Disease relevance of Ziprasidone

• CONCLUSIONS: Ziprasidone and olanzapine had comparable long-term efficacy; olanzapine was associated with significant weight gain and metabolic alterations [1].
• Ziprasidone does prolong the QT interval, but there is no evidence to suggest that this leads to torsade de pointes or sudden death [2].
• Ziprasidone-related tardive dyskinesia [3].
• Ziprasidone alternative for olanzapine-induced hyperglycemia [4].
• Parkinsonism with intramuscular ziprasidone [5].

Psychiatry related information on Ziprasidone

• OBJECTIVE: The authors' goal was to compare the efficacy and tolerability of 6 months' treatment with flexible-dose ziprasidone and olanzapine in patients with schizophrenia or schizoaffective disorder [1].
• Sudden akathisia after a ziprasidone dose reduction [6].
• METHOD: Brief Psychiatric Rating Scale (BPRS) scores and Clinical Global Impression (CGI) severity scores were obtained for 126 responders to a 6-week acute study of olanzapine and ziprasidone during a blinded 6-month continuation study and optional extension study [1].
• CONCLUSIONS: Olanzapine treatment resulted in significantly greater psychopathology improvement and higher response and completion rates than ziprasidone treatment, while ziprasidone was superior for weight change and lipid profile [7].
• Ziprasidone-induced acute dystonic reactions in patients with bipolar disorder [8].
• Ziprasidone is an effective treatment for hostility in patients with schizophrenia or schizoaffective disorder [9].

High impact information on Ziprasidone

• RESULTS: The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months) [10].
• Ziprasidone-induced acute dystonia [11].
• Prolactin elevation with ziprasidone [12].
• Specific recommendations were made for cardiac monitoring of patients who receive medications associated with QT interval prolongation, including thioridazine, mesoridazine, and ziprasidone, and for monitoring for signs of myocarditis in patients treated with clozapine [13].
• Rhabdomyolysis, pancreatitis, and hyperglycemia with ziprasidone [14].

Chemical compound and disease context of Ziprasidone

• Estimated rankings of the atypical agents, based on the available literature, show that the relative risk of glucose intolerance/diabetes mellitus, hyperlipidaemia and hyperleptinaemia is highest for clozapine and olanzapine, moderately high for quetiapine, rather low for risperidone and lowest for ziprasidone [15].
• Successful switch to aripiprazole after induction of hyperprolactinemia by ziprasidone: a case report [16].
• RESULTS: The mean reductions in Brief Psychiatric Rating Scale (BPRS) total, BPRS agitation items, and Clinical Global Impressions-Severity scale scores were statistically significantly greater (p < .05, p < .01, and p < .01, respectively) after ziprasidone i.m. treatment compared with haloperidol i.m. treatment [17].
• In addition to its low liability for movement disorders and its favorable tolerability record in short- and long-term clinical trials, ziprasidone is associated with a favorable metabolic safety profile (in terms of its effect on plasma lipid and glucose levels) and a negligible effect on weight [18].
• RESULTS: Ziprasidone treatment was associated with a significant weight loss of 8.1 lb (3.6 kg) as well as a significant reduction in total cholesterol and triglycerides (p < or =.05) [19].

Biological context of Ziprasidone

• Pharmacokinetics and therapeutics of acute intramuscular ziprasidone [20].
• The psychopharmacology of ziprasidone: receptor-binding properties and real-world psychiatric practice [21].
• There is no evidence of genetic polymorphism in aldehyde oxidase, and thus it not surprising that ziprasidone exposure demonstrates unimodality in humans [22].
• The effects on weight and food intake of olanzapine (1 mg/kg), haloperidol (1 mg/kg), and ziprasidone (10 mg/kg) were also compared in a 3-week treatment experiment [23].
• Episodes of arrhythmic activity were commonly observed, and beat-to-beat variability of action potential duration was increased, during exposure of hearts to cisapride, ziprasidone, quinidine, and moxifloxacin but not during exposure of hearts to ranolazine or pentobarbital, in the presence of ATX-II [24].

Anatomical context of Ziprasidone

• CONCLUSIONS: The preferential increase in DA release in rat prefrontal cortex produced by ziprasidone is mediated by 5-HT(1A) receptor activation [25].
• A comparison of the effects of loxapine with ziprasidone and thioridazine on the release of dopamine and acetylcholine in the prefrontal cortex and nucleus accumbens [26].
• In Xenopus oocytes, ziprasidone exhibited less potent block of wild-type hERG current (IC(50)=2.8microM, 0mV, 23 degrees C) [27].
• The effects of ziprasidone on regional c-Fos expression in the rat forebrain [28].
• Ziprasidone-induced c-Fos expression was dose-dependent with significant (p<0.05) c-Fos expression observed in the nucleus accumbens (shell and core) and caudate putamen (lateral and medial) at 3 and 10 mg/kg and in the lateral septum at 10 mg/kg [28].

Associations of Ziprasidone with other chemical compounds

• This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic [10].
• Overall, these new techniques have resulted in a number of novel antipsychotics such as risperidone, sertindole, olanzapine, seroquel, zotepine and ziprasidone, whose design, synthesis and testing has benefited enormously from the accumulated knowledge base of the past 50 years [29].
• Despite the small sample size and short duration of the trial, the improvement in CGI-S with both ziprasidone 160 mg/day and haloperidol 15 mg/day was statistically significantly greater than with ziprasidone 4 mg/day (p = 0.001 andp = 0.005, respectively) [30].
• We compared a single oral dose of 20 mg ziprasidone (N = 30) with that of 10 mg diazepam (N = 30) and placebo (N = 30) in a randomized, parallel-group, double-blind study [31].
• Phase 1 is a double-blinded randomized clinical trial comparing treatment with the second generation antipsychotics olanzapine, quetiapine, risperidone, and ziprasidone to perphenazine, a midpotency first generation antipsychotic [32].
• These findings demonstrate that switching from risperidone or olanzapine to ziprasidone is associated with sustained, clinically significant improvements in weight and plasma lipids [33].

Gene context of Ziprasidone

• Ziprasidone also exhibits potent interaction with 5-HT2C, 5-HT1D, and 5-HT1A receptors in human brain tissue, characteristics that predict heightened negative symptom relief, enhanced modulation of mood, cognitive improvement, and reduced motor dysfunction [21].
• Quetiapine and ziprasidone are metabolized by CYP3A4 [34].
• Similar in vitro inhibition of CYP2D6 (Ki 6.9-16 microM) and CYP3A4 (Ki 64-80 microM) was obtained with ziprasidone, risperidone and 9-hydroxyrisperidone [35].
• Ziprasidone possesses an in vitro 5-HT2A/dopamine D2 receptor affinity ratio higher than any clinically available antipsychotic agent [36].
• The atypical antipsychotics clozapine, olanzapine, and ziprasidone (but not haloperidol) enhanced DA release in the mPFC of wild-type but not 5-HT1A knock-out mice after systemic and local (clozapine and olanzapine) administration in the mPFC [37].

Analytical, diagnostic and therapeutic context of Ziprasidone

• Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia [7].
• The affinity of ziprasidone for these receptors in vivo in patients was examined in a positron emission tomography (PET) study [38].
• This review of pharmacokinetic and clinical trials of ziprasidone versus placebo and active comparators focuses on the safety and tolerability of both the intramuscular and oral formulations [18].
• METHOD: Medical records were reviewed retrospectively to identify consecutive patients who were admitted to our neuropsychiatry service with the presenting complaint of dementia (DSM-IV) with agitation and who were given intramuscular ziprasidone and then administered an electrocardiogram (ECG) (N = 23) [39].
• The rapid clearance of ziprasidone from plasma after an intramuscular administration results in little to no persistence of plasma drug level when switching from intramuscular to oral drug administration [20].

References