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Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic that is used for the treatment of schizophrenia as well as acute mania and mixed states associated with bipolar disorder.
Common side effects include dizziness, drowsiness, dry mouth, and twitches.
The by mouth form of ziprasidone is the hydrochloride salt, ziprasidone hydrochloride. The intramuscular form is the mesylate rather than hydrochloride salt, ziprasidone mesylate trihydrate, and is provided as a lyophilized powder. Ziprasidone gained approval in the United States on February 5, 2001.
1 Medical uses
2 Adverse effects
3.1.1 Correspondence to clinical effects
5 Society and culture
7 Further reading
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.
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.
Ziprasidone (and all other second generation antipsychotics (SGAs) received a black box warning due to increased mortality in elderly patients with dementia -related psychosis.
Sleepiness and headache are very common adverse effects (>10%).
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
Ziprasidone is known to cause activation into mania in some bipolar patients.
This medication can cause birth defects, according to animal studies, although this side effect has not been confirmed in humans.
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 Zyprexa. Weight gain is also less of a concern with Ziprasidone compared to other atypical antipsychotics. 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.
The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotic treatment to avoid acute withdrawal syndrome or rapid relapse.
See also: Atypical antipsychotic § Pharmacodynamics, and Antipsychotic § Comparison of medications
K i (nM)
NMDA ( PCP )
Values are K i (nM). The smaller the value, the more strongly the drug binds to the site. All data are for human cloned proteins, except H 3 (guinea pig), σ 1 (guinea pig), opioid (rodent), NMDA / PCP (rat), VDCC, and VGSC.
Ziprasidone is a full antagonist of D 2 receptors and of 5-HT 2A receptors and is a partial agonist of 5-HT 1A receptors, of 5-HT 2C receptors and 5-HT 1D receptors.
Correspondence to clinical effects
Ziprasidone’s affinities for most of the dopamine and serotonin receptors and the α 1 -adrenergic receptor are high and its affinity for the histamine H 1 receptor is moderate.
Ziprasidone’s efficacy in treating the positive symptoms of schizophrenia is believed to be mediated primarily via antagonism of the dopamine receptors, specifically D 2. Blockade of the 5-HT 2A 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.
The systemic bioavailability of ziprasidone is 100% when administered intramuscularly and 60% when administered orally without food.
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.
Ziprasidone absorption is optimally achieved when administered with food. Without a meal preceding dose, the bioavailability of the drug is reduced by approximately 50%.
Ziprasidone is hepatically metabolized by aldehyde oxidase ; minor metabolism occurs via cytochrome P450 3A4 (CYP3A4).
Its biological half-life time is 10 hours at doses of 80-120 milligrams.
Ziprasidone is a structural analogue of Risperidone.
Phase I trials started in 1995.
Society and culture
In September 2009, the U.S. Justice Department announced that Pfizer had been ordered to pay an historic fine of $2.3 billion as a penalty for fraudulent marketing of several drugs, including Geodon. 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.
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