower Health, which operates Phoenixville Hospital, and seeks damages for wrongful death and negligence. At the time the suit was filed, Tower Health had not filed a response to the complaint.[55] WP

Brand names

In the US, Geodon is marketed by Viatris after Upjohn was spun off from Pfizer.[56][57][58] WP

Chemistry

Formula

C21H21ClN4OS PC

CAS number

146939-27-7 PC

Molar mass (g/mol)

412.9 PC

IUPAC name (computed by PubChem)

5-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]-6-chloro-1,3-dihydroindol-2-one PC

SMILES

C1CN(CCN1CCC2=C(C=C3C(=C2)CC(=O)N3)Cl)C4=NSC5=CC=CC=C54 PC

InChIKey

MVWVFYHBGMAFLY-UHFFFAOYSA-N PC

PubChem CID

60854

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Ziprasidone Monograph for Professionals
2. Other Product Information: Zeldox IM (ziprasidone mesilate). February 24, 2016
3. Other Product Information: Zeldox (ziprasidone hydrochloride). February 24, 2016
4. Journal / agency FDA Psychopharmacological Drugs Advisory Committee. Briefing Document for Zeldoz Capsules. July 19, 2000
5. Other The Top 300 of 2020
6. Other Ziprasidone - Drug Usage Statistics
7. Other Pfizer to pay $2.3 billion to resolve criminal and civil health care liability relating to fraudulent marketing and the payment of kickbacks
8. Journal / agency Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. September 2013. doi:10.1016/S0140-6736(13)60733-3 · PMID 23810019
9. Journal / agency Citrome L, Yang R, Glue P, Karayal ON. Effect of ziprasidone dose on all-cause discontinuation rates in acute schizophrenia and schizoaffective disorder: a post-hoc analysis of 4 fixed-dose randomized clinical trials. Schizophrenia Research. June 2009. doi:10.1016/j.schres.2009.03.009 · PMID 19375893
10. Journal / agency Mattei C, Rapagnani MP, Stahl SM. Ziprasidone hydrocloride: what role in the management of schizophrenia?. Journal of Central Nervous System Disease. February 2011. doi:10.4137/JCNSD.S4138 · PMID 23861634 · PMC3663608
11. Journal / agency Seeger TF, Seymour PA, Schmidt AW, Zorn SH, Schulz DW, Lebel LA, McLean S, Guanowsky V, Howard HR, Lowe JA. Ziprasidone (CP-88,059): a new antipsychotic with combined dopamine and serotonin receptor antagonist activity. The Journal of Pharmacology and Experimental Therapeutics. October 1995. doi:10.1016/S0022-3565(25)12023-5 · PMID 7562537
12. Other Brunton L. Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th Edition. 2011
13. Other Akiskal HS, Tohen M. Bipolar Psychopharmacotherapy: Caring for the Patient. June 24, 2011
14. Journal / agency Nemeroff CB, Lieberman JA, Weiden PJ, Harvey PD, Newcomer JW, Schatzberg AF, Kilts CD, Daniel DG. From clinical research to clinical practice: a 4-year review of ziprasidone. CNS Spectrums. November 2005. doi:10.1017/S1092852900019842 · PMID 16381088
15. Journal / agency Tatsumi M, Jansen K, Blakely RD, Richelson E. Pharmacological profile of neuroleptics at human monoamine transporters. European Journal of Pharmacology. March 1999. doi:10.1016/S0014-2999(99)00005-9 · PMID 10193665
16. Other Lüllmann H, Mohr K. Pharmakologie und Toxikologie: Arzneimittelwirkungen verstehen- Medikamente gezielt einsetzen; ein Lehrbuch für Studierende der Medizin, der Pharmazie und der Biowissenschaften, eine Informationsquelle für Ärzte, Apotheker und Gesundheitspolitiker. 2006
17. Other Schatzberg AF, Nemeroff CB. Essentials of Clinical Psychopharmacology. February 10, 2006
18. Journal / agency Bantick RA, Rabiner EA, Hirani E, de Vries MH, Hume SP, Grasby PM. Occupancy of agonist drugs at the 5-HT1A receptor. Neuropsychopharmacology. May 2004. doi:10.1038/sj.npp.1300390 · PMID 14985704
19. Journal / agency Monti JM. Serotonin 5-HT(2A) receptor antagonists in the treatment of insomnia: present status and future prospects. Drugs of Today. March 2010. doi:10.1358/dot.2010.46.3.1437247 · PMID 20467592
20. Journal / agency Salmi P, Ahlenius S. Sedative effects of the dopamine D1 receptor agonist A 68930 on rat open-field behavior. NeuroReport. April 2000. doi:10.1097/00001756-200004270-00025 · PMID 10817605
21. Journal / agency Racz R, Kozell LB, Eshleman AJ, Bloom SH, Wolfrum KM, Schmachtenberg JL, Swanson TL, Ngai J, Schutzer WE, Janowsky A, Abbas AI, Stavitskaya L. Evaluation of the Relationship between Vesicular Monoamine Transporter 2 (VMAT2) Inhibition and Neurologic Adverse Events in Approved Drugs. ACS Pharmacology & Translational Science. 22 December 2025. doi:10.1021/acsptsci.5c00538
22. Journal / agency Geodon- ziprasidone hydrochloride capsule; Geodon- ziprasidone mesylate injection, powder, lyophilized, for solution; Geodon- ziprasidone capsule. January 13, 2025
23. Journal / agency Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. September 2013. doi:10.1016/s0140-6736(13)60733-3 · PMID 23810019
24. Journal / agency Baldassano CF, Ballas C, Datto SM, Kim D, Littman L, O'Reardon J, Rynn MA. Ziprasidone-associated mania: a case series and review of the mechanism. Bipolar Disorders. February 2003. doi:10.1034/j.1399-5618.2003.02258.x · PMID 12656943
25. Journal / agency Keating AM, Aoun SL, Dean CE. Ziprasidone-associated mania: a review and report of 2 additional cases. Clinical Neuropharmacology. 2005. doi:10.1097/01.wnf.0000159952.64640.28 · PMID 15795551
26. Journal / agency Davis R, Risch SC. Ziprasidone induction of hypomania in depression?. The American Journal of Psychiatry. April 2002. doi:10.1176/appi.ajp.159.4.673 · PMID 11925314
27. Journal / agency Tschoner A, Engl J, Rettenbacher M, Edlinger M, Kaser S, Tatarczyk T, Effenberger M, Patsch JR, Fleischhacker WW, Ebenbichler CF. Effects of six second generation antipsychotics on body weight and metabolism - risk assessment and results from a prospective study. Pharmacopsychiatry. January 2009. doi:10.1055/s-0028-1100425 · PMID 19153944
28. Journal / agency Guo JJ, Keck PE, Corey-Lisle PK, Li H, Jiang D, Jang R, L'Italien GJ. Risk of diabetes mellitus associated with atypical antipsychotic use among Medicaid patients with bipolar disorder: a nested case-control study. Pharmacotherapy. January 2007. doi:10.1592/phco.27.1.27 · PMID 17192159
29. Journal / agency Sacher J, Mossaheb N, Spindelegger C, Klein N, Geiss-Granadia T, Sauermann R, Lackner E, Joukhadar C, Müller M, Kasper S. Effects of olanzapine and ziprasidone on glucose tolerance in healthy volunteers. Neuropsychopharmacology. June 2008. doi:10.1038/sj.npp.1301541 · PMID 17712347
30. Journal / agency Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs. 2005. doi:10.2165/00023210-200519001-00001 · PMID 15998156
31. Journal / agency FDA Drug Safety Communication: FDA reporting mental health drug ziprasidone (Geodon) associated with rare but potentially fatal skin reactions. December 11, 2014
32. Other British National Formulary. March 2009
33. Other Haddad P, Dursun S, Deakin B. Adverse Syndromes and Psychiatric Drugs: A Clinical Guide. 2004
34. Journal / agency Moncrieff J. Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse. Acta Psychiatrica Scandinavica. July 2006. doi:10.1111/j.1600-0447.2006.00787.x · PMID 16774655
35. Other Sacchetti E, Vita A, Siracusano A, Fleischhacker W. Adherence to Antipsychotics in Schizophrenia. 2013
36. Other Ziprasidone (Professional Patient Advice)
37. Journal / agency Miceli JJ, Glue P, Alderman J, Wilner K. The effect of food on the absorption of oral ziprasidone. Psychopharmacology Bulletin. 2007. PMID 18007569
38. Journal / agency Sandson NB, Armstrong SC, Cozza KL. An overview of psychotropic drug-drug interactions. Psychosomatics. 2005. doi:10.1176/appi.psy.46.5.464 · PMID 16145193
39. Journal / agency Miceli JJ, Anziano RJ, Robarge L, Hansen RA, Laurent A. The effect of carbamazepine on the steady-state pharmacokinetics of ziprasidone in healthy volunteers. British Journal of Clinical Pharmacology. 2000. doi:10.1046/j.1365-2125.2000.00157.x · PMID 10771457 · PMC2015057
40. Journal / agency Miceli JJ, Smith M, Robarge L, Morse T, Laurent A. The effects of ketoconazole on ziprasidone pharmacokinetics--a placebo-controlled crossover study in healthy volunteers. British Journal of Clinical Pharmacology. 2000. doi:10.1046/j.1365-2125.2000.00156.x · PMID 10771458 · PMC2015056
41. Journal / agency Nicolson SE, Nemeroff CB. Ziprasidone in the treatment of mania in bipolar disorder. Neuropsychiatric Disease and Treatment. December 2007. doi:10.2147/NDT.S794 · PMID 19300617 · PMC2656324
42. Journal / agency Del Casale A, Bonanni L, Bargagna P, Novelli F, Fiaschè F, Paolini M, Forcina F, Anibaldi G, Cortese FN, Iannuccelli A, Adriani B, Brugnoli R, Girardi P, Paris J, Pompili M. Current Clinical Psychopharmacology in Borderline Personality Disorder. Curr Neuropharmacol. 2021. doi:10.2174/1570159X19666210610092958 · PMID 34151763 · PMC8977633
43. Journal / agency Stoffers J, Völlm BA, Rücker G, Timmer A, Huband N, Lieb K. Pharmacological interventions for borderline personality disorder. Cochrane Database Syst Rev. June 2010. doi:10.1002/14651858.CD005653.pub2 · PMID 20556762 · PMC4169794
44. Journal / agency Pascual JC, Soler J, Puigdemont D, Pérez-Egea R, Tiana T, Alvarez E, Pérez V. Ziprasidone in the treatment of borderline personality disorder: a double-blind, placebo-controlled, randomized study. J Clin Psychiatry. April 2008. doi:10.4088/jcp.v69n0412 · PMID 18251623
45. Journal / agency Pascual JC, Oller S, Soler J, Barrachina J, Alvarez E, Pérez V. Ziprasidone in the acute treatment of borderline personality disorder in psychiatric emergency services. J Clin Psychiatry. September 2004. doi:10.4088/jcp.v65n0918b · PMID 15367057
46. Other Lemke TL, Williams DA. Foye's Principles of Medicinal Chemistry. January 24, 2012
47. Journal / agency Farah A. Atypicality of atypical antipsychotics. Primary Care Companion to the Journal of Clinical Psychiatry. 2005. doi:10.4088/pcc.v07n0602 · PMID 16498489 · PMC1324958
48. Other Newcomer JW, Fallucco EM. The American Psychiatric Publishing textbook of psychopharmacology. 2009
49. Journal / agency Approval Package For: Application Number 20-919. May 26, 1998
50. Other First Approval For Pfizer's Zeldoxs
51. Other Pfizer's Zeldox approvable in USA – Pharmaceutical industry news. September 13, 2000
52. Journal / agency PsychoPharmacological Drugs Advisory Committee. FDA Background On ZeldoxTM (ziprasidone hydrochloride capsules) Pfizer, Inc. July 19, 2000
53. Other Pfizer to Launch Zeldox in 9 European Union Countries Beginning Next Month
54. Other Justice Department Announces Largest Health Care Fraud Settlement in Its History. September 2, 2009
55. Other Vella, Vinny. Phoenixville Hospital staff gave man a 'lethal dose' of medication during mental-health crisis, his family says. 17 March 2025
56. Other Pfizer Completes Transaction to Combine Its Upjohn Business with Mylan. November 16, 2020
57. Other Geodon
58. Other Brands. November 16, 2020

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.