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Ziprasidone

Ziprasidone

Definition

Purpose

Description

Recommended dosage

Precautions

Side effects

Interactions

Resources

Definition

Ziprasidone is an atypical antipsychotic drug used to treat schizophrenia. It is available with a prescription under the brand name Geodan.

Purpose

Ziprasidone is in a class of drugs called antipsychotics. It is used to control symptoms of schizophrenia. Ziprasidone is one of the newer antipsychotic drugs—often called atypical antipsychotics—that is less likely to cause significant adverse side effects than conventional antipsychotic medications.

Description

The Food and Drug Administration of the United States approved ziprasidone for treatment of schizophrenia in 2001. In people with schizophrenia, chemical systems in the brain are out of balance. Mental well-being is partially related to maintaining a balance between naturally occurring chemicals called neurotransmitters. Ziprasidone is thought to modify the actions of several neurotransmitters and in this way restore appropriate function to the chemical systems.

Recently, the effectiveness of ziprasidone was evaluated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Study. This study evaluated the effectiveness and side effects of several atypical antipsychotics, including ziprasidone, in comparison to a conventional antipsychotic drug for the treatment of schizophrenia. In Phase 1 of the study it was found that the newer antipsychotic medications—including ziprasidone—were not significantly more effective than the less expensive, conventional antipsychotic medications. In addition, only 23% of participants taking ziprasidone in Phase 1 of the study were able to continue throughout the entire 18 months. Participants who stopped taking their anti-psychotic medication in Phase 1 because it was not adequately controlling their symptoms were more likely to stay on their medication if they were switched to olanzapine or risperidone rather ziprasidone. There was no difference between the four medications tested in Phase 2, however, for participants who had stopped taking their Phase 1 medication because they experienced adverse side effects.

The CATIE study results showed that clozapine is often a good choice of medication for patients who did not respond well to other antipsychotic medications. For patients whose symptoms are not well- controlled on clozapine, however, olanzapine and risperidone tend to be more effective than ziprasidone. Although some of the atypical antipsychotics had significant side effects, including weight gain and metabolic problems, ziprasidone consistently resulted in weight loss and improvement of metabolic disorders. However, of the drugs tested in the CATIE study, risperidone had the least adverse side effects.

Recommended dosage

The dosage of ziprasidone varies widely from one individual to another. A common initially dosage is 20 mg of ziprasidone taken twice daily. The dosage is gradually increased until symptoms of schizophrenia subside. Dosages of up to 100 mg may be taken twice daily. Ziprasidone should be taken with food.

Precautions

Ziprasidone may alter the rhythm of the heart. Because of the risk of irregular heartbeats or even death, it should not be taken by people with a history of irregular or prolonged heart rhythms (long QT syndrome), those with heart failure, or individuals who have recently had a heart attack. People with a history of heart disease should discuss the risks and benefits of treatment with their doctor before starting ziprasidone. Ziprasidone may lower blood pressure to dangerously low levels, causing people to faint. It should not be taken by people who have slow heartbeats and those with low levels of potassium or magnesium in their blood.

Individuals with a history of seizure, even seizure brought on by drug or alcohol abuse, should use ziprasidone cautiously and with close physician supervision, because it may increase the tendency to have seizures.

Ziprasidone may increase body temperatures to dangerously high levels. People who exercise strenuously, those exposed to extreme heat, individuals taking drugs with anticholinergic effects (this includes many common antidepressants ), and persons prone to dehydration, should use the drug cautiously and be alert to dehydration-related side effects. Elderly persons with increased risk of developing pneumonia should be carefully monitored while taking ziprasidone. Because there is a high incidence of suicide in all patients with psychotic illnesses, people using ziprasidone should be observed carefully for signs of suicidal behavior. Women who are pregnant or breastfeeding should not take ziprasidone.

Side effects

The most common reason that ziprasidone is stopped is the development of a rash. Another common side effect is drowsiness. This side effect is usually worse when starting the drug and becomes less severe with continued use. People performing tasks that require mental alertness such as driving or operating machinery should refrain from doing so until they see how the drug affects them. Other side effects that may occur are abnormal, involuntary twitching, (5%), and respiratory disorders (8%). Nausea, constipation, indigestion, and dizziness due to low blood pressure occur in more than 5% of people taking ziprasidone.

Other, less common, side effects are rapid heartbeats, low blood pressure, agitation, tremor, confusion, amnesia, dry mouth, increased salivation, joint pains, and abnormal vision.

The incidence of some adverse effects such as low blood pressure, anorexia, abnormal involuntary movements, sleepiness, tremor, cold symptoms, rash,

KEY TERMS

Anticholinergic —Related to the ability of a drug to block the nervous system chemical called acetyl-choline. When acetylcholine is blocked, patients often experience dry mouth and skin, increased heart rate, blurred vision, and difficulty in urinating. In severe cases, blocking acetylcholine may cloud thinking and cause delirium.

Atypical antipsychotic —A newer antipsychotic drug that is less likely to cause significant adverse side effects than conventional antipsychotic medications. Atypical antipsychotics are also called novel antipsychotics or second-generation antipsychotics.

Milligram (mg) —One-thousandth of a gram. A gram is the metric measure that equals about 0.035 ounces.

Neurotransmitter —A chemical in the brain that transmits messages between neurons, or nerve cells.

Schizophrenia —A severe mental illness in which a person has difficulty distinguishing what is real from what is not real. It is often characterized by hallucinations, delusions, language and communication disturbances, and withdrawal from people and social activities.

abnormal vision, dry mouth or increased salivation appears to increase at higher dosages.

People taking ziprasidone should alert their health care provider immediately if they develop a rash or hives since this could indicate a potentially serious adverse reaction. Patients should also notify their health care provider right away if they experience any abnormal involuntary muscle movements. People who think they may be experiencing side effects from this or any other medication should tell their physicians.

Interactions

Ziprasidone interacts with many other drugs. It is a good idea to review with a physician or pharmacist all medications being taken before starting this drug. Since ziprasidone may alter the rhythm of the heart, people who are taking drugs such as quinidine, dofe-tilide, pimozide, sotalol, erythromycin, thioridazine, moxifloxacin, and sparfloxacin should not take it. These drugs may also affect properties of the heart and taken with ziprasidone increase the risk of irregular heart rhythms and other cardiac problems. Because ziprasidone causes sleepiness, it should be used sparingly and with care with other drugs that also have a tendency to make people drowsy such as antidepressants, antihistamines, some pain relievers, and alcohol. Ziprasidone may lower blood pressure to the point at which people feel dizzy or faint. People taking medication to regulate their blood pressure should have their blood pressure monitored and treatment modified as needed. Ziprasidone may also decrease the effects of drugs used to treat Parkinson’s disease such as levodopa.

Other drugs taken in combination with ziprasidone may alter the effects of ziprasidone. For example, drugs such as carbamazepine, used to treat seizures, increases liver metabolism and may cause ziprasidone to be less effective. Alternatively, drugs such as keto-conazole slow liver metabolism and may increase negative side effects associated with ziprasidone.

Resources

BOOKS

Facts and Comparisons Staff. Drug Facts and Comparisons, 6th ed. St. Louis: Facts and Comparisons, 2002.

Pfizer Staff. Geodan Package Insert. New York: Pfizer Inc., 2001.

Preston, John D., John H. O’Neal, and Mary C. Talaga. Handbook of Clinical Psychopharmacology for Therapists, 4th ed. Oakland, CA: New Harbinger Publications, 2004.

Simpson, George M., Antony Loebel, Lewis Warrington, and Ruoyong Yang. “Efficacy and Tolerability of Ziprasidone and Olanzapine in Acutely Ill Inpatients with Schizophrenia or Schizoaffective Disorder: Results of a Double-Blind, Six-Week Study, with a Six-Month, Double-Blind, Continuation Phase.” Progress in Neurotherapeutics and Neuropsychopharmacology. New York: Cambridge University Press, 2006. 149–63.

PERIODICALS

Barak, Yoram, Doron Mazeh, Igor Plopski, and Yehuda Baruch. “Intramuscular Ziprasidone Treatment of Acute Psychotic Agitation in Elderly Patients with Schizophrenia.” American Journal of Geriatric Psychiatry 14.7 (July 2006): 629–33.

Casey, Daniel E. “Implications of the CATIE Trial on Treatment: Extrapyramidal Symptoms.” CNS Spectrums 11.7 (July 2006): 25–31.

Frederickson, Anne M., John M. Kane, and Peter Manu. “Does Antipsychotic Polypharmacy Increase the Risk For Metabolic Syndrome?” Schizophrenia Research 89.1–3 (Jan. 2007): 91–100.

Gentile, Salvatore. “Extrapyramidal Adverse Events Associated With Atypical Antipsychotic Treatment of Bipolar Disorder.” Journal of Clinical Psychopharmacology 27.1 (Feb. 2007): 35–45.

Ginsberg, David L. “Ziprasidone-Induced Torsade de Pointes.” Primary Psychiatry 13.8 (Aug 2006): 27–29.

Glick, Ira D. “Understanding the Results of CATIE in the Context of the Field.” CNS Spectrums 11.7 (July 2006): 40–47.

Harvey, Philip D., Christopher R. Bowie, and Antony Loe-bel. “Neuropsychological Normalization with Long-Term Atypical Antipsychotic Treatment: Results of a Six-Month Randomized, Double-Blind Comparison of Ziprasidone vs. Olanzapine.” Journal of Neuropsychiatry and Clinical Neurosciences 18.1 (Winter 2006): 54–63.

Joyce, Amie T., and others. “Effect of Initial Ziprasidone Dose on Length of Therapy in Schizophrenia.” Schizophrenia Research 83.2–3 (Apr. 2006): 285–92.

Kane, John M., Sumant Khanna, Sunita Rajadhyaksha, and Earl Giller. “Efficacy and Tolerability of Ziprasidone in Patients with Treatment-Resistant Schizophrenia.” International Clinical Psychopharmacology 21.1 (Jan. 2006): 21–28.

Kinon, Bruce J., Ilya Lipkovich, S. Beth Edwards, David H. Adams, Haya Ascher-Svanum, and Samuel G. Siris “A 24-Week Randomized Study of Olanzapine Versus Ziprasidone in the Treatment of Schizophrenia or Schizoaffective Disorder in Patients with Prominent Depressive Symptoms.” Journal of Clinical Psycho-pharmacology 26.2 (Apr. 2006): 157–62.

Malhotra, Anil K., Katherine E. Burdick, Kamran Razi, John A. Bates, Michael Sanders, and John M. Kane. “Ziprasidone-Induced Cognitive Enhancement in Schizophrenia: Specificity or Pseudospecificity?” Schizophrenia Research 87.1–3) (Oct. 2006): 181–84.

Meltzer, Herbert Y. and William V. Bobo. “Interpreting the Efficacy Findings in the CATIE Study: What Clinicians Should Know.” CNS Spectrums 11.7 (July 2006): 14–24.

Möller, Hans-Jürgen. “Are the New Antipsychotics No Better Than the Classical Neuroleptics? The Problematic Answer from the CATIE Study.” European Archives of Psychiatry and Clinical Neuroscience 255.6 (Dec. 2005): 371–72.

Nasrallah, Henry A. “Metabolic Findings from the CATIE Trial and Their Relation to Tolerability.” CNS Spectrums 11.7 (July 2006): 32–39.

Stroup, T. Scott, and others. “Effectiveness of Olanzapine, Quetiapine, Risperidone, and Ziprasidone in Patients with Chronic Schizophrenia Following Discontinuation of a Previous Atypical Antipsychotic.” American Journal of Psychiatry 163.4 (Apr. 2006): 611–22.

Ziegenbein, Marc and Iris T. Calliess. “Clozapine and Ziprasidone: A Useful Combination in Patients With Treatment-Resistant Schizophrenia.” Journal of Neuropsychiatry and Clinical Neurosciences 18.2 (Spring 2006): 246–47.

Kelly Karpa, R.Ph., PhD

Ruth A. Wienclaw, PhD

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