Harvey PD, Bowie CR. Ziprasidone: efficacy, tolerability, and emerging data on wide-ranging effectiveness. Expert Opin Pharmacother 6: 337-346

Mt. Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
Expert Opinion on Pharmacotherapy (Impact Factor: 3.53). 03/2005; 6(2):337-46. DOI: 10.1517/14656566.6.2.337
Source: PubMed


Ziprasidone is the fifth atypical antipsychotic to become available in the US market. This compound is a serotonin-dopamine-receptor antagonist, with greater affinity for the 5-HT(2A) receptor than the dopamine D2 receptor. Similar to aripiprazole, this compound also has agonist activity at the serotonin 5-HT(1A) receptor. This affinity has the potential to have particularly beneficial effects on cognitive and affective abnormalities in schizophrenia. Oral and short-acting intramuscular formulations are available. This compound has recently been approved for the treatment of acute mania as well as for schizophrenia. Ziprasidone is associated with low weight gain and a low potential to change lipid and glucose levels. Long-term tolerability data have indicated that initial concerns regarding QTc (corrected cardiac output) prolongation are not a major issue. Recent data have indicated that this compound has short-term antipsychotic efficacy that is equivalent to other members of the class, also with evidence of cognitive enhancement. Finally, longer term data has indicated that ziprasidone is successful in the prevention of relapse and has sustained cognitive benefits. Several issues remain to be addressed, including the efficacy of once-daily dosing, the need to take the medication with food, and the correct dosing strategy.

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    • "Ziprasidone is contraindicated in patients with a known history of QTc prolongation, recent acute myocardial infarction and uncompensated heart failure and to be avoided if the patient is taking agents capable of significantly prolonging QTc interval (pimozide, thioridazine, selected antiarrhythmics, moxifloxacine and sparfloxacine) but EKGs are generally not recommended. 12 All that said, ziprasidone seems to be a very suitable first-line antipsychotic treatment for individuals with no known history of cardiac problems related to arrhythmia or QTc interval and without the need for EKG monitoring.49 "
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    ABSTRACT: Since schizophrenia is considered one of the top ten causes of disease-related disability in the world, the development of second-generation (atypical) antipsychotics (SGAs) has increased the hopes of psychiatrists. SGAs, however, cannot be considered a unique pharmacological class since each SGA has many complex pharmacologic actions, only some of which are shared with other SGAs. Even though manyantipsychotics have similar efficacy on average, prescribers may be able to achieve better than average results by considering differences in selecting a specific drug for a specific patient. Clinicians know that each patient is unique. In order to achieve best outcomes for the individual patient, the better therapy is the therapy tailored for the single patient. With this article, we provide information on a relatively new antipsychotic ziprasidone released in 2001 by Pfizer for the treatment of schizophrenia. Compared with other first line atypical antipsychotics ziprasidone has a unique profile due to potent interaction with serotonergic receptors and lesser action upon α1 adrenergic, H1 and M1 antagonist activities. This paper describes the development of ziprasidone, its unique properties and its metabolically-friendly profile including its receptor binding affinities, pharmacokinetics, CNS activity results of clinical efficacy and relevant clinical trials. Safety, efficacy and patient preference are also examined. The available literature on ziprasidone of the last five years is reviewed.
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    • "followed by olanzapine, and then by risperidone and quetiapine having intermediate effects, and ziprasidone and aripiprazole conferring the lowest risk for weight gain (Newcomer, 2005a, b; Harvey and Bowie, 2005; Dwyer et al, 2001). Obesity can increase the risk of overt diabetes in high-risk individuals, and provides at least a partial explanation for higher rates of diabetes in SGAs-treated patients. "
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    ABSTRACT: Treatment with second-generation antipsychotics (SGAs) has been associated with weight gain and the development of diabetes mellitus, although the mechanisms are unknown. We tested the hypothesis that SGAs exert direct cellular effects on insulin action and substrate metabolism in adipocytes. We utilized two cultured cell models including 3T3-L1 adipocytes and primary cultured rat adipocytes, and tested for effects of SGAs risperidone (RISP), clozapine (CLZ), olanzapine (OLZ), and quetiapine (QUE), together with conventional antipsychotic drugs butyrophenone (BUTY), and trifluoperazine (TFP), over a wide concentration range from 1 to 500 microM. The effects of antipsychotic drugs on basal and insulin-stimulated rates of glucose transport were studied at 3 h, 15 h, and 3 days. Both CLZ and OLZ (but not RISP) at doses as low as 5 microM were able to significantly decrease the maximal insulin-stimulated glucose transport rate by approximately 40% in 3T3-L1 cells, whereas CLZ and RISP reduced insulin-stimulated glucose transport rates in primary cultured rat adipocytes by approximately 50-70%. Conventional drugs (BUTY and TFP) did not affect glucose transport rates. Regarding intracellular glucose metabolism, both SGAs (OLZ, QUE, RISP) and conventional drugs (BUTY and TFP) increased basal and/or insulin-stimulated glucose oxidation rates, whereas rates of lipogenesis were increased by CLZ, OLZ, QUE, and BUTY. Finally, rates of lipolysis in response to isoproterenol were reduced by the SGAs (CLZ, OLZ, QUE, RISP), but not by BUTY or TFP. These experiments demonstrate that antipsychotic drugs can differentially affect insulin action and metabolism through direct cellular effects in adipocytes. However, only SGAs were able to impair the insulin-responsive glucose transport system and to impair lipolysis in adipocytes. Thus, SGAs directly induce insulin resistance and alter lipogenesis and lipolysis in favor of progressive lipid accumulation and adipocyte enlargement. These effects of SGAs on adipocytes could explain, in part, the association of SGAs with weight gain and diabetes.
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    ABSTRACT: Delusional disorder is an uncommon mental illness with an estimated prevalence of 0.03%. Its low prevalence has likely contributed to the paucity of research interest in this area, leading to substantial gaps in knowledge concerning its treatment and management. In the absence of a robust literature, most clinicians rely on their experience and guidelines for treating schizophrenia when treating patients with delusional disorder. This article reviews the available literature that is specific to the treatment of delusional disorder. In addition, it focuses on specific forensic and medicolegal aspects of managing patients with delusional disorder.
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