title: From clinical research to clinical practice: a 4-year review of ziprasidone.
abstract: 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 D2 receptors, inverse agonist activity at serotonin (5-HT)2A receptors, agonist activity at 5-HTlA receptors, and a relatively high affinity for the serotonin and norepinephrine transporters. The 5-HTIA affinity, together with the inhibitory effect on mono-amine 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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 101 Woodruff Circle, Atlanta, GA 30322, USA. cnemero@emory.edu
authors.forename: Charles B
authors.initials: CB
authors.lastname: Nemeroff
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Weiden
authors.forename: Philip D
authors.initials: PD
authors.lastname: Harvey
authors.forename: John W
authors.initials: JW
authors.lastname: Newcomer
authors.forename: Alan F
authors.initials: AF
authors.lastname: Schatzberg
authors.forename: Clinton D
authors.initials: CD
authors.lastname: Kilts
authors.forename: David G
authors.initials: DG
authors.lastname: Daniel
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018849:Controlled Clinical Trials as Topic; D018492:Dopamine Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D019964:Mood Disorders / Q000188:drug therapy; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011618:Psychotic Disorders / Q000188:drug therapy*; D012559:Schizophrenia / Q000188:drug therapy*; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D010879:Piperazines; D012702:Serotonin Antagonists; D013844:Thiazoles; C092292:ziprasidone