From clinical research to clinical practice: A 4-year review of ziprasidone

Charles B. Nemeroff, Jeffrey A. Lieberman, Peter J. Weiden, Philip D. Harvey, John W. Newcomer, Alan F. Schatzberg, Clinton D. Kilts, David G. Daniel

Research output: Contribution to journalReview articlepeer-review

63 Scopus citations


Ziprasidone is a second-generation antipsychotic that received Food and Drug Administration approval in February 2001. It has a unique receptor profile that includes high-affinity antagonist activity at dopamine D 2 receptors, inverse agonist activity at serotonin (5-HT) 2A receptors, agonist activity at 5-HT 1A receptors, and a relatively high affinity for the serotonin and norepinephrine transporters. The 5-HT 1A affinity, together with the inhibitory effect on monoamine reuptake, may underlie the hypothesized beneficial effects on comorbid affective and cognitive abnormalities in schizophrenia and schizoaffective disorder. The short-term efficacy of ziprasidone for core positive symptoms of schizophrenia appears to be comparable to other conventional and atypical antipsychotics. The short-term efficacy of ziprasidone in acute mania has been established based on two 3-week, double-blind, placebo-controlled trials. Open-label treatment for up to 52 weeks confirms the sustained efficacy and safety of ziprasidone in bipolar disorder. Maintenance studies in schizophrenia and schizoaffective disorder indicate that long-term ziprasidone therapy is effective in preventing relapse, while maintaining cognitive and psychosocial benefits. The safety database suggests that the overall cardiovascular and cerebrovascular risk associated with ziprasidone is lower than with other atypicals, with notably lower risk of drug-related increases in weight, glucose, or lipids. The data also suggest a modestly increased risk of QTc prolongation that is not dose related or linked to torsades de pointes. Switching to ziprasidone from other atypicals appears to improve both clinical symptoms and metabolic parameters, though more studies are needed to fully characterize these benefits. This monograph summarizes the efficacy, tolerability, and safety of oral ziprasidone in the treatment of schizophrenia, schizoaffective disorder, and bipolar mania.

Original languageEnglish (US)
Pages (from-to)1-19
Number of pages19
JournalCNS spectrums
Issue number11
StatePublished - Nov 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health


Dive into the research topics of 'From clinical research to clinical practice: A 4-year review of ziprasidone'. Together they form a unique fingerprint.

Cite this