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Ziprasidone

January 01, 1970

Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder.[5] It may be used by mouth and by injection into a muscle (IM).[5] The IM form may be used for acute agitation in people with schizophrenia.[5]

Ziprasidone
Clinical data
Trade namesGeodon, Zeldox, Zipwell, other
AHFS/Drugs.comMonograph
MedlinePlusa699062
License data
Pregnancy
category
  • AU: C
Routes of
administration		By mouth, intramuscular injection (IM)
Drug classAtypical antipsychotic
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability60% (oral)[3]
100% (IM)
MetabolismLiver (aldehyde reductase)
Elimination half-life7 to 10 hours[4]
ExcretionUrine and feces
Identifiers
  • 5-{2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl}-6-chloro-1,3-dihydro-2H-indol-2-one
CAS Number
  • 146939-27-7 Y
PubChem CID
  • 60854
IUPHAR/BPS
  • 59
DrugBank
  • DB00246 Y
ChemSpider
  • 54841 Y
UNII
  • 6UKA5VEJ6X
KEGG
  • D08687 Y
ChEBI
  • CHEBI:10119 Y
ChEMBL
  • ChEMBL708 Y
CompTox Dashboard (EPA)
  • DTXSID4023753
ECHA InfoCard100.106.954
Chemical and physical data
FormulaC21H21ClN4OS
Molar mass412.94 g·mol−1
3D model (JSmol)
  • Interactive image
  • O=C1Cc2c(N1)cc(Cl)c(c2)CCN3CCN(CC3)c4nsc5ccccc45
  • 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) Y
  • Key:MVWVFYHBGMAFLY-UHFFFAOYSA-N Y
  (verify)
3D-animation of a ziprasidone molecule.
Ziprasidon Krka brand medicine.
Wikimedia Commons has media related to Ziprasidone.

Common side effects include dizziness, drowsiness, dry mouth, and twitches.[6][7] Although it can also cause weight gain, the risk is much lower than for other atypical antipsychotics.[8] How it works is not entirely clear but is believed to involve effects on serotonin and dopamine in the brain.[5]

Ziprasidone was approved for medical use in the United States in 2001.[5] 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.[9][10]

Medical uses edit

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.[11]

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.[12] 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.[13]

Adverse effects edit

Ziprasidone (and all other second generation antipsychotics (SGAs)) received a black box warning due to increased mortality in elderly patients with dementia-related psychosis.[14]

Sleepiness and headache are very common adverse effects (>10%).[6][7]

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[8]), rashes, fast heart beats, blood pressure falling when standing up quickly, muscle pain, weakness, twitches, dizziness, and anxiety.[6][7] 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.[15]

Ziprasidone is known to trigger mania in some bipolar patients.[16][17][18]

This medication can cause birth defects, according to animal studies, although this side effect has not been confirmed in humans.[14]

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.[19][20][21][22] In fact, in a trial of long term therapy with ziprasidone, overweight patients (BMI > 27) actually had a mean weight loss overall.[14] 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.[23]

Discontinuation edit

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.[24] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[25] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[25] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[25] Symptoms generally resolve after a short period of time.[25]

There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[26] It may also result in reoccurrence of the condition that is being treated.[27] Rarely tardive dyskinesia can occur when the medication is stopped.[25]

Pharmacology edit

Pharmacodynamics edit

See also: Atypical antipsychotic § Pharmacodynamics, and Antipsychotic § Comparison of medications
Ziprasidone[28]
Site Ki (nM) Action Ref
SERTTooltip Serotonin transporter 112 Blocker [28]
NETTooltip Norepinephrine transporter 44 Blocker [28]
DATTooltip Dopamine transporter >10,000 ND [28]
5-HT1A 2.5–76 Partial agonist [29][30][31]
5-HT1B 0.99–4.0 Partial agonist [30][28]
5-HT1D 5.1–9.0 Partial agonist [30][28]
5-HT1E 360–1,279 ND [30][28]
5-HT2A 0.08–1.4 Antagonist [32][29][30]
5-HT2B 27.2 Antagonist [28]
5-HT2C 0.72–13 Antagonist [29]
5-HT3 >10,000 ND [28]
5-HT5A 291 ND [28]
5-HT6 61–76 Antagonist [31][29]
5-HT7 6.0–9.3 Antagonist [28][31][29]
α1A 18 Antagonist [28][31]
α1B 9.0 Antagonist [28]
α2A 160 Antagonist [28][30][31]
α2B 48 Antagonist [28][30][31]
α2C 59–77 Antagonist [28][30][31]
β1 ≥2,570 ND [30][28]
β2 >10,000 ND [30][28]
D1 30–130 ND [28][29]
D2 4.8 Antagonist [33][29][31]
D2L 4.6 Antagonist [30][34]
D2S 4.2 Antagonist [30]
D3 7.2 Antagonist [33][29][30]
D4 0.8–105 Antagonist [33][29][28]
D4.2 28–39 Antagonist [34]
D4.4 14.9 Antagonist [35]
D5 152 ND [28]
H1 15–130 Antagonist [30][29][28]
H2 3,500 ND [28]
H3 >10,000 ND [28]
H4 >10,000 ND [28]
M1 ≥300 ND [36][28][29]
M2 ≥3,000 ND [36][28]
M3 ≥1,300 ND [36][31][28]
M4 ≥1,600 ND [36][28]
M5 ≥1,600 ND [36][28]
σ1 110 ND [30]
σ2 ND ND ND
Opioid >1,000 ND [30]
nAChTooltip Nicotinic acetylcholine receptor >10,000 ND [28]
NMDA
(PCP)		 >10,000 ND [28]
VDCCTooltip Voltage-dependent calcium channel >10,000 ND [28][30]
VGSCTooltip Voltage-gated sodium channel 2,620 ND [30]
hERGTooltip Human Ether-à-go-go-Related Gene 169 Blocker [37]
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.[28]

Correspondence to clinical effects edit

Ziprasidone mostly affects the receptors of dopamine (D2), serotonin (5-HT2A, partially 5-HT1A, 5-HT2C, and 5-HT1D)[3][38][39] and epinephrine/norepinephrine (α1) to a high degree, while of histamine (H1) - moderately.[40][41] It also somewhat inhibits reuptake of serotonin and norepinephrine, though not dopamine.[40][42]

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.[43] 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.[44]; however, its effects on the 5-HT1A receptor may be limited as a study[45] 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.[46][47]

Pharmacokinetics edit

The systemic bioavailability of ziprasidone is 100% when administered intramuscularly and 60% when administered orally without food.[3]

After a single dose intramuscular administration, the peak serum concentration typically occurs at about 60 minutes after the dose is administered, or earlier.[48] 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.

The bioavailability of the drug is reduced by approximately 50% if a meal is not eaten before Ziprasidone ingestion.[14][49]

Ziprasidone is hepatically metabolized by aldehyde oxidase; minor metabolism occurs via cytochrome P450 3A4 (CYP3A4).[50] Medications that induce (e.g. carbamazepine) or inhibit (e.g. ketoconazole) CYP3A4 have been shown to decrease and increase, respectively, blood levels of ziprasidone.[51][52]

Its biological half-life time is 10 hours at doses of 80–120 milligrams.[4]

History edit

Ziprasidone is chemically similar to risperidone,[53] of which it is a structural analogue.[54] It was first synthesized in 1987 at the Pfizer central research campus in Groton, Connecticut.[55]

Phase I trials started in 1995.[56] In 1998 ziprasidone was approved in Sweden.[57][58] 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.[56][59][60]

Society and culture edit

Lawsuit edit

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.[61] Pfizer had illegally promoted Geodon and submitted false claims 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.[citation needed]

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  61. ^ "Justice Department Announces Largest Health Care Fraud Settlement in Its History". justice.gov. September 2, 2009. Retrieved October 6, 2016.

Further reading edit

  • Taylor D (2006). Schizophrenia in Focus. Pharmaceutical Press. p. 123. ISBN 978-0-85369-607-0. Retrieved May 13, 2012.

January 01, 1970
ziprasidone, sold, under, brand, name, geodon, among, others, atypical, antipsychotic, used, treat, schizophrenia, bipolar, disorder, used, mouth, injection, into, muscle, form, used, acute, agitation, people, with, schizophrenia, clinical, datatrade, namesgeo. Ziprasidone sold under the brand name Geodon among others is an atypical antipsychotic used to treat schizophrenia and bipolar disorder 5 It may be used by mouth and by injection into a muscle IM 5 The IM form may be used for acute agitation in people with schizophrenia 5 ZiprasidoneClinical dataTrade namesGeodon Zeldox Zipwell otherAHFS Drugs comMonographMedlinePlusa699062License dataUS DailyMed Ziprasidone US FDA ZiprasidonePregnancycategoryAU CRoutes ofadministrationBy mouth intramuscular injection IM Drug classAtypical antipsychoticATC codeN05AE04 WHO Legal statusLegal statusAU S4 Prescription only BR Class C1 Other controlled substances 2 US WARNING 1 Rx onlyPharmacokinetic dataBioavailability60 oral 3 100 IM MetabolismLiver aldehyde reductase Elimination half life7 to 10 hours 4 ExcretionUrine and fecesIdentifiersIUPAC name 5 2 4 1 2 benzisothiazol 3 yl 1 piperazinyl ethyl 6 chloro 1 3 dihydro 2H indol 2 oneCAS Number146939 27 7 YPubChem CID60854IUPHAR BPS59DrugBankDB00246 YChemSpider54841 YUNII6UKA5VEJ6XKEGGD08687 YChEBICHEBI 10119 YChEMBLChEMBL708 YCompTox Dashboard EPA DTXSID4023753ECHA InfoCard100 106 954Chemical and physical dataFormulaC 21H 21Cl N 4O SMolar mass412 94 g mol 13D model JSmol Interactive imageSMILES O C1Cc2c N1 cc Cl c c2 CCN3CCN CC3 c4nsc5ccccc45InChI 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 YKey MVWVFYHBGMAFLY UHFFFAOYSA N Y verify 3D animation of a ziprasidone molecule Ziprasidon Krka brand medicine Wikimedia Commons has media related to Ziprasidone Common side effects include dizziness drowsiness dry mouth and twitches 6 7 Although it can also cause weight gain the risk is much lower than for other atypical antipsychotics 8 How it works is not entirely clear but is believed to involve effects on serotonin and dopamine in the brain 5 Ziprasidone was approved for medical use in the United States in 2001 5 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 9 10 Contents 1 Medical uses 2 Adverse effects 2 1 Discontinuation 3 Pharmacology 3 1 Pharmacodynamics 3 1 1 Correspondence to clinical effects 3 2 Pharmacokinetics 4 History 5 Society and culture 5 1 Lawsuit 6 References 7 Further readingMedical uses editZiprasidone 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 11 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 12 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 13 Adverse effects editZiprasidone and all other second generation antipsychotics SGAs received a black box warning due to increased mortality in elderly patients with dementia related psychosis 14 Sleepiness and headache are very common adverse effects gt 10 6 7 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 8 rashes fast heart beats blood pressure falling when standing up quickly muscle pain weakness twitches dizziness and anxiety 6 7 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 15 Ziprasidone is known to trigger mania in some bipolar patients 16 17 18 This medication can cause birth defects according to animal studies although this side effect has not been confirmed in humans 14 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 19 20 21 22 In fact in a trial of long term therapy with ziprasidone overweight patients BMI gt 27 actually had a mean weight loss overall 14 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 23 Discontinuation edit The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse 24 Symptoms of withdrawal commonly include nausea vomiting and loss of appetite 25 Other symptoms may include restlessness increased sweating and trouble sleeping 25 Less commonly there may be a feeling of the world spinning numbness or muscle pains 25 Symptoms generally resolve after a short period of time 25 There is tentative evidence that discontinuation of antipsychotics can result in psychosis 26 It may also result in reoccurrence of the condition that is being treated 27 Rarely tardive dyskinesia can occur when the medication is stopped 25 Pharmacology editPharmacodynamics edit See also Atypical antipsychotic Pharmacodynamics and Antipsychotic Comparison of medications Ziprasidone 28 Site Ki nM Action Ref SERTTooltip Serotonin transporter 112 Blocker 28 NETTooltip Norepinephrine transporter 44 Blocker 28 DATTooltip Dopamine transporter gt 10 000 ND 28 5 HT1A 2 5 76 Partial agonist 29 30 31 5 HT1B 0 99 4 0 Partial agonist 30 28 5 HT1D 5 1 9 0 Partial agonist 30 28 5 HT1E 360 1 279 ND 30 28 5 HT2A 0 08 1 4 Antagonist 32 29 30 5 HT2B 27 2 Antagonist 28 5 HT2C 0 72 13 Antagonist 29 5 HT3 gt 10 000 ND 28 5 HT5A 291 ND 28 5 HT6 61 76 Antagonist 31 29 5 HT7 6 0 9 3 Antagonist 28 31 29 a1A 18 Antagonist 28 31 a1B 9 0 Antagonist 28 a2A 160 Antagonist 28 30 31 a2B 48 Antagonist 28 30 31 a2C 59 77 Antagonist 28 30 31 b1 2 570 ND 30 28 b2 gt 10 000 ND 30 28 D1 30 130 ND 28 29 D2 4 8 Antagonist 33 29 31 D2L 4 6 Antagonist 30 34 D2S 4 2 Antagonist 30 D3 7 2 Antagonist 33 29 30 D4 0 8 105 Antagonist 33 29 28 D4 2 28 39 Antagonist 34 D4 4 14 9 Antagonist 35 D5 152 ND 28 H1 15 130 Antagonist 30 29 28 H2 3 500 ND 28 H3 gt 10 000 ND 28 H4 gt 10 000 ND 28 M1 300 ND 36 28 29 M2 3 000 ND 36 28 M3 1 300 ND 36 31 28 M4 1 600 ND 36 28 M5 1 600 ND 36 28 s1 110 ND 30 s2 ND ND ND Opioid gt 1 000 ND 30 nAChTooltip Nicotinic acetylcholine receptor gt 10 000 ND 28 NMDA PCP gt 10 000 ND 28 VDCCTooltip Voltage dependent calcium channel gt 10 000 ND 28 30 VGSCTooltip Voltage gated sodium channel 2 620 ND 30 hERGTooltip Human Ether a go go Related Gene 169 Blocker 37 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 s1 guinea pig opioid rodent NMDA PCP rat VDCC and VGSC 28 Correspondence to clinical effects edit Ziprasidone mostly affects the receptors of dopamine D2 serotonin 5 HT2A partially 5 HT1A 5 HT2C and 5 HT1D 3 38 39 and epinephrine norepinephrine a1 to a high degree while of histamine H1 moderately 40 41 It also somewhat inhibits reuptake of serotonin and norepinephrine though not dopamine 40 42 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 43 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 44 however its effects on the 5 HT1A receptor may be limited as a study 45 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 a1 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 46 47 Pharmacokinetics edit The systemic bioavailability of ziprasidone is 100 when administered intramuscularly and 60 when administered orally without food 3 After a single dose intramuscular administration the peak serum concentration typically occurs at about 60 minutes after the dose is administered or earlier 48 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 The bioavailability of the drug is reduced by approximately 50 if a meal is not eaten before Ziprasidone ingestion 14 49 Ziprasidone is hepatically metabolized by aldehyde oxidase minor metabolism occurs via cytochrome P450 3A4 CYP3A4 50 Medications that induce e g carbamazepine or inhibit e g ketoconazole CYP3A4 have been shown to decrease and increase respectively blood levels of ziprasidone 51 52 Its biological half life time is 10 hours at doses of 80 120 milligrams 4 History editZiprasidone is chemically similar to risperidone 53 of which it is a structural analogue 54 It was first synthesized in 1987 at the Pfizer central research campus in Groton Connecticut 55 Phase I trials started in 1995 56 In 1998 ziprasidone was approved in Sweden 57 58 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 56 59 60 Society and culture editLawsuit edit 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 61 Pfizer had illegally promoted Geodon and submitted false claims 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 citation needed References edit FDA sourced list of all drugs with black box warnings Use Download Full Results and View Query links nctr crs fda gov FDA Retrieved October 22 2023 Anvisa March 31 2023 RDC Nº 784 Listas de Substancias Entorpecentes Psicotropicas Precursoras e Outras sob Controle Especial Collegiate Board Resolution No 784 Lists of Narcotic Psychotropic Precursor and Other Substances under Special Control in Brazilian Portuguese Diario Oficial da Uniao published April 4 2023 Archived from the original on August 3 2023 Retrieved August 16 2023 a b c Mattei C Rapagnani MP Stahl SM 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 a b Nicolson SE Nemeroff CB December 2007 Ziprasidone in the treatment of mania in bipolar disorder Neuropsychiatric Disease and Treatment 3 6 823 834 doi 10 2147 NDT S794 PMC 2656324 PMID 19300617 a b c d e Ziprasidone Monograph for Professionals Drugs com American Society of Health System Pharmacists Retrieved May 8 2019 a b c Product Information Zeldox IM ziprasidone mesilate Australia Therapeutic Goods Administration February 24 2016 a b c Product Information Zeldox ziprasidone hydrochloride Australia Therapeutic Goods Administration February 24 2016 a b FDA Psychopharmacological Drugs Advisory Committee July 19 2000 Briefing Document for Zeldoz Capsules PDF FDA The Top 300 of 2020 ClinCalc Retrieved October 7 2022 Ziprasidone Drug Usage Statistics ClinCalc Retrieved October 7 2022 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 amp Human Svc and of US Dept of Justice Archived from the original on August 30 2012 Retrieved July 4 2012 Leucht S Cipriani A Spineli L Mavridis D Orey D Richter F et al September 2013 Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia a multiple treatments meta analysis Lancet 382 9896 951 962 doi 10 1016 S0140 6736 13 60733 3 PMID 23810019 S2CID 32085212 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 a b c d Geodon Prescribing Information PDF Pfizer Inc Archived from the original PDF on October 17 2005 Retrieved January 26 2009 Leucht S Cipriani A Spineli L Mavridis D Orey D Richter F et al September 2013 Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia a multiple treatments meta analysis Lancet 382 9896 951 962 doi 10 1016 s0140 6736 13 60733 3 PMID 23810019 S2CID 32085212 Baldassano CF Ballas C Datto SM Kim D Littman L O Reardon J Rynn MA February 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 PMID 12656943 Keating AM Aoun SL Dean CE 2005 Ziprasidone associated mania a review and report of 2 additional cases Clinical Neuropharmacology 28 2 83 86 doi 10 1097 01 wnf 0000159952 64640 28 PMID 15795551 Davis R Risch SC April 2002 Ziprasidone induction of hypomania in depression The American Journal of Psychiatry 159 4 673 674 doi 10 1176 appi ajp 159 4 673 PMID 11925314 Tschoner A Engl J Rettenbacher M Edlinger M Kaser S Tatarczyk T et al January 2009 Effects of six second generation antipsychotics on body weight and metabolism risk assessment and results from a prospective study Pharmacopsychiatry 42 1 29 34 doi 10 1055 s 0028 1100425 PMID 19153944 S2CID 43803033 Guo JJ Keck PE Corey Lisle PK Li H Jiang D Jang R L Italien GJ January 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 PMID 17192159 S2CID 22445126 Sacher J Mossaheb N Spindelegger C Klein N Geiss Granadia T Sauermann R et al June 2008 Effects of olanzapine and ziprasidone on glucose tolerance in healthy volunteers Neuropsychopharmacology 33 7 1633 1641 doi 10 1038 sj npp 1301541 PMID 17712347 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 FDA Drug Safety Communication FDA reporting mental health drug ziprasidone Geodon associated with rare but potentially fatal skin reactions FDA December 11 2014 Retrieved December 12 2014 Joint Formulary Committee B 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 a b c d e Haddad P Dursun S Deakin B 2004 Adverse Syndromes and Psychiatric Drugs A Clinical Guide OUP Oxford pp 207 216 ISBN 9780198527480 Moncrieff J July 2006 Does antipsychotic withdrawal provoke psychosis Review of the literature on rapid onset psychosis supersensitivity psychosis and withdrawal related relapse Acta Psychiatrica Scandinavica 114 1 3 13 doi 10 1111 j 1600 0447 2006 00787 x PMID 16774655 S2CID 6267180 Sacchetti E Vita A Siracusano A Fleischhacker W 2013 Adherence to Antipsychotics in Schizophrenia Springer Science amp Business Media p 85 ISBN 9788847026797 a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah Roth BL Driscol J PDSP Ki Database Psychoactive Drug Screening Program PDSP University of North Carolina at Chapel Hill and the United States National Institute of Mental Health Retrieved August 14 2017 a b c d e f g h i j k Schmidt AW Lebel LA Howard HR Zorn SH August 2001 Ziprasidone a novel antipsychotic agent with a unique human receptor binding profile European Journal of Pharmacology 425 3 197 201 doi 10 1016 s0014 2999 01 01188 8 PMID 11513838 a b c d e f g h i j k l m n o p q r Schotte A Janssen PF Gommeren W Luyten WH Van Gompel P Lesage AS et al March 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 a b c d e f g h i Kroeze WK Hufeisen SJ Popadak BA Renock SM Steinberg S Ernsberger P et al March 2003 H1 histamine receptor affinity predicts short term weight gain for typical and atypical antipsychotic drugs Neuropsychopharmacology 28 3 519 526 doi 10 1038 sj npp 1300027 PMID 12629531 Graham JM Coughenour LL Barr BM Rock DL Nikam SS January 2008 1 Aminoindanes as novel motif with potential atypical antipsychotic properties Bioorganic amp Medicinal Chemistry Letters 18 2 489 493 doi 10 1016 j bmcl 2007 11 106 PMID 18160289 a b c Seeman P Tallerico T March 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 Molecular Psychiatry 3 2 123 134 doi 10 1038 sj mp 4000336 PMID 9577836 S2CID 16484752 a b Arnt J Skarsfeldt T February 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 Newman Tancredi A Audinot V Chaput C Verriele L Millan MJ July 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 The Journal of Pharmacology and Experimental Therapeutics 282 1 181 191 PMID 9223553 a b c d e Bymaster FP Felder CC Tzavara E Nomikos GG Calligaro DO Mckinzie DL October 2003 Muscarinic mechanisms of antipsychotic atypicality Progress in Neuro Psychopharmacology amp Biological Psychiatry 27 7 1125 1143 doi 10 1016 j pnpbp 2003 09 008 PMID 14642972 S2CID 28536368 Kongsamut S Kang J Chen XL Roehr J Rampe D August 2002 A comparison of the receptor binding and HERG channel affinities for a series of antipsychotic drugs European Journal of Pharmacology 450 1 37 41 doi 10 1016 s0014 2999 02 02074 5 PMID 12176106 Seeger TF Seymour PA Schmidt AW Zorn SH Schulz DW Lebel LA 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 1 101 113 PMID 7562537 Brunton L 2011 Goodman amp Gilman s The Pharmacological Basis of Therapeutics 12th Edition China McGraw Hill pp 406 410 ISBN 978 0 07 162442 8 a b Akiskal HS Tohen M June 24 2011 Bipolar Psychopharmacotherapy Caring for the Patient John Wiley amp Sons p 209 ISBN 978 1 119 95664 8 Retrieved May 13 2012 Nemeroff CB Lieberman JA Weiden PJ Harvey PD Newcomer JW Schatzberg AF et al November 2005 From clinical research to clinical practice a 4 year review of ziprasidone CNS Spectrums 10 11 Suppl 17 1 20 doi 10 1017 S1092852900019842 PMID 16381088 S2CID 26738197 Tatsumi M Jansen K Blakely RD Richelson E March 1999 Pharmacological profile of neuroleptics at human monoamine transporters European Journal of Pharmacology 368 2 3 277 283 doi 10 1016 S0014 2999 99 00005 9 PMID 10193665 Lullmann H Mohr K 2006 Pharmakologie und Toxikologie Arzneimittelwirkungen verstehen Medikamente gezielt einsetzen ein Lehrbuch fur Studierende der Medizin der Pharmazie und der Biowissenschaften eine Informationsquelle fur Arzte Apotheker und Gesundheitspolitiker Georg Thieme Verlag ISBN 978 3 13 368516 0 Retrieved May 13 2012 Schatzberg AF Nemeroff CB February 10 2006 Essentials of Clinical Psychopharmacology American Psychiatric Pub p 297 ISBN 978 1 58562 243 6 Retrieved May 13 2012 Bantick RA Rabiner EA Hirani E de Vries MH Hume SP Grasby PM May 2004 Occupancy of agonist drugs at the 5 HT1A receptor Neuropsychopharmacology 29 5 847 859 doi 10 1038 sj npp 1300390 PMID 14985704 S2CID 11509050 Monti JM March 2010 Serotonin 5 HT 2A receptor antagonists in the treatment of insomnia present status and future prospects Drugs of Today 46 3 183 193 doi 10 1358 dot 2010 46 3 1437247 PMID 20467592 Salmi P Ahlenius S April 2000 Sedative effects of the dopamine D1 receptor agonist A 68930 on rat open field behavior NeuroReport 11 6 1269 1272 doi 10 1097 00001756 200004270 00025 PMID 10817605 S2CID 35263421 Ziprasidone Professional Patient Advice Drugs com Retrieved February 2 2016 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 Sandson NB Armstrong SC Cozza KL 2005 An overview of psychotropic drug drug interactions Psychosomatics 46 5 464 494 doi 10 1176 appi psy 46 5 464 PMID 16145193 S2CID 21838792 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 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 Lemke TL Williams DA January 24 2012 Foye s Principles of Medicinal Chemistry Lippincott Williams amp Wilkins ISBN 9781609133450 Farah A 2005 Atypicality of atypical antipsychotics Primary Care Companion to the Journal of Clinical Psychiatry 7 6 268 274 doi 10 4088 pcc v07n0602 PMC 1324958 PMID 16498489 Newcomer JW Fallucco EM 2009 Ziprasidone In Schatzberg AF Nemeroff CB eds The American Psychiatric Publishing textbook of psychopharmacology 4th ed Washington D C American Psychiatric Pub p 641 ISBN 9781585623099 a b Approval Package For Application Number 20 919 PDF FDA Center For Drug Evaluation And Research May 26 1998 First Approval For Pfizer s Zeldoxs The Pharma Letter Retrieved October 15 2016 Pfizer s Zeldox approvable in USA Pharmaceutical industry news The Pharma Letter September 13 2000 Retrieved October 15 2016 PsychoPharmacological Drugs Advisory Committee July 19 2000 FDA Background On ZeldoxTM ziprasidone hydrochloride capsules Pfizer Inc PDF Center for Drug Evaluation and Research CDER U S Food and Drug Administration Archived from the original PDF on July 14 2007 Pfizer to Launch Zeldox in 9 European Union Countries Beginning Next Month Pfizer Inc Retrieved October 16 2016 via prnewswire com Justice Department Announces Largest Health Care Fraud Settlement in Its History justice gov September 2 2009 Retrieved October 6 2016 Further reading editTaylor D 2006 Schizophrenia in Focus Pharmaceutical Press p 123 ISBN 978 0 85369 607 0 Retrieved May 13 2012 Retrieved from https en wikipedia org w index php title Ziprasidone amp 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