PMID- 20399985
OWN - NLM
STAT- MEDLINE
DCOM- 20100730
LR  - 20131121
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 32
IP  - 3
DP  - 2010 Mar
TI  - Effects of high-dose ziprasidone and haloperidol on the QTc interval after 
      intramuscular administration: a randomized, single-blind, parallel-group study in 
      patients with schizophrenia or schizoaffective disorder.
PG  - 472-91
LID - 10.1016/j.clinthera.2010.03.003 [doi]
AB  - BACKGROUND: Antipsychotic agents have been associated with a prolonged QT 
      interval. Data on the effects of ziprasidone and haloperidol on the QTc interval 
      are lacking. OBJECTIVE: This study aimed to characterize the effects of 2 
      high-dose intramuscular injections of ziprasidone and haloperidol on the QTc 
      interval at T(max). METHODS: This randomized, single-blind study enrolled 
      patients with schizophrenia or schizoaffective disorder in whom long-term 
      antipsychotic therapy was indicated. Patients were randomized to receive 2 
      high-dose intramuscular injections of ziprasidone (20 and 30 mg) or haloperidol 
      (7.5 and 10 mg) separated by 4 hours. The primary outcome measure was the mean 
      change from baseline in QTc at the T(max) of each injection. Each dose 
      administration was followed by serial ECG and blood sampling for pharmacokinetic 
      determinations. Twelve-lead ECG data were obtained immediately before and at 
      predetermined times after injections. ECG tracings were read by a blinded central 
      reader. Blood samples were obtained immediately before and after injections. 
      Point estimates and 95% CIs for mean QTc and changes from baseline in QTc were 
      estimated. No between-group hypothesis tests were conducted. For the assessments 
      of tolerability and safety profile, patients underwent physical examination, 
      including measurement of vital signs, clinical laboratory evaluation, and 
      monitoring for adverse events (AEs) using spontaneous reporting. RESULTS: A total 
      of 59 patients were assigned to treatment, and 58 received study medication 
      (ziprasidone, 31 patients; haloperidol, 27; age range, 21-72 years; 79% male). 
      After the first injection, mean (95% CI) changes from baseline were 4.6 msec 
      (0.4-8.9) with ziprasidone (n = 25) and 6.0 msec (1.4-10.5) with haloperidol (n = 
      24). After the second injection, these values were 12.8 msec (6.7-18.8) and 14.7 
      msec (10.2-19.2), respectively. Mild and transient changes in heart rate and 
      blood pressure were observed with both treatments. None of the patients had a QTc 
      interval >480 msec. Two patients in the ziprasidone group experienced QTc 
      prolongation >450 msec (457 and 454 msec) and QTc changes that exceeded 60 msec 
      (62 and 76 msec) relative to the time-matched baseline values. With haloperidol, 
      QTc interval values were <450 msec with no changes >60 msec. Treatment-emergent 
      AEs were reported in 29 of 31 patients (93.5%) in the ziprasidone group and 25 of 
      27 patients (92.6%) in the haloperidol group; most events were of mild or 
      moderate severity. Frequently reported AEs were somnolence (90.3% and 81.5%, 
      respectively), dizziness (22.6% and 7.4%), anxiety (16.1% and 7.4%), 
      extrapyramidal symptoms (6.5% and 33.3%), agitation (6.5% and 18.5%), and 
      insomnia (0% and 14.8%). CONCLUSIONS: In this study of the effects of high-dose 
      ziprasidone and haloperidol in patients with schizophrenic disorder, none of the 
      patients had a QTc interval >480 msec, and changes from baseline QTc interval 
      were clinically modest with both drugs. Both drugs were generally well tolerated.
CI  - Copyright 2010 Excerpta Medica Inc. All rights reserved.
FAU - Miceli, Jeffrey J
AU  - Miceli JJ
AD  - Pfizer Global Research and Development, New London, Connecticut 06320, USA. 
      jeffrey.j.miceli@pfizer.com
FAU - Tensfeldt, Thomas G
AU  - Tensfeldt TG
FAU - Shiovitz, Thomas
AU  - Shiovitz T
FAU - Anziano, Richard J
AU  - Anziano RJ
FAU - O'Gorman, Cedric
AU  - O'Gorman C
FAU - Harrigan, Rachel H
AU  - Harrigan RH
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Piperazines)
RN  - 0 (Thiazoles)
RN  - 6UKA5VEJ6X (ziprasidone)
RN  - J6292F8L3D (Haloperidol)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antipsychotic Agents/administration & dosage/*adverse effects/therapeutic use
MH  - Blood Pressure/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Electrocardiography
MH  - Female
MH  - Haloperidol/administration & dosage/*adverse effects/therapeutic use
MH  - Heart Rate/drug effects
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Piperazines/administration & dosage/*adverse effects/therapeutic use
MH  - Psychotic Disorders/drug therapy
MH  - Schizophrenia/drug therapy
MH  - Single-Blind Method
MH  - Thiazoles/administration & dosage/*adverse effects/therapeutic use
MH  - Young Adult
EDAT- 2010/04/20 06:00
MHDA- 2010/07/31 06:00
CRDT- 2010/04/20 06:00
PHST- 2009/11/04 00:00 [accepted]
PHST- 2010/04/20 06:00 [entrez]
PHST- 2010/04/20 06:00 [pubmed]
PHST- 2010/07/31 06:00 [medline]
AID - S0149-2918(10)00094-9 [pii]
AID - 10.1016/j.clinthera.2010.03.003 [doi]
PST - ppublish
SO  - Clin Ther. 2010 Mar;32(3):472-91. doi: 10.1016/j.clinthera.2010.03.003.