Ziprasidone dosing

Mouth and teeth A case of a 52-year-old male who developed severe gingival pain after an increase in ziprasidone dose is reported [288 ]. 

Current or past anti-cholinergic side effects Risperidone, quetiapine, aripiprazole ziprasidone Olanzapine (low dose)... 

Ziprasidone Risperdal Consta Geodon 1, 2, 3, 4 mg Oral solution 1 mg/mL Long-acting injectable 25, 37.5, 50 mg Capsule 20, 40, 60 80 mg 40-160 mg/day in divided doses is not approved at present for bipolar disorder... 

Ziprasidone Geodon Capsule 20, 40,60, 80 mg Calcium channel blockers Not FDA approved for bipolar disorder 40-160 mg/day in divided doses ... 

Most antipsychotics have half-fives of elimination in the range of 20 to 40 hours. After dosage stabilization, most antipsychotics (except quetiapine and ziprasidone) can be dosed once daily. It may be possible to dose SGAs less often than their plasma kinetics would suggest. 

To further illustrate the diversity of hydrolytic opening reactions, we turn our attention to an isothiazole ring as found in the antipsychotic agent ziprasidone (11.129). This drug is subject to various reactions of oxidation and reduction, but also undergoes hydrolytic cleavage of the C=N bond of the isothiazole ring. Evidence for this reaction was afforded by detection of radioactive metabolite 11.130, a sulfonamide, in the urine of patients dosed... 

Quetiapine (Seroquel). Another atypical antipsychotic, quetiapine has also been approved by the FDA for the treatment of acute mania. It is usually administered twice daily at doses of 150-750mg/day. Like its counterparts, quetiapine is a well-tolerated medication. Its common side effects are drowsiness, dizziness, and headache. It causes less weight gain than olanzapine or clozapine but more than ziprasidone or aripiprazole. Quetiapine also does not cause agranulocytosis nor does it increase the risk of seizures. It can occasionally cause mild changes in liver function tests, but these usually return to normal even if the patient continues taking quetiapine. 

Ziprasidone (Geodon). Ziprasidone is indicated for the treatmet of acute mania with typical doses of 40-80 mg twice a day. Ziprasidone is well tolerated, with the most common side effects being sedation, extrapyramidal symptoms, and akathisia. Low magnesium or potassium may cause potentially serious cardiac conduction problems with ziprasidone. 

Injectable ziprasidone, administered in intramuscular doses of 10-20 mg, is now available for managing agitation in the inpatient setting, though it has no routine use in the outpatient setting. A depot formulation of ziprasidone is expected to be approved soon. 

Atypical antipsychotics may be helpful in managing the delusions and agitated behavior that can accompany dementia. These medications, include risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify), and olanzapine (Zyprexa). All antipsychotics, typical and atypical, appear to increase the risk of death in patients with dementia and psychosis. This appears as a warning in the package inserts of the newer drugs. A prudent approach is to discuss this risk with the caregiver, use the lowest effective dose, and monitor for effectiveness. 

Delusions/Psychosis. Demented patients who are acutely psychotic and agitated should be treated in much the same manner as demented patients with delirium. Low doses of a high potency conventional antipsychotic like haloperidol were once preferred. This was mainly because it can be given both orally and by injection. In recent years, the atypical antipsychotic ziprasidone, which is now also available in oral and injectable forms, has superseded haloperidol as the preferred agent when treating the acutely psychotic and agitated patient with dementia. As previously noted, ziprasidone affords the same tranquilizing benefit as haloperidol, it can now be administered via injection when necessary, and it avoids the problematic extrapyramidal symptoms of haloperidol to which patients with dementia are often keenly sensitive. 

We prefer low doses of atypical antipsychotics as a first-line treatment. In this way, the threat of extrapyramidal symptoms is largely avoided without having to use a second anticholinergic medication to offset antipsychotic side effects. Risperidone 0.25-0.5mg/day, olanzapine 2.5mg/day, quetiapine 25mg/day, ziprasidone 20mg/day, or aripiprazole 2.5-5mg/day are reasonable starting doses. The typically higher doses used to treat schizophrenia are usually not necessary. 

Antipsychotics in a few small studies have been shown to be helpful. To date this research is limited to typical antipsychotics. Nevertheless, the excellent track record of atypical antipsychotics in treating schizophrenia and the lower burden of side effects lead us to recommend atypical antipsychotics as a first-line treatment for STPD as well. Low doses of risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole are all reasonable options. If no therapeutic effect is observed, doses should be increased. 

Antipsychotics. Dopamine-blocking antipsychotics can be used to manage the agitation and psychotic symptoms that accompany delirium. Generally, low doses of high potency antipsychotics such as haloperidol have been most often used, though risperidone, ziprasidone, and other atypical antipsychotics are gaining increased acceptance. Because, as we mentioned earlier, some evidence indicates... 

Ziprasidone, pimozide, mesoridazine, and thioridazine have been shown to prolong the QT interval, and drugs with this potential have been associated with torsade de pointes-type arrhythmias and sudden death. Perform a baseline ECG and measure serum potassium and magnesium before initiation of treatment and periodically during treatment, especially during a period of dose adjustment. Patients with QT interval over 450 msec should not receive mesoridazine or thioridazine. Avoid ziprasidone in patients with histories of significant cardiovascular illness (eg. 

Initial treatment Administer ziprasidone capsules at an initial daily dose of 20 mg twice/day with food. In some patients, daily dosage subsequently may be adjusted up to 80 mg twice/day. Dosage adjustments generally should occur at intervals of not less than 2 days. Observe patients for improvement for several weeks before upward dosage adjustment. No additional benefit was demonstrated for doses greater than 20 mg twice/day. 

This group includes risperidone, quetiapine, olanzapine, ziprasidone, and aripiprazole. But all these agents cause dose-related EPS and appear in general more likely to cause diabetes and other metabolic problems than some of the older drugs (see Duggan et ah, 2005). 

Ziprasidone is approved for the treatment of schizophrenia and acute mania. For patients with schizophrenia, ziprasidone is usually started at a dosage of 20-40 mg twice a day. In medically healthy, nonelderly patients, the dose can be rapidly titrated over 2-A days to a typical therapeutic dosage of 60-80 mg twice a day. For patients with acute mania, treatment should be initiated at 40 mg twice... 

Cardiovascular side effects. Ziprasidone produced a mean QTc prolongation of 21 ms at maximal blood levels achieved with typical therapeutic doses. However, in all clinical trials, the rate of QTc intervals greater than 500 ms (considered a threshold for arrhythmia risk) did not differ from the rate associated with placebo (<0.1%). The QTc effect of ziprasidone is larger than that of other atypical antipsychotics but smaller than that of thioridazine. Blood levels of ziprasidone increased about 40% when ketoconazole (a metabolic inhibitor) was coadministered, and no change in QTc duration was detected. 

The time course and proportion of CNS 5-HT2 receptor occupancy by single doses of ziprasidone (40 mg) was determined using the PET ligand [ F]setoperone (133). Serum ziprasidone concentrations ranging from approximately 4 to 125 ng/mL at time points 4 to 18 hours postdose were associated with 5-HT 2 occupancy rates from about 50% to nearly 100%. Receptor occupancy was related to plasma concentration, suggesting that twice daily administration of 20 mg or more to steady-state levels would be expected to provide greater than 80% occupancy of 5-HT 2 receptors. 

Ziprasidone s pharmacokinetics permit rapid and predictable dose adjustment, with metabolites that are considered to be clinically inactive ( 134). The results of PET pharmacokinetic and pharmacodynamic studies indicate that a twice daily dosage regimen is appropriate. 

In one double-blind, randomized, placebo-controlled study, patients were given a daily dose of 40 or 120 mg ziprasidone or placebo for 28 days in 132 patients ( 136). There was a statistically significant improvement in psychotic symptoms versus placebo in the 120 mg/day ziprasidone group as measured by the total BPRS and the CGI scores. Evaluations for parkinsonian symptoms, akathisia, abnormal movements, and sedation did not reveal any notable treatment effects. No significant differences existed between drug and placebo in the total number of adverse events, laboratory test abnormalities, or more serious adverse events. Thus, this study documented that 60 mg ziprasidone twice daily was an effective strategy with negligible risks. 

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