Ziprasidone

Ziprasidone
Names
Trade namesGeodon, Zeldox, Zipwell, other
IUPAC name
  • 5-{2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl}-6-chloro-1,3-dihydro-2H-indol-2-one
Clinical data
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
    Routes of
    use    		By mouth (capsules), intramuscular injection (IM)
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa699062
    Legal
    License data
    Legal status
    • AU: S4 (Prescription only)
    • US: ℞-only
    Pharmacokinetics
    Bioavailability60% (oral)[1]
    100% (IM)
    MetabolismLiver (aldehyde reductase)
    Elimination half-life7 to 10 hours[2]
    ExcretionUrine and feces
    Chemical and physical data
    FormulaC21H21ClN4OS
    Molar mass412.94 g·mol−1
    3D model (JSmol)
    SMILES
    • O=C1Cc2c(N1)cc(Cl)c(c2)CCN3CCN(CC3)c4nsc5ccccc45
    InChI
    • InChI=1S/C21H21ClN4OS/c22-17-13-18-15(12-20(27)23-18)11-14(17)5-6-25-7-9-26(10-8-25)21-16-3-1-2-4-19(16)28-24-21/h1-4,11,13H,5-10,12H2,(H,23,27) checkY
    • Key:MVWVFYHBGMAFLY-UHFFFAOYSA-N checkY

    Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder.[3] It may be used by mouth and by injection into a muscle (IM).[3] The IM form may be used for acute agitation in people with schizophrenia.[3]

    Common side effects include dizziness, drowsiness, dry mouth, and twitches.[4][5] Although it can also cause weight gain, the risk is much lower than for other atypical antipsychotics.[6] How it works is not entirely clear but is believed to involve effects on serotonin and dopamine in the brain.[3]

    Ziprasidone was approved for medical use in the United States in 2001.[3] 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 2017, it was the 261st most commonly prescribed medication in the United States, with more than one million prescriptions.[7][8]

    Medical uses

    Ziprasidone is approved by the U.S. 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.[9]

    In a 2013 study in a comparison of 15 antipsychotic drugs in effectiveness in treating schizophrenic symptoms, ziprasidone demonstrated mild-standard effectiveness. 15% more effective than lurasidone and iloperidone, approximately as effective as chlorpromazine and asenapine, and 9-13% less effective than haloperidol, quetiapine, and aripiprazole.[10] 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.[11]

    Side effects

    Ziprasidone (and all other second generation antipsychotics (SGAs)) received a black box warning due to increased mortality in elderly patients with dementia-related psychosis.[12]

    Sleepiness and headache are very common adverse effects (>10%).[4][5]

    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[6]), rashes, fast heart beats, blood pressure falling when standing up quickly, muscle pain, weakness, twitches, dizziness, and anxiety.[4][5] 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.[13]

    Ziprasidone is known to cause activation into mania in some bipolar patients.[14][15][16]

    This medication can cause birth defects, according to animal studies, although this side effect has not been confirmed in humans.[12]

    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.[17][18][19][20] In fact, in a trial of long term therapy with ziprasidone, overweight patients (BMI > 27) actually had a mean weight loss overall.[12] 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, although this was believed to occur only rarely.[21]

    Discontinuation

    The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.[22] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[23] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[23] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[23] Symptoms generally resolve after a short period of time.[23]

    There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[24] It may also result in reoccurrence of the condition that is being treated.[25] Rarely tardive dyskinesia can occur when the medication is stopped.[23]

    Pharmacology

    Pharmacodynamics

    See also: Atypical antipsychotic § Pharmacodynamics, and Antipsychotic § Comparison of medications
    Ziprasidone[26]
    SiteKi (nM)ActionRef
    SERT112Blocker[26]
    NET44Blocker[26]
    DAT>10,000ND[26]
    5-HT1A2.5–76Partial agonist[27][28][29]
    5-HT1B0.99–4.0Partial agonist[28][26]
    5-HT1D5.1–9.0Partial agonist[28][26]
    5-HT1E360–1,279ND[28][26]
    5-HT2A0.08–1.4Antagonist[30][27][28]
    5-HT2B27.2Antagonist[26]
    5-HT2C0.72–13Partial agonist[27]
    5-HT3>10,000ND[26]
    5-HT5A291ND[26]
    5-HT661–76Antagonist[29][27]
    5-HT76.0–9.3Antagonist[26][29][27]
    α1A18Antagonist[26][29]
    α1B9.0Antagonist[26]
    α2A160Antagonist[26][28][29]
    α2B48Antagonist[26][28][29]
    α2C59–77Antagonist[26][28][29]
    β1≥2,570ND[28][26]
    β2>10,000ND[28][26]
    D130–130ND[26][27]
    D24.8Antagonist[31][27][29]
    D2L4.6Antagonist[28][32]
    D2S4.2Antagonist[28]
    D37.2Antagonist[31][27][28]
    D40.8–105Antagonist[31][27][26]
    D4.228–39Antagonist[32]
    D4.414.9Antagonist[33]
    D5152ND[26]
    H115–130Antagonist[28][27][26]
    H23,500ND[26]
    H3>10,000ND[26]
    H4>10,000ND[26]
    M1≥300ND[34][26][27]
    M2≥3,000ND[34][26]
    M3≥1,300ND[34][29][26]
    M4≥1,600ND[34][26]
    M5≥1,600ND[34][26]
    σ1110ND[28]
    σ2NDNDND
    Opioid>1,000ND[28]
    nACh>10,000ND[26]
    NMDA
    (PCP)    		>10,000ND[26]
    VDCC>10,000ND[26][28]
    VGSC2,620ND[28]
    hERG169Blocker[35]
    Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. All data are for human cloned proteins, except H3 (guinea pig), σ1 (guinea pig), opioid (rodent), NMDA/PCP (rat), VDCC, and VGSC.[26]

    Correspondence to clinical effects

    Ziprasidone mostly affects the receptors of dopamine (D2), serotonin (5-HT2A, partially 5-HT1A, 5-HT2C, and 5-HT1D)[1][36][37] and epinephrine/norepinephrine (α1) to a high degree, while of histamine (H1) - moderately.[38][39] It also somewhat inhibits reuptake of serotonin and norepinephrine, though not dopamine.[38][40]

    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.[41] 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.[42] 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.[43][44]

    Pharmacokinetics

    The systemic bioavailability of ziprasidone is 100% when administered intramuscularly and 60% when administered orally without food.[1]

    After a single dose intramuscular administration, the peak serum concentration typically occurs at about 60 minutes after the dose is administered, or earlier.[45] 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.

    Ziprasidone absorption is optimally achieved when administered with food. Without a meal preceding dose, the bioavailability of the drug is reduced by approximately 50%.[12][46]

    Ziprasidone is hepatically metabolized by aldehyde oxidase; minor metabolism occurs via cytochrome P450 3A4 (CYP3A4).[47] Medications that induce (e.g. carbamazepine) or inhibit (e.g. ketoconazole) CYP3A4 have been shown to decrease and increase, respectively, blood levels of ziprasidone.[48][49]

    Its biological half-life time is 10 hours at doses of 80-120 milligrams.[2]

    History

    Ziprasidone is chemically similar to risperidone,[50] of which it is a structural analogue.[51] It was first synthesized in 1987[52] at the Pfizer central research campus in Groton, Connecticut.[53]

    Phase I trials started in 1995.[54] In 1998 ziprasidone was approved in Sweden.[55][56] 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.[54][57][58]

    Society and culture

    Cost

    The cost of this medication in the U.S. is $103 (USD) for 40 capsule(s) of 20 mg each[59] In 2017, it was the 261st most commonly prescribed medication in the United States, with more than one million prescriptions[7][8]

    • Ziprasidone costs (US)
      Ziprasidone costs (US)
    • Ziprasidone prescriptions (US)
      Ziprasidone prescriptions (US)

    Lawsuit

    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.[60] Pfizer had illegally promoted Geodon and caused false claims to be submitted to government health care programs for uses that were not medically accepted indications. The civil settlement also resolves allegations that Pfizer paid kickbacks to health care providers to induce them to prescribe Geodon, as well as other drugs. This was the largest civil fraud settlement in history against a pharmaceutical company.

    References

    1. 1 2 3 Stahl; Chiara Mattei; Maria Paola Rapagnani (February 2011). "Ziprasidone Hydrocloride: What Role in the Management of Schizophrenia?". Journal of Central Nervous System Disease. 3: 1–16. doi:10.4137/JCNSD.S4138. PMC 3663608. PMID 23861634.
    2. 1 2 Nicolson, SE; Nemeroff, CB (December 2007). "Ziprasidone in the treatment of mania in bipolar disorder". Neuropsychiatr Dis Treat. 3 (6): 823–34. doi:10.2147/NDT.S794. PMC 2656324. PMID 19300617.
    3. 1 2 3 4 5 "Ziprasidone Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on December 27, 2011. Retrieved May 8, 2019.
    4. 1 2 3 "Product Information: Zeldox IM (ziprasidone mesilate)". Australia Therapeutic Goods Administration. February 24, 2016. Archived from the original on July 10, 2017. Retrieved September 29, 2013.
    5. 1 2 3 "Product Information: Zeldox (ziprasidone hydrochloride)". Australia Therapeutic Goods Administration. February 24, 2016. Archived from the original on July 10, 2017. Retrieved October 7, 2016.
    6. 1 2 FDA Psychopharmacological Drugs Advisory Committee (July 19, 2000). "Briefing Document for Zeldoz Capsules" (PDF). FDA. Archived (PDF) from the original on January 19, 2017. Retrieved December 16, 2019.
    7. 1 2 "The Top 300 of 2020". ClinCalc. Archived from the original on March 18, 2020. Retrieved April 11, 2020.
    8. 1 2 "Ziprasidone - Drug Usage Statistics". ClinCalc. Archived from the original on July 8, 2020. Retrieved April 11, 2020.
    9. ↑ "Pfizer to pay $2.3 billion to resolve criminal and civil health care liability relating to fraudulent marketing and the payment of kickbacks". Stop Medicare Fraud, US Dept of Health & Human Svc, and of US Dept of Justice. Archived from the original on August 30, 2012. Retrieved July 4, 2012.
    10. ↑ Leucht, Stefan; Cipriani, Andrea; Spineli, Loukia; Mavridis, Dimitris; Örey, Deniz; Richter, Franziska; Samara, Myrto; Barbui, Corrado; Engel, Rolf R; Geddes, John R; Kissling, Werner; Stapf, Marko Paul; Lässig, Bettina; Salanti, Georgia; Davis, John M (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". The Lancet. 382 (9896): 951–962. doi:10.1016/S0140-6736(13)60733-3. PMID 23810019. S2CID 32085212.
    11. ↑ Citrome, L; Yang, R; Glue, P; Karayal, ON (June 2009). "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. 111 (1–3): 39–45. doi:10.1016/j.schres.2009.03.009. PMID 19375893. S2CID 34910599.
    12. 1 2 3 4 "Geodon Prescribing Information" (PDF). Pfizer, Inc. Archived from the original (PDF) on October 17, 2005. Retrieved January 26, 2009.
    13. ↑ Leucht, Stefan; et al. (2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". The Lancet. 382 (9896): 951–962. doi:10.1016/s0140-6736(13)60733-3. ISSN 0140-6736. PMID 23810019. S2CID 32085212.
    14. ↑ Baldassano, CF; Ballas, C; Datto, SM; et al. (2003). "Ziprasidone-associated mania: a case series and review of the mechanism". Bipolar Disorders. 5 (1): 72–75. doi:10.1034/j.1399-5618.2003.02258.x. ISSN 1398-5647. PMID 12656943.
    15. ↑ Keating AM, Aoun SL, Dean CE (2005). "Ziprasidone-associated mania: a review and report of 2 additional cases". Clinical Neuropharmacology. 28 (2): 83–6. doi:10.1097/01.wnf.0000159952.64640.28. PMID 15795551.
    16. ↑ Davis R, Risch SC (April 2002). "Ziprasidone induction of hypomania in depression?". The American Journal of Psychiatry. 159 (4): 673–4. doi:10.1176/appi.ajp.159.4.673. PMID 11925314. Archived from the original on September 16, 2018. Retrieved May 13, 2012.
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    18. ↑ Guo, Jeff J; Keck, Paul E; Corey-Lisle, Patricia K; et al. (2007). "Risk of Diabetes Mellitus Associated with Atypical Antipsychotic Use Among Medicaid Patients with Bipolar Disorder: A Nested Case-Control Study". Pharmacotherapy. 27 (1): 27–35. CiteSeerX 10.1.1.453.7866. doi:10.1592/phco.27.1.27. ISSN 0277-0008. PMID 17192159. S2CID 22445126.
    19. ↑ Sacher, Julia; Mossaheb, Nilufar; Spindelegger, Christoph; et al. (August 22, 2007). "Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers". Neuropsychopharmacology. 33 (7): 1633–1641. doi:10.1038/sj.npp.1301541. ISSN 0893-133X. PMID 17712347.
    20. ↑ Newcomer JW (2005). "Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review". CNS Drugs. 19 Suppl 1: 1–93. doi:10.2165/00023210-200519001-00001. PMID 15998156. S2CID 36435377.
    21. ↑ "FDA Drug Safety Communication: FDA reporting mental health drug ziprasidone (Geodon) associated with rare but potentially fatal skin reactions". FDA. December 11, 2014. Archived from the original on December 13, 2014. Retrieved December 12, 2014.
    22. ↑ Joint Formulary Committee, BMJ, ed. (March 2009). "4.2.1". British National Formulary (57 ed.). United Kingdom: Royal Pharmaceutical Society of Great Britain. p. 192. ISBN 978-0-85369-845-6. Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.
    23. 1 2 3 4 5 Haddad, Peter; Haddad, Peter M.; Dursun, Serdar; Deakin, Bill (2004). Adverse Syndromes and Psychiatric Drugs: A Clinical Guide. OUP Oxford. p. 207–216. ISBN 9780198527480. Archived from the original on April 14, 2021. Retrieved May 29, 2020.
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    25. ↑ Sacchetti, Emilio; Vita, Antonio; Siracusano, Alberto; Fleischhacker, Wolfgang (2013). Adherence to Antipsychotics in Schizophrenia. Springer Science & Business Media. p. 85. ISBN 9788847026797. Archived from the original on April 14, 2021. Retrieved May 29, 2020.
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    28. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE (1996). "Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding". Psychopharmacology. 124 (1–2): 57–73. doi:10.1007/bf02245606. PMID 8935801. S2CID 12028979.
    29. 1 2 3 4 5 6 7 8 9 Kroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P, Jayathilake K, Meltzer HY, Roth BL (2003). "H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs". Neuropsychopharmacology. 28 (3): 519–26. doi:10.1038/sj.npp.1300027. PMID 12629531.
    30. ↑ Graham JM, Coughenour LL, Barr BM, Rock DL, Nikam SS (2008). "1-Aminoindanes as novel motif with potential atypical antipsychotic properties". Bioorg. Med. Chem. Lett. 18 (2): 489–93. doi:10.1016/j.bmcl.2007.11.106. PMID 18160289.
    31. 1 2 3 Seeman P, Tallerico T (1998). "Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors". Mol. Psychiatry. 3 (2): 123–34. doi:10.1038/sj.mp.4000336. PMID 9577836.
    32. 1 2 Arnt J, Skarsfeldt T (1998). "Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence". Neuropsychopharmacology. 18 (2): 63–101. doi:10.1016/S0893-133X(97)00112-7. PMID 9430133.
    33. ↑ Newman-Tancredi A, Audinot V, Chaput C, Verrièle L, Millan MJ (1997). "[35S]Guanosine-5'-O-(3-thio)triphosphate binding as a measure of efficacy at human recombinant dopamine D4.4 receptors: actions of antiparkinsonian and antipsychotic agents". J. Pharmacol. Exp. Ther. 282 (1): 181–91. PMID 9223553.
    34. 1 2 3 4 5 Bymaster FP, Felder CC, Tzavara E, Nomikos GG, Calligaro DO, Mckinzie DL (2003). "Muscarinic mechanisms of antipsychotic atypicality". Prog. Neuropsychopharmacol. Biol. Psychiatry. 27 (7): 1125–43. doi:10.1016/j.pnpbp.2003.09.008. PMID 14642972. S2CID 28536368.
    35. ↑ Kongsamut S, Kang J, Chen XL, Roehr J, Rampe D (2002). "A comparison of the receptor binding and HERG channel affinities for a series of antipsychotic drugs". Eur. J. Pharmacol. 450 (1): 37–41. doi:10.1016/s0014-2999(02)02074-5. PMID 12176106.
    36. ↑ Seeger TF, Seymour PA, Schmidt AW, et al. (October 1995). "Ziprasidone (CP-88,059): a new antipsychotic with combined dopamine and serotonin receptor antagonist activity". The Journal of Pharmacology and Experimental Therapeutics. 275 (1): 101–13. PMID 7562537. Archived from the original on August 27, 2021. Retrieved May 13, 2012.
    37. ↑ Brunton, Laurence (2011). Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th Edition. China: McGraw-Hill. pp. 406–410. ISBN 978-0-07-162442-8.
    38. 1 2 Hagop S. Akiskal; Mauricio Tohen (June 24, 2011). Bipolar Psychopharmacotherapy: Caring for the Patient. John Wiley & Sons. p. 209. ISBN 978-1-119-95664-8. Archived from the original on July 5, 2014. Retrieved May 13, 2012.
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    40. ↑ Tatsumi M, Jansen K, Blakely RD, Richelson E (March 1999). "Pharmacological profile of neuroleptics at human monoamine transporters". European Journal of Pharmacology. 368 (2–3): 277–83. doi:10.1016/S0014-2999(99)00005-9. PMID 10193665.
    41. ↑ Heinz Lüllmann; Klaus Mohr (2006). 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. Georg Thieme Verlag. ISBN 978-3-13-368516-0. Archived from the original on August 27, 2021. Retrieved May 13, 2012.
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    45. ↑ "Ziprasidone (Professional Patient Advice)". Drugs.com. Archived from the original on September 27, 2017. Retrieved February 2, 2016.
    46. ↑ Miceli JJ, Glue P, Alderman J, Wilner K (2007). "The effect of food on the absorption of oral ziprasidone". Psychopharmacology Bulletin. 40 (3): 58–68. PMID 18007569.
    47. ↑ Sandson NB, Armstrong SC, Cozza KL (2005). "An overview of psychotropic drug-drug interactions". Psychosomatics. 46 (5): 464–94. doi:10.1176/appi.psy.46.5.464. PMID 16145193. S2CID 21838792. Archived from the original on August 27, 2021. Retrieved November 29, 2019.
    48. ↑ Miceli JJ, Anziano RJ, Robarge L, Hansen RA, Laurent A (2000). "The effect of carbamazepine on the steady-state pharmacokinetics of ziprasidone in healthy volunteers". British Journal of Clinical Pharmacology. 49 Suppl 1: 65S–70S. doi:10.1046/j.1365-2125.2000.00157.x. PMC 2015057. PMID 10771457.
    49. ↑ Miceli JJ, Smith M, Robarge L, Morse T, Laurent A (2000). "The effects of ketoconazole on ziprasidone pharmacokinetics—a placebo-controlled crossover study in healthy volunteers". British Journal of Clinical Pharmacology. 49 Suppl 1: 71S–76S. doi:10.1046/j.1365-2125.2000.00156.x. PMC 2015056. PMID 10771458.
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    53. ↑ Newcomer, John W.; Fallucco, Elise M. (2009). "Ziprasidone". In Schatzberg, Alan F.; Nemeroff, Charles B. (eds.). The American Psychiatric Publishing textbook of psychopharmacology (4th ed.). Washington, D.C.: American Psychiatric Pub. p. 641. ISBN 9781585623099. Archived from the original on August 27, 2021. Retrieved November 6, 2016.
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