Ziprasidone

Article Author:
Daniel Bouchette
Article Editor:
Raman Marwaha
Updated:
2/28/2019 11:41:08 AM
PubMed Link:
Ziprasidone

Indications

Ziprasidone is an atypical antipsychotic that is used to treat schizophrenia, bipolar mania, and acute agitation in schizophrenic patients.[1][2][3]

For schizophrenia, studies have shown that ziprasidone was significantly superior to placebo in rate and time of relapse. The efficacy of ziprasidone in bipolar disorder was established, and it also indicated improvement on the manic syndrome subscale that measures symptoms of mania such as mood, insomnia, excessive energy and activity, and overall behavior and ideation. Patients with acute agitation in schizophrenia were measured as well indicating effectiveness short term. Those with long-term risks need to be reevaluated on a patient-by-patient basis.

Mechanism of Action

Ziprasidone is an atypical antipsychotic that has a binding affinity for dopamine, serotonin, and histamine. Regarding treatment for schizophrenia, antagonism against dopamine (D2) and serotonin (5HT2) is favorable. Its efficacy and mechanism of action for treating bipolar disorder is unknown. Because it antagonizes H1 receptors, it can cause somnolence.

Administration

Ziprasidone is administered through multiple routes. It comes in capsule form and can be supplied orally in 20 mg, 40 mg, 60, and 80 mg capsules. Ziprasidone can also be administered as an intramuscular injection.

For treatment of schizophrenia, if given orally, it should be initially given at 20 mg twice per day with meals. That maximum dosage is 160 mg daily, given 80 mg twice per day if indicated. Medication adjustments should occur at no less than two-day intervals as it takes several days to reach steady-state.

For treatment of bipolar mania, ziprasidone should be given initially at a dose of 40 to 80 mg twice per day with meals. On the second day of treatment, the dose should be adjusted from 60 mg to 80 mg twice a day. Dose adjustments should be made every 2 days as needed.

Ziprasidone can be administered intramuscularly for acute agitation in schizophrenia. It is recommended to administer the drug at 10 mg to 20 mg dosing with a maximum dose of 40 mg per day. Dosing is performed as 10 mg every two hours or 20 mg every four hours for a maximum of 40 mg per day.

The injection should only be administered muscularly and should not be given intravenously.  To begin, add 1.2 mL of sterile water into the vial and shake until the drug is fully dissolved. To give a 20 mg dose, draw 1.0 ml of reconstituted solution. For 10 mg of ziprasidone, pull 0.5 ml of reconstituted solution. Whatever is left in the vial should be discarded, as there are no bacteriostatic or preservative agents in the solution.

Adverse Effects

Patients treated with antipsychotic drugs may develop tardive dyskinesia. This condition is characterized by repetitive, involuntary movements such as grimacing of the face with protrusion or twisting of the tongue. This occurs more commonly in senior women; however, do not rely on prevalence rates to detect which patients are most likely to develop this adverse effect. High dosage and longer treatment increase the risk and likely hood that tardive dyskinesia becomes irreversible. If you suspect tardive dyskinesia in a patient, discontinue the drug as there is no treatment currently available to treat this movement disorder.[3][4][5]

Patients undergoing treatment with ziprasidone are also at risk for neuroleptic malignant syndrome. In this syndrome, patients present with muscle rigidity, high fever, autonomic instability (high blood pressure, diaphoresis), and altered mental status. If you suspect patient with neuroleptic malignant syndrome, supportive care is the most important in management. Treatment with bromocriptine, dantrolene, and amantadine, with discontinuation of ziprasidone, may help.

Lastly, hyperglycemia associated with coma, ketoacidosis, or death can occur in rare cases. Patients who have diabetes mellitus should take ziprasidone with caution. These patients should be monitored on a daily basis.

Contraindications

Patients on drugs that prolong QT interval should not be administered ziprasidone. Patients taking other drugs that act on the central nervous system (CNS) should also not be administered the drug due to the effects of ziprasidone on the primary CNS. Many antihypertensive agents may have their effects increased by ziprasidone as well, leading to hypotension. Ziprasidone's dopamine D2 receptor antagonism may counter the therapeutic effect of levodopa and dopamine agonists.[6]

Monitoring

Ziprasidone's elimination is primarily through the liver. It's half-life is seven hours to ten hours. This drug will reach steady state-concentration within one to three days of dosing. Clearing systemically occurs at 7.5 ml/min/kg.[7][8][9]

A minimal amount of ziprasidone is excreted in the urine. 

It carries a possible risk of causing leukopenia, neutropenia, and agranulocytosis; therefore, patients with a history of low white blood cells (WBC) or drug-induced neutropenia/leukopenia should have their complete blood count monitored in the first two months of therapy. If patients have a neutrophil count of less than 1000/mm3, the drug must be discontinued until WBC count has fully recovered.

In the event of an overdose, ensure the patient maintains ventilation, and intubation may be a possibility. Intravenous (IV) access must be done with gastric lavage after intubation if the patient is unconscious. Charcoal can also be used along with a laxative for drug clearance.

As ziprasidone may cause QT-prolongation, and continuous ECG monitoring should be started in case an arrhythmia occurs.

Toxicity

Patients can develop rash based on exposure time to the drug. It was found that the higher the exposure time, the great risk of developing a rash. Patients that experience rash also had signs of systemic illness, which can be treated with antihistamines, steroids, or discontinuation of the drug.

Orthostatic hypertension can also occur in patients. Patients may experience tachycardia, syncope, dizziness, during the first dose titration period due to a1-antagonism. Caution should be exercised in giving ziprasidone to patients with cardiovascular disease and cerebrovascular disease.

It has been determined that a small number of patients may experience seizures with ziprasidone. Therefore, caution should be exercised when dosing ziprasidone in patients with a history of seizures or conditions that can lower the seizure threshold.

The risk of aspiration pneumonia in elderly must be assessed before giving this drug as well as esophageal dysmotility. Antipsychotics, in general, have been associated with both of these conditions, particularly in patients with Alzheimer disease.

Hyperprolactinemia, leading to galactorrhea, gynecomastia, impotence, and amenorrhea is also possible, secondary to the D2 receptor antagonism in ziprasidone, leading to an elevation in prolactin levels.

As ziprasidone also has binding affinity to histamine H1 receptors, the possibility of somnolence can occur. Priapism, body temperature regulation, and suicide can also occur if the appropriate patient and case management are not exercised.

Enhancing Healthcare Team Outcomes

Ziprasidone is a widely used antipsychotic drug. The drug is usually started by a psychiatrist but the followup of patients is usually done by a primary care provider, nurse practitioner, pharmacist or physician assistant. Zipradisone is an effective drug for schizophrenia but it also has a number of side effects that need to be monitored. Healthcare workers should obtain regular ECGs, blood work and assess the patient for any type of movement disorder. Many of these patients also gain weight rapidly and thus they should be urged to exercise and eat a healthy diet. If tardive dyskinesia is suspected, the patient should be referred to the psychiatrist for other treatment options. [10]


References

[1] Younce JR,Davis AA,Black KJ, A Systematic Review and Case Series of Ziprasidone for Psychosis in Parkinson's Disease. Journal of Parkinson's disease. 2018 Nov 21     [PubMed PMID: 30475775]
[2] Shim IH,Bahk WM,Woo YS,Yoon BH, Pharmacological Treatment of Major Depressive Episodes with Mixed Features: A Systematic Review. Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology. 2018 Nov 30     [PubMed PMID: 30466209]
[3] Macaluso M,Preskorn SH, Knowledge of the Pharmacology of Antidepressants and Antipsychotics Yields Results Comparable With Pharmacogenetic Testing. Journal of psychiatric practice. 2018 Nov     [PubMed PMID: 30395549]
[4] Ali SN,Bazzano LA, Hyponatremia in Association With Second-Generation Antipsychotics: A Systematic Review of Case Reports. The Ochsner journal. 2018 Fall     [PubMed PMID: 30275787]
[5] Bark N,Lawson N,Trigoboff E,Varadi R,Grace J,Olympia J,Sindhu N,Watson T,El-Defrawi M,Roy P, Among the Severely Mentally Ill, Who Responds to Ziprasidone? Clinical schizophrenia     [PubMed PMID: 30040474]
[6] Aronow WS,Shamliyan TA, Effects of atypical antipsychotic drugs on QT interval in patients with mental disorders. Annals of translational medicine. 2018 Apr     [PubMed PMID: 29862236]
[7] Mauri MC,Paletta S,Di Pace C,Reggiori A,Cirnigliaro G,Valli I,Altamura AC, Clinical Pharmacokinetics of Atypical Antipsychotics: An Update. Clinical pharmacokinetics. 2018 Jun 19     [PubMed PMID: 29915922]
[8] Urban AE,CubaƂa WJ, Therapeutic drug monitoring of atypical antipsychotics. Psychiatria polska. 2017 Dec 30     [PubMed PMID: 29432503]
[9] Solmi M,Murru A,Pacchiarotti I,Undurraga J,Veronese N,Fornaro M,Stubbs B,Monaco F,Vieta E,Seeman MV,Correll CU,Carvalho AF, Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Therapeutics and clinical risk management. 2017     [PubMed PMID: 28721057]
[10] Martino D,Karnik V,Osland S,Barnes TRE,Pringsheim TM, Movement Disorders Associated With Antipsychotic Medication in People With Schizophrenia: An Overview of Cochrane Reviews and Meta-Analysis. Canadian journal of psychiatry. Revue canadienne de psychiatrie. 2018 Jan 1     [PubMed PMID: 29758999]