High-dose oral ziprasidone versus conventional dosing in schizophrenia patients with residual symptoms: The ZEBRAS study

Donald C. Goff, Joseph Patrick McEvoy, Leslie Citrome, Arnold W. Mech, Juan R. Bustillo, Roberto Gil, Peter F Buckley, Theo C. Manschreck, Eric D. Achtyes, Eric A. Macklin

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)485-490
Number of pages6
JournalJournal of Clinical Psychopharmacology
Volume33
Issue number4
DOIs
StatePublished - Aug 1 2013

Fingerprint

Schizophrenia
Serum
Blood Pressure
ziprasidone
Psychotic Disorders
Therapeutics
Placebos

Keywords

  • high-dose ziprasidone
  • residual symptoms
  • schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

High-dose oral ziprasidone versus conventional dosing in schizophrenia patients with residual symptoms : The ZEBRAS study. / Goff, Donald C.; McEvoy, Joseph Patrick; Citrome, Leslie; Mech, Arnold W.; Bustillo, Juan R.; Gil, Roberto; Buckley, Peter F; Manschreck, Theo C.; Achtyes, Eric D.; Macklin, Eric A.

In: Journal of Clinical Psychopharmacology, Vol. 33, No. 4, 01.08.2013, p. 485-490.

Research output: Contribution to journalArticle

Goff, DC, McEvoy, JP, Citrome, L, Mech, AW, Bustillo, JR, Gil, R, Buckley, PF, Manschreck, TC, Achtyes, ED & Macklin, EA 2013, 'High-dose oral ziprasidone versus conventional dosing in schizophrenia patients with residual symptoms: The ZEBRAS study', Journal of Clinical Psychopharmacology, vol. 33, no. 4, pp. 485-490. https://doi.org/10.1097/JCP.0b013e3182977308
Goff, Donald C. ; McEvoy, Joseph Patrick ; Citrome, Leslie ; Mech, Arnold W. ; Bustillo, Juan R. ; Gil, Roberto ; Buckley, Peter F ; Manschreck, Theo C. ; Achtyes, Eric D. ; Macklin, Eric A. / High-dose oral ziprasidone versus conventional dosing in schizophrenia patients with residual symptoms : The ZEBRAS study. In: Journal of Clinical Psychopharmacology. 2013 ; Vol. 33, No. 4. pp. 485-490.
@article{8b9cbe0848b04d8893f5faa8001ab19f,
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.",
keywords = "high-dose ziprasidone, residual symptoms, schizophrenia",
author = "Goff, {Donald C.} and McEvoy, {Joseph Patrick} and Leslie Citrome and Mech, {Arnold W.} and Bustillo, {Juan R.} and Roberto Gil and Buckley, {Peter F} and Manschreck, {Theo C.} and Achtyes, {Eric D.} and Macklin, {Eric A.}",
year = "2013",
month = "8",
day = "1",
doi = "10.1097/JCP.0b013e3182977308",
language = "English (US)",
volume = "33",
pages = "485--490",
journal = "Journal of Clinical Psychopharmacology",
issn = "0271-0749",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - High-dose oral ziprasidone versus conventional dosing in schizophrenia patients with residual symptoms

T2 - The ZEBRAS study

AU - Goff, Donald C.

AU - McEvoy, Joseph Patrick

AU - Citrome, Leslie

AU - Mech, Arnold W.

AU - Bustillo, Juan R.

AU - Gil, Roberto

AU - Buckley, Peter F

AU - Manschreck, Theo C.

AU - Achtyes, Eric D.

AU - Macklin, Eric A.

PY - 2013/8/1

Y1 - 2013/8/1

N2 - 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.

AB - 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.

KW - high-dose ziprasidone

KW - residual symptoms

KW - schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=84879842516&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879842516&partnerID=8YFLogxK

U2 - 10.1097/JCP.0b013e3182977308

DO - 10.1097/JCP.0b013e3182977308

M3 - Article

C2 - 23775057

AN - SCOPUS:84879842516

VL - 33

SP - 485

EP - 490

JO - Journal of Clinical Psychopharmacology

JF - Journal of Clinical Psychopharmacology

SN - 0271-0749

IS - 4

ER -