Antipsychotics ziprasidone

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In recent years, the atypical antipsychotic ziprasidone, which is now also available in oral and injectable forms, has superseded haloperidol as the preferred agent when treating the acutely psychotic and agitated patient with dementia.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. 

Receptor-Binding Studies. Among the newer atypical antipsychotics, ziprasidone (Geodon) has a distinctive pharmacological profile ( Fig. 5-2). Binding studies indicate that ziprasidone has a high affinity for D 2 receptors, approximately equal to that of risperidone. In vitro, ziprasidone ... 

Of the clinically tested new antipsychotics, ziprasidone has the highest 5-HT2A/D2 receptor-affinity ratio. Ziprasidone is an antagonist at the a -adrenoreceptor, but its affinity is half that of its D 2 affinity. In addition, compared with its affinity for D 2 and 5-HT2A receptors, ziprasidone has a relatively low affinity for histamine receptors (pKJ = 7.33). In vitro, ziprasidone is a moderately potent inhibitor of neuronal reuptake of norepinephrine, serotonin, and, to a lesser extent, dopamine. This property is shared with some antidepressants, and contrasts with risperidone, which is inactive at all three monoamine uptake sites. 

Wilner KD, Anziano RJ, Johnson AC, Miceli JJ, Fricke JR, Titus CK. The anxiolytic effect of the novel antipsychotic ziprasidone compared with diazepam in subjects anxious before dental surgery. J Clin Psychopharmacol 2002 22(2) 206-10. 

A search of Medline, EMBASE and PsycLIT was conducted in August 2000, using the following terms Amisulpride, clozapine, olanzapine, risperidone, sertindole, zotepine, ziprasidone, economics, healthcare, costs. All manufacturers of atypical antipsychotic drugs were contacted in April 2000 and asked to supply primary reference data on their product, and all companies had complied with this request by August 2000. A further manual search was conducted of files and journals kept in the National Centre for Information on Psychotropics at the Maudsley Hospital. Reference sections from all retrieved papers were scrutinized for further relevant references. 

Stroup, T. S., Lieberman, J. A., McEvoy, J. P. et al. (2006). Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic. Am. J. Psychiatry, 163, 611-22. 

Current antipsychotics used to treat patients are divided into two classes the first generation antipsychotics (FGA) or typicals (e.g., chlorproma-zine, haloperidol, thioridazine, and loxapine) and the second generation antipsychotics (SGA) or atypicals (i.e., clozapine, olanzapine, quetiapine, risperidone, aripiprazole, ziprasidone, and asenapine). 

Lithium, divalproex sodium (valproate), aripiprazole, olanzapine, que-tiapine, risperidone, and ziprasidone are currently approved by the FDA for treatment of acute mania in bipolar disorder. Lithium, olanzapine, and lamotrigine are approved for maintenance treatment of bipolar disorder. Quetiapine is the only antipsychotic that is FDA approved for bipolar depression. 

Ari pi prazole, olanzapine, quetiapine, risperidone, and ziprasidone are effective as monotherapy or as add-on therapy to lithium or valproate for acute mania. Prophylactic use of antipsychotics can be needed for some patients with recurrent mania or mixed states, but the risks versus benefits must be weighed in view of long-term side effects (e.g., obesity, type 2 diabetes, hyperlipidemia, hyperprolactinemia, cardiac disease, and tardive dyskinesia). 

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. 

IM antipsychotic administration (e.g., ziprasidone 10 to 20 mg, olanzapine 2.5 to 10 mg, or haloperidol 2 to 5 mg) can be used to calm agitated patients. However, this approach does not improve the extent of response, time to remission, or length of hospitalization. 

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... 

C. Prakash, A. Kamel, J. Gummerus, K. Wilner, Metabobsm and Excretion of a New Antipsychotic Drug, Ziprasidone, in Humans , Drug Metab. Dispos. 1997,25, 863 - 872. 

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. 

Choice of a Mood Stabilizer. With the advance of atypical antipsychotics and an ever-expanding list of anticonvulsants, the number of medications reported to treat acute mania and hypomania continues to grow. In fact, all of the atypical antipsychotics, olanzapine, quetiapine, risperidone, ziprasidone, and aripiprazole have FDA approval for the treatment of acute mania. Long-term protection against future episodes of illness has also been demonstrated with several of these agents, which can influence the choice of initial therapy. 

When an antipsychotic is needed, we prefer using one of the newer atypical agents olanzapine, ziprasidone, risperidone, quetiapine, or aripiprazole. Each of these medications reliably reduces agitation and is well tolerated. In particular, they decrease the potential for acute dystonic reactions and tardive dyskinesia caused by the typical antipsychotics. Both ziprasidone and olanzapine are now available in an injectable form that is very rapidly acting and effective in this setting. 

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. 

Among these choices, bnspirone is preferred if the patient is also experiencing anxiety. If the patient is depressed and agitated, a SSRI should be tried first. Second line choices inclnde carbamazepine (Tegretol) or one of the atypical antipsychot-ics—ziprasidone (Geodon), risperidone (Risperdal), olanzapine (Zyprexa), quetiap-ine (Seroquel), or aripiprazole (Abilify) can be tried. If psychotic symptoms are present, one of the atypical antipsychotics should be tried first. 

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... 

The so-called atypical antipsychotics represent one of the newest options for managing disruptive behavioral syndromes. Because they have yet to be studied in patients who have suffered a TBI, we certainly cannot recommend the atypical antipsychotics for routine first-line use. Nevertheless, an atypical antipsychotic might prove helpful when other medicines aren t providing satisfactory results in the management of severe behavioral disturbances. Ziprasidone (Geodon) is available in an injectable form that we have found to be particularly helpful in TBI patients. 

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