NDLI: Ziprasidone for psychotic disorders: a meta-analysis and systematic review of the relationship between pharmacokinetics, pharmacodynamics, and clinical profile.

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Ziprasidone for psychotic disorders: a meta-analysis and systematic review of the relationship between pharmacokinetics, pharmacodynamics, and clinical profile.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Stip, Emmanuel Zhornitsky, Simon Moteshafi, Hoda Létourneau, Geneviève Stikarovska, Irena Potvin, Stéphane Tourjman, Valérie
Description	Country affiliation: Canada Author Affiliation: Stip E ( Department of Psychiatry, University of Montréal, Montréal, Québec, Canada. emmanuel.stip@umontreal.ca)
Abstract	BACKGROUND: Among atypical antipsychotics, ziprasidone exhibits a unique clinical profile. However, prescription rates for this medication remain among the lowest of all atypical antipsychotics. OBJECTIVE: The present meta-analysis examined premature study discontinuation (PSD) and dose-response associated with ziprasidone. Furthermore, a systematic review of the clinical pharmacokinetic and pharmacodynamic properties and tolerability of ziprasidone was conducted to explain the meta-analytic findings. METHODS: A systematic search was performed in the electronic databases PubMed and EMBASE using the key words ziprasidone, randomized, positron emission tomography, pharmacokinetic, and tolerability. This search looked for open-label or blinded studies of oral ziprasidone use in patients with psychoses (schizophrenia-spectrum disorders and/or bipolar mania) published between January 1, 1992, and February 1, 2011. Comparisons with antipsychotics for which there were <3 studies in total were excluded. PSD (all causes) was used as a measure of overall effectiveness. RESULTS: Thirty-one studies were included in the final analysis. The rates of PSD were significantly higher with ziprasidone compared with olanzapine (inefficacy and all causes, P < 0.001) and risperidone (all causes, P = 0.004). In contrast, the rates of PSD due to inefficacy and adverse events were significantly lower with ziprasidone compared with quetiapine (P = 0.03) and haloperidol (P = 0.03), respectively. On dose-response analysis, the rate of all-cause PSD was significantly lower with combined 120-160 mg/d compared with placebo (P = 0.001). Low levels of hyperprolactinemia and weight gain/metabolic adverse events, and moderate extrapyramidal symptoms and corrected QT-interval prolongation were reported with ziprasidone use. Ziprasidone exposure was increased when the medication was administered with food, irrespective of fat content. Ziprasidone 120-160 mg/d was correlated with 60% to 80% occupancy in studies of D(2) binding with the administration of multiple doses. However, the same occupancy was achieved with single-dose administration at much lower doses (20-60 mg/d). CONCLUSIONS: The findings from this meta-analysis and review suggest that ziprasidone 120-160 mg/d is a less effective treatment for psychotic disorders compared with olanzapine and risperidone, but that the low levels of hyperprolactinemia and weight gain/metabolic adverse events associated with ziprasidone may make it a useful option in patients in whom antipsychotics are poorly tolerated for these reasons.
File Format	HTM / HTML
ISSN	01492918
Issue Number	12
Volume Number	33
e-ISSN	1879114X
Journal	Clinical Therapeutics
Language	English
Publisher	Elsevier
Publisher Date	2011-12-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Pharmacology Antipsychotic Agents Administration & Dosage Pharmacokinetics Dopamine Antagonists Piperazines Psychotic Disorders Drug Therapy Thiazoles Adverse Effects Dopamine D2 Receptor Antagonists Dose-response Relationship, Drug Evidence-based Medicine Food-drug Interactions Humans Patient Selection Diagnosis Metabolism Psychology Receptors, Dopamine D2 Risk Assessment Treatment Outcome Journal Article Meta-analysis Research Support, Non-u.s. Gov't Review
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmacology (medical)

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