Document Detail


Atypical and conventional antipsychotic drugs in treatment-naive first-episode schizophrenia: a 52-week randomized trial of clozapine vs chlorpromazine.
MedLine Citation:
PMID:  12700715     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purported advantages of second-generation or "atypical" antipsychotics relative to first-generation antipsychotics have not been examined in patients with a first episode of schizophrenia. This flexible-dose study examined efficacy and safety in a randomized, double-blind, 52-week trial, comparing chlorpromazine (CPZ) and clozapine (CLZ) in treatment naive patients experiencing their first episode of schizophrenia. In all, 160 inpatients with first-episode schizophrenia or schizophreniform disorder were randomized to CPZ or CLZ and followed them for 52 weeks or until dropout. The primary efficacy measure was time to first remission and proportion of time remaining in remission. The analysis was supplemented by comparisons on a profile of clinical symptoms and side effects. Of these first-episode patients, 80% achieved remission within 1 year (79% CPZ, 81% CLZ). The Kaplan-Meier estimated median time to first remission was 8 weeks for CLZ vs 12 weeks for CPZ (chi(2)(1)=5.56, p=0.02). Both the rate of first achieving remission and the odds for being in remission during the trial were almost doubled for the CLZ group in comparison with the CPZ group. At 12 weeks, CLZ was superior on many rating scale measures of symptom severity while CPZ was not superior on any. These symptom differences remained significant when controlling for EPS differences. By 52 weeks many of the symptom differences between groups were no longer significantly different. Generally, CLZ produced fewer side effects than CPZ, particularly extrapyramidal side effects. There was no significant difference between treatments in weight change or glucose metabolism. For each prior year of untreated psychosis, there was a 15% decrease in the odds of achieving remission (OR=0.85; CI 0.75-0.95). A high proportion of first-episode patients remitted within 1 year. We detected no difference in the proportion of first-episode patients receiving CLZ or CPZ that achieved remission. However, first-episode patients receiving CLZ remitted significantly faster and remained in remission longer than subjects receiving CPZ. While the CLZ group showed significantly less symptomatology on some measures and fewer side effects at 12 weeks, the two treatment groups seemed to converge by 1 year. Longer duration of untreated psychosis was associated with lower odds of achieving remission.
Authors:
Jeffrey A Lieberman; Michael Phillips; Hongbin Gu; Scott Stroup; Peiyan Zhang; Lan Kong; Zhongfu Ji; Gary Koch; Robert M Hamer
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2003-03-26
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  28     ISSN:  0893-133X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-05-08     Completed Date:  2003-06-11     Revised Date:  2011-05-18    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  995-1003     Citation Subset:  IM    
Affiliation:
Department of Psychiatry, CB #7160, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160, USA. jlieberman@med.unc.edu
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Analysis of Variance
Antipsychotic Agents / adverse effects,  therapeutic use*
Chlorpromazine / adverse effects,  therapeutic use*
Clozapine / adverse effects,  therapeutic use*
Female
Follow-Up Studies
Humans
Male
Schizophrenia / drug therapy*
Grant Support
ID/Acronym/Agency:
MH 00537/MH/NIMH NIH HHS; MH 33127/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Antipsychotic Agents; 50-53-3/Chlorpromazine; 5786-21-0/Clozapine
Comments/Corrections
Comment In:
Schizophr Res. 2006 May;84(1):172-3   [PMID:  16563702 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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