Ziprasidone Study Guide

Ziprasidone Study Guide

Description

Ziprasidone is an atypical antipsychotic medication approved by the Food and Drug Administration (FDA) for treating schizophrenia and acute bipolar mania. It is a serotonin-dopamine antagonist classified as a second-generation antipsychotic (SGA). It has both dopamine type-2 (D2) and serotonin type-2 (5-HT2) receptor-blocking properties, which allows it to reduce positive and negative symptoms of schizophrenia, as well as agitation and depression (Coralic et al., 2022). Ziprasidone is prescribed to adults, adolescents, and children ten years or older for treating schizophrenia and acute manic or mixed episodes associated with bipolar disorder. It is commonly marketed under the brand name Geodon but is also available in generic form.

Ziprasidone Monograph for Professionals - Drugs.com

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Description of the Psychopharmacological medication agent, including brand and generic names and appropriate FDA indication, uses

Generic Name: Ziprasidone

Brand Name: Geodon

Extracted from: https://www.marylandmalpracticecenter.com/wp-content/uploads/2015/01/geodon.jpg

FDA Indications Uses

Geodon has been approved by the U.S. Food and Drug Administration (FDA) for treating schizophrenia and acute manic or mixed episodes associated with bipolar disorder in adults, adolescents, and children ten years or older.

Non-FDA Uses

● Ziprasidone has been studied as an adjunctive therapy to treat bipolar disorder, schizophrenia, and other psychiatric disorders and as a potential treatment for autism spectrum disorder, Tourette syndrome, and agitation in dementia patients. Results from studies have been mixed but generally suggest that ziprasidone may be beneficial in some cases (Wozniak et al., 2022).

● Studies have suggested that Ziprasidone may also effectively treat major depression as an adjunct therapy to antidepressants. Further randomized placebo-controlled trials are needed to substantiate this use.

● Studies have demonstrated that ziprasidone may effectively treat behavioral disturbances associated with dementia in elderly patients.

● Ziprasidone has also been shown to reduce symptoms of aggression, agitation, and irritability in pediatric patients.

● Also, studies suggest that Ziprasidone may effectively treat anxiety disorders such as social anxiety, panic disorder, and posttraumatic stress disorder (PTSD) (Tashan, Karakucuk, & Celebi, 2019). 

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Research Supporting Non-FDA Uses

A systematic review by Wozniak et al. (2022) found that ziprasidone was significantly better than a placebo in improving depressive symptoms when used as an adjunct to antidepressant treatment. This finding suggests that it may be useful in treating major depression as an adjunct therapy to antidepressants. Another systematic review by Younce, Davis, & Black (2019) found that ziprasidone may effectively treat anxiety disorders such as social anxiety, panic disorder, and PTSD. However, further research is needed to substantiate this finding.

Drug Classification

Ziprasidone is a second-generation antipsychotic belonging to the benzisoxazole class of drugs yet is chemically unrelated to other antipsychotics on the market (Martel et al., 2021).

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The medication mechanism of action

Ziprasidone is an atypical antipsychotic that blocks certain brain receptors, including serotonin, dopamine, and norepinephrine. It is believed to help regulate chemical imbalances in the brain that may be responsible for symptoms of mental disorders like schizophrenia, bipolar disorder, and certain depressive disorders. Ziprasidone works by blocking the action of certain chemicals in the brain called neurotransmitters. It is thought to be due to its ability to block receptors that respond to dopamine and serotonin (Younce, Davis, & Black, 2019). Ziprasidone works by blocking the action of dopamine and other neurotransmitters in the brain. It is believed to work by blocking the reuptake of dopamine and serotonin and inhibiting the action of acetylcholine, histamine, and other neurotransmitters.

Ziprasidone, a second-generation antipsychotic drug, triggers a macrophage inflammatory response in vitro. Extracted from: https://ars.els-cdn.com/content/image/1-s2.0-S1043466617303319-fx1.jpg

The medication pharmacokinetics

Ziprasidone has a long half-life of about 7 hours and is rapidly metabolized by the liver via a series of enzymes. The active metabolites are excreted primarily through the kidneys. Ziprasidone is absorbed quickly in the gastrointestinal tract and is rapidly distributed throughout the body. It has a half-life of approximately 7-8 hours (Tashan, Karakucuk, & Celebi, 2019).

Pharmacodynamics

Ziprasidone is an atypical antipsychotic medication that works by blocking D2 dopamine receptors in the brain and other receptors, including serotonin, histamine, and muscarinic acetylcholine. This action helps to reduce psychotic symptoms such as hallucinations, delusions, and disorganized thinking. The mechanism of action and pharmacodynamics Ziprasidone is a serotonin-dopamine antagonist that works by blocking dopamine type-2 (D2) and serotonin type-2 (5-HT2) receptors in the brain (Martel et al., 2021). This action helps to reduce positive and negative symptoms of schizophrenia, as well as agitation and depression associated with bipolar mania.

Mechanism of Action and Pharmacodynamics of Ziprasidone. Extracted from: https://cdn.psychopharmacologyinstitute.com/wpengine/uploads/2013/11/Ziprasidone.png

Dosing and Administration

Ziprasidone is available as an oral tablet and an intramuscular injection. It is usually taken twice a day with or without food. The dosage and frequency of administration will depend on the individual’s condition and response to the medication. It is important to follow the doctor’s instructions carefully and not to change the dosage or frequency of administration without consulting a healthcare provider. The recommended starting dose of ziprasidone is 20mg twice daily. The maximum recommended daily dose is 160mg per day. It is typically taken orally, usually with or without food (Martel et al., 2021). Depending on individual patient characteristics, such as age, weight, and concurrent medications, there are various considerations for dosing adjustments. Patients should be monitored closely when taking ziprasidone, and any dose alterations should be cautiously made.

Ziprasidone (Geodon) - Drug information. https://emedz.net/blog/wp-content/uploads/2019/09/geodon-ziprasidone.jpg

Appropriate dosing, administration route, and any considerations for dosing alterations

Ziprasidone should be taken orally as immediate-release tablets (20 mg, 40 mg, 60 mg, 80 mg) or capsules (10 mg, 20 mg, 40 mg, 60 mg). The recommended initial dosage for adults is 20 – 40 mg twice daily. Dosage adjustments may be made in 10 – 20 mg increments every one to two days up to a maximum of 80mg twice daily (Khan et al., 2020). The maximum recommended daily dosage is 160mg. - Lower dosages should be initiated in elderly patients, patients with renal impairment, or patients taking other medications that may interact with ziprasidone.

Geodon: Package Insert / Prescribing Information - Drugs.com. Extracted from: https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcS5ibZoQzpXOy5aOditrhaO-SBm7l77mGNAcw&usqp=CAU

Ziprasidone is available as an oral capsule or suspension and may also be administered intramuscularly by a healthcare professional in certain situations. When making dosing adjustments, reduce or increase the dosage in 10-20 mg increments of ziprasidone daily, depending on the patient's clinical response and tolerability of the medication. Considerations for dosing alterations may include age, weight, concomitant medications, and any existing conditions (Khan et al., 2020).

Considerations of use and dosing in specific specialty populations to consider children, adolescents, elderly, pregnancy, suicidal behaviors

Ziprasidone has not been approved for children below 18 years old. Higher dosages are not recommended for elderly patients due to the increased risk of adverse effects such as QT prolongation and bradycardia. Pregnant women should only take ziprasidone if the potential benefit justifies the potential risk to the fetus. The use of ziprasidone in those with suicidal behaviors should be monitored closely due to an increase in suicidality risks with this class of medications (Khan et al., 2020).

Children and adolescents: Ziprasidone is not recommended for use in children and adolescents under 18 due to the possible risk of suicidal thoughts or behaviors.

Elderly: Lower dosages should be initiated in elderly patients, as they may be more sensitive to the effects of ziprasidone.

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Pregnant women: Ziprasidone should be avoided in pregnant women as it may cause significant harm to a developing fetus.

Suicidal behaviors: Ziprasidone is not recommended for use in patients with suicidal thoughts or behaviors due to the possible risk of worsening symptoms (Praveen et al., 2020).

Half-Life

Definition of Half-Life: The half-life is the amount of time it takes for half of the drug to be eliminated from the body. This is important because it determines how long the drug will remain in the body and how often the medication needs to be taken.

Why Half-Life is Important: Half-life is important because it determines how long a medication will remain in the body and how often it needs to be taken. Knowing the half-life of a medication can help healthcare providers adjust the dosage of the medication to ensure the most effective and safe treatment (Praveen et al., 2020).

The half-life for Ziprasidone: The half-life of ziprasidone is 6-10 hours. This means that after 6-10 hours, half of the drug will have been eliminated from the body. Therefore, taking the medication at regular intervals is important to ensure the drug is present in the body in the necessary amounts.

Ziprasidone | C21H21ClN4OS - PubChem. https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?cid=60854&t=l

Side Effects/Adverse Reactions Potential:

Common side effects of ziprasidone include nausea, constipation, headache, anxiety, insomnia, dizziness, restlessness, and blurred vision. Rare side effects include allergic reactions, low blood pressure, and seizures. Long-term use may increase the risk of weight gain, movement disorders, and type 2 diabetes  (Praveen et al., 2020).

Drug Interactions: Ziprasidone can interact with other medications, including anticoagulants, antidepressants, and other antipsychotics. It is important to tell your healthcare provider about all medications and supplements you are taking, including over-the-counter medications. Tell your doctor about all medications you take before using ziprasidone (Khan et al., 2020).

Contraindications: It is contraindicated in individuals allergic to ziprasidone or its components. It should also not be used in patients with a history of low blood pressure, seizures, or a recent heart attack.

Contraindications for Drug to Drug: Ziprasidone is contraindicated in patients with a known hypersensitivity to ziprasidone, with concurrent use of a monoamine oxidase inhibitor (MAOI), or with a history of the neuroleptic malignant syndrome (NMS). It should also not be used in patients with tardive dyskinesia, heart failure, or myocardial infarction (Praveen et al., 2020).

Drug Interactions for Drug to Drug: Ziprasidone may interact with several other medications, including but not limited to: selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, thioridazine, anticholinergic medications, benzodiazepines, antihistamines, and anticonvulsants (Khan et al., 2020).

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Overdose Considerations: Symptoms of an overdose of ziprasidone may include drowsiness, confusion, coma, seizures, and abnormal heart rhythms. In cases of overdose, contact a healthcare provider immediately (Khan et al., 2020).

Additional Considerations: Ziprasidone may cause side effects, including but not limited to dizziness, drowsiness, restlessness, headache, nausea, vomiting, constipation, dry mouth, and weight gain. It may also cause an increase in blood sugar levels and the risk of developing diabetes. It is important to monitor for any changes in mood or behavior when taking ziprasidone. Women should talk to their healthcare provider if they are pregnant or breastfeeding (Støve et al., 2022).

Commonly Reported Adverse Events with Ziprasidone 20,22. Extracted from: https://www.researchgate.net/publication/11391419/figure/tbl4/AS:394420697485317@1471048630482/Commonly-Reported-Adverse-Events-with-Ziprasidone-20-22.png

Diagnostics and Labs Monitoring

● Monitor the patient for signs and symptoms of adverse reactions such as weight gain, movement disorders, and sedation. 

● Monitor for suicidality in high-risk patients. 

● Obtain baseline ECG, CBC, lipid profile, renal and hepatic function, and ophthalmologic examination prior to initiating treatment (Støve, et al., 2022). 

● Monitor fasting blood glucose and glycosylated hemoglobin levels in patients with diabetes. 

● Monitor CBC and metabolic panel at regular intervals during treatment. 

Credit: Recommendations for lab monitoring of atypical antipsychotics | MDedge Psychiatry. https://cdn.mdedge.com/files/s3fs-public/Image/September-2017/RTEmagicC_CP012090051_t2.jpg.jpg

Comorbidities Considerations

● Discontinue treatment in patients with neuroleptic malignant syndrome or NMS-like reactions. 

● Monitor patients with cardiac disease, including congestive heart failure, cardiomyopathy, bradycardia, and conduction abnormalities, and those with risk factors for QT prolongation for signs of arrhythmia. 

● Use with caution in patients with hepatic impairment, as it has not been studied in this population. 

● Use with caution in patients with renal impairment, as it has not been studied in this population  (Biesdorf et al., 2019).

● Use with caution in patients with seizure disorders or a history of seizures. 

● Apply with caution in patients with a history of mania or bipolar disorder.

● Use caution in elderly patients, as they may be more sensitive to the effects of ziprasidone. 

● Use with caution in patients with a history of substance abuse. 

● Use with caution in patients with a history of suicidal ideation or behavior  (Praveen et al., 2020). 

Chart showing the underlying comorbidities. | Download Scientific Diagram. https://www.researchgate.net/publication/327107863/figure/fig2/AS:677104098226176@1538445605229/Chart-showing-the-underlying-comorbidities.png

Legal and Ethical Considerations

● The use of ziprasidone is regulated by the FDA and should be used in accordance with the approved indications.

● The use of ziprasidone is only recommended for patients diagnosed with schizophrenia and bipolar disorder.

● Patients should be informed of the potential side effects of ziprasidone, including weight gain, blurred vision, dizziness, and changes in blood sugar levels. 

● Patients taking ziprasidone should not drive or operate heavy machinery until they know how the medication affects them (Castle et al., 2022).

● It is important to consider the patient’s lifestyle and current medications when prescribing ziprasidone. 

● Patients should be monitored for abnormal behavior or suicidal thoughts while taking ziprasidone (Støve et al., 2022). 

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Pertinent Patient Education Considerations

● Patients should be informed of the potential benefits of taking ziprasidone, including improved mood, anxiety, and concentration. 

● Clients should be aware of the potential side effects of taking ziprasidone, including weight gain, blurred vision, dizziness, and blood sugar levels. 

● Clients should be aware of the potential interactions between ziprasidone and other medications they may be taking and should inform their healthcare provider of any other medications they are taking. 

● Patients should be aware that ziprasidone may increase the risk of suicidal thoughts or behavior and should be monitored for signs of abnormal behavior. 

● Patients should be instructed to take ziprasidone as directed, usually once or twice daily. 

● Patients should be informed of taking ziprasidone regularly to achieve the best results (Biesdorf et al., 2019). 

Conclusion

Ziprasidone is an atypical antipsychotic medication used to treat symptoms of schizophrenia and bipolar disorder. It works by blocking the action of certain chemical messengers in the brain, which helps to reduce symptoms such as hallucinations, delusions, and aggression. Ziprasidone is an effective and safe treatment for certain mental health conditions. It has been studied extensively in clinical trials and is useful in managing symptoms of schizophrenia and bipolar disorder (Coralic et al., 2022). The side effects associated with ziprasidone are usually mild and can be managed well with proper management. It is important to consult with a healthcare provider before starting treatment with ziprasidone, especially with any preexisting medical conditions. Overall, ziprasidone is a promising medication for the management of mental health disorders that can improve a person’s quality of life.

References

Biesdorf, C., Martins, F. S., Sy, S. K., & Diniz, A. (2019). Physiologically‐based pharmacokinetics of ziprasidone in pregnant women. British Journal of Clinical Pharmacology, 85(5), 914-923.https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.13872

Castle, J. W., Butzbach, D. M., Walker, G. S., Lenehan, C. E., Reith, F., Costello, S. P., & Kirkbride, K. P. (2022). In vitro degradation of ziprasidone in whole human blood. Drug Testing and Analysis.https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/dta.3393

Coralic, Z., Rader, E. S., Vinson, D. R., & Wilson, M. P. (2022). Haloperidol versus ziprasidone with concomitant medications and other predictors of physical restraint duration in the emergency department. The Journal of Emergency Medicine, 62(5), 636-647.https://www.sciencedirect.com/science/article/pii/S0736467921010611

Khan, U. A., Parveen, U., Hasan, N., Ahmed, M. Z., Saad, S., Ahmad, F. J., & Jain, G. K. (2020). Parenteral sustained release lipid phase-transition system of ziprasidone: Fabrication and evaluation for schizophrenia therapy. Drug Design, Development, and Therapy, pp. 14, 2237.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294276/

Martel, M. L., Driver, B. E., Miner, J. R., Biros, M. H., & Cole, J. B. (2021). Randomized Double‐blind Trial of Intramuscular Droperidol, Ziprasidone, and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department. Academic Emergency Medicine, 28(4), 421-434.https://onlinelibrary.wiley.com/doi/abs/10.1111/acem.14124

Praveen, S., Gowda, D., Siddaramaiah, H., & Hemalatha, S. (2020). Ziprasidone hydrochloride loaded nanostructured lipid carriers (NLCS) for intranasal delivery: Optimization and in vivo studies. Int. J. Appl. Pharm, pp. 12, 31–41.https://www.researchgate.net/profile/Sivadasu-Praveen/amp

Støve, S. I., Skjevik, Å. A., Teigen, K., & Martinez, A. (2022). Inhibition of VMAT2 by β2-adrenergic agonists, antagonists, and the atypical antipsychotic ziprasidone. Communications Biology, 5(1), 1-14.https://www.nature.com/articles/s42003-022-04121-1

Tashan, E., Karakucuk, A., & Celebi, N. (2019). Optimization and in vitro evaluation of ziprasidone nanosuspensions produced by a top-down approach. Journal of Drug Delivery Science and Technology, 52, 37-45.https://www.sciencedirect.com/science/article/pii/S1773224719300395

Wozniak, J., DiSalvo, M., Farrell, A., Yule, A., Joshi, G., Cook, E., & Biederman, J. (2022). Can pediatric bipolar disorder be successfully treated when comorbid with conduct disorder? A secondary analysis of clinical trials of risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole. Journal of Psychopharmacology, 02698811221087673.https://journals.sagepub.com/doi/abs/10.1177/02698811221087673

Younce, J. R., Davis, A. A., & Black, K. J. (2019). A systematic review and case series of ziprasidone for psychosis in Parkinson’s disease. Journal of Parkinson's Disease, 9(1), 63–71.https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd181448