TY - JOUR
T1 - Atypical and conventional antipsychotic drugs in treatmentnaive first-episode schizophrenia
T2 - A 52-week randomized trial of clozapine vs chlorpromazine
AU - Lieberman, Jeffrey A.
AU - Phillips, Michael
AU - Gu, Hongbin
AU - Stroup, Scott
AU - Zhang, Peiyan
AU - Kong, Lan
AU - Ji, Zhongfu
AU - Koch, Gary
AU - Hamer, Robert M.
N1 - Funding Information:
The study was conducted at the Beijing Hui Long Guan Hospital, one of the largest psychiatric hospitals in China, which is located 30 km from central Beijing and serves a catchment area population of 13 million people. Dr Phillips has worked in the PRC since 1985 and is the Director of the Research Center of Clinical Epidemiology at the Hui Long Guan Hospital. The study protocol was designed by the first and second authors (JL and MP). It conformed to international standards for research ethics and was approved by the Research Review Board of the Beijing Bureau of Health prior to its initiation and monitored annually while in progress. Funding for the study and medication supplies were provided by the Novartis Pharmaceutical Company. The authors had unrestricted access to the data; company personnel were not involved in the analysis of the data nor did they have any authority over publication.
Funding Information:
We acknowledge the assistance of the following staff members at Beijing Hui Long Guan Hospital in carrying out this project: (alphabetically listed) Peiran Guo, Feifei Li, Guowang Li (Deceased), Huaqing Li, Lanying Li, Xianyun Li, Mei Meng, Yajuan Niu, Lan Shang, Jiancheng Song, Deliang Yan, Fude Yang, Xiuqin Zhao, and Fengyan Zhu. The investigators appreciate the support and encouragement of Drs Peter Jager, Rajinder Judge, Jeffrey Schwimmer, and Rene Speigel of Novartis in the development and implementation of the study. This work was supported by USPHS grants MH00537, MH33127 (Dr Lieberman), the UNC Mental Health and Neuroscience Clinical Research Center, and the Novartis Pharmaceutical Company.
PY - 2003/5
Y1 - 2003/5
N2 - 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, doubleblind, 52-weektrial, 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 untildropout. 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 clinicalsymptoms 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 (χ2(l) — 5.56, p — 0.02). Both the rate of first achieving remission and the odds for being in remission during the trialwere 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 extrapyramidalside 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, firstepisode patients receiving CLZ remitted significantly faster and remained in remission longerthan 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.
AB - 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, doubleblind, 52-weektrial, 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 untildropout. 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 clinicalsymptoms 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 (χ2(l) — 5.56, p — 0.02). Both the rate of first achieving remission and the odds for being in remission during the trialwere 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 extrapyramidalside 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, firstepisode patients receiving CLZ remitted significantly faster and remained in remission longerthan 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.
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U2 - 10.1038/sj.npp.1300157
DO - 10.1038/sj.npp.1300157
M3 - Article
C2 - 12700715
AN - SCOPUS:0037712923
SN - 0893-133X
VL - 28
SP - 995
EP - 1003
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 5
ER -