title: High-dose oral ziprasidone versus conventional dosing in schizophrenia patients with residual symptoms: the ZEBRAS study.
abstract: Uncontrolled studies have suggested that increasing the dose of ziprasidone above the standard maximum daily dose of 160 mg may be more effective for some patients with schizophrenia. To test this hypothesis, we conducted an 8-week, placebo-controlled, fixed-dose escalation trial comparing ziprasidone 160 versus 320 mg/d in individuals with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks. Of 75 randomized patients, 42 completed the study. Serum ziprasidone concentrations increased significantly in the high-dose group compared with the standard-dose group at week 4 but did not differ between groups at week 8. Both treatment groups exhibited significant symptomatic improvement. Response did not differ between treatment groups; however, in the high-dose group, higher ziprasidone serum concentrations were associated with better response at a trend level. Higher ziprasidone concentrations were also associated with reductions in diastolic blood pressure and, at a trend level, with more prominent negative symptoms and greater QTc prolongation. In summary, increasing the ziprasidone dose to 320 mg/d did not produce a sustained elevation in serum concentrations or symptomatic improvement compared with a standard ziprasidone dose of 160 mg/d.
authors.affiliation: Nathan Kline Institute, Orangeburg, NY 10962, USA. dgoff@nki.rfmh.org
authors.forename: Donald C
authors.initials: DC
authors.lastname: Goff
authors.forename: Joseph P
authors.initials: JP
authors.lastname: McEvoy
authors.forename: Leslie
authors.initials: L
authors.lastname: Citrome
authors.forename: Arnold W
authors.initials: AW
authors.lastname: Mech
authors.forename: Juan R
authors.initials: JR
authors.lastname: Bustillo
authors.forename: Roberto
authors.initials: R
authors.lastname: Gil
authors.forename: Peter
authors.initials: P
authors.lastname: Buckley
authors.forename: Theo C
authors.initials: TC
authors.lastname: Manschreck
authors.forename: Eric D
authors.initials: ED
authors.lastname: Achtyes
authors.forename: Eric A
authors.initials: EA
authors.lastname: Macklin
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone