Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia
New England Journal of MedicinePublished 20 September 2005Open access
Jeffrey A. Lieberman, T. Scott Stroup, Joseph P. McEvoy, Marvin S. Swartz, Robert A. Rosenheck, Diana O. Perkins
Citations5,856
SJR quartileQ1
SJR score19.08
SNIP13.47
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone.
Abstract
The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism.
Keywords
MedicineNeuroscience
Journal of the Royal Statistical Society Series B (Statistical Methodology)Regression Models and Life-Tables
39,259 Citations1972D. R. Cox
BiometrikaA sharper Bonferroni procedure for multiple tests of significance
4,677 Citations1988Yosef Hochberg
Archives of General PsychiatryClozapine for the Treatment-Resistant Schizophrenic
4,090 Citations1988John M. Kane
In this relatively brief study, the apparently increased comparative risk of agranulocytosis requires that the use of clozapine be limited to selected treatment-resistant patients.
American Journal of PsychiatryAntipsychotic-Induced Weight Gain: A Comprehensive Research Synthesis
2,380 Citations1999David B. Allison, Janet L. Mentore +5 more
Among the newer antipsychotic agents, clozapine appears to have the greatest potential to induce weight gain, and ziprasidone the least, and the differences among newer agents may affect compliance with medication and health risk.
JAMAPractical Clinical Trials
1,693 Citations2003Sean Tunis, Daniel Stryer +1 more
Increasing the supply of pragmatic or practical clinical trials will depend on the development of a mechanism to establish priorities for these studies, significant expansion of an infrastructure to conduct clinical research within the health care delivery system, more reliance on high-quality evidence by health care decision makers, and a substantial increase in public and private funding forThese studies.
BMJAtypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis
1,065 Citations2000John Geddes, Nick Freemantle +2 more
There is no clear evidence that atypical antipsychotics are more effective or are better tolerated than conventional antipsychotic drugs.
Archives of General PsychiatryA Meta-analysis of the Efficacy of Second-Generation Antipsychotics
1,043 Citations2003John M. Davis, Nancy Chen +1 more
Molecular PsychiatryTreatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs
968 Citations2004Seiya Miyamoto, G E Duncan +2 more
A brief review and critique of the current therapeutic armamentarium for treating schizophrenia and drug development strategies and theories of mechanisms of action of antipsychotic drugs is provided, and focuses on novel targets for therapeutic agents for future drug development.
Schizophrenia ResearchEfficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials
801 Citations1999Stefan Leucht, Gabriele Pitschel‐Walz +2 more
All of the 4 new drugs are more effective than placebo, but the magnitude of the effect is only moderate, and all new antipsychotics are associated with less frequent use of antiparkinson medication than haloperidol.
The LancetNew generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis
727 Citations2003Stefan Leucht, Kristian Wahlbeck +2 more
New generation drugs were moderately more efficacious than low-potency antipsychotics, largely irrespective of the comparator doses used, and potential advantages in efficacy of the new generation drugs should be a factor in clinical treatment decisions to use these rather than conventional drugs.
Schizophrenia BulletinThe Effects of Atypical Antipsychotic Drugs on Neurocognitive Impairment in Schizophrenia: A Review and Meta-analysis
692 Citations1999Richard S.E. Keefe, S. G. Silva +2 more
The extent to which 15 studies on the effect of atypical antipsychotics met newly established standards for research design in studies of treatment effects on cognitive function in schizophrenia is determined and directions for the development of new therapeutic strategies are suggested.
Schizophrenia BulletinThe National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Project: Schizophrenia Trial Design and Protocol Development
648 Citations2003T. Scott Stroup, Joseph P. McEvoy +8 more
The CATIE schizophrenia trial blends features of efficacy studies and large, simple trials to create a pragmatic trial that will provide extensive information about antipsychotic drug effectiveness over at least 18 months.
American Journal of PsychiatryEffectiveness of Second-Generation Antipsychotics in Patients With Treatment-Resistant Schizophrenia: A Review and Meta-Analysis of Randomized Trials
636 Citations2001Miranda Chakos, J.A. Lieberman +3 more
It is confirmed that treatment-resistant schizophrenic patients have more favorable outcomes when treated with clozapine rather than a typical antipsychotic, as reflected by Brief Psychiatric Rating Scale total score, categorical response rate, Scale for the Assessment of Negative Symptoms score, Simpson-Angus Rating Scale score, and compliance rate.
New England Journal of MedicineA Comparison of Risperidone and Haloperidol for the Prevention of Relapse in Patients with Schizophrenia
611 Citations2002John G. Csernansky, Ramy Mahmoud +1 more
Adult outpatients with clinically stable schizophrenia or schizoaffective disorder have a lower risk of relapse if they are treated with risperidone than if they were treated with haloperidol.
American Journal of PsychiatryRelapse Prevention in Schizophrenia With New-Generation Antipsychotics: A Systematic Review and Exploratory Meta-Analysis of Randomized, Controlled Trials
518 Citations2003Stefan Leucht, Thomas R. E. Barnes +4 more
Overall, the currently available data suggest that new-generation antipsychotic drugs have the potential to reduce relapse rates.
Journal of Clinical PsychopharmacologyDose Response and Dose Equivalence of Antipsychotics
357 Citations2004John M. Davis, Nancy Chen
Evidence from randomized, placebo-controlled studies of patients with schizophrenia or schizoaffective disorder, which compared 2 or more doses of an antipsychotic to calculate the dose-response curve is reviewed to find 3.3 to 10 mg haloperidol to be the near-maximal ED range.
American Journal of PsychiatryEvidence of Clozapine’s Effectiveness in Schizophrenia: A Systematic Review and Meta-Analysis of Randomized Trials
352 Citations1999Kristian Wahlbeck, Maxim V. Cheine +2 more
This meta-analysis confirms that clozapine is more effective than conventional neuroleptics in reducing symptoms of patients with both treatment-resistant and nonresistant schizophrenia.
Archives of General PsychiatryGlucose Metabolism in Patients With Schizophrenia Treated With Atypical Antipsychotic Agents
319 Citations2005David C. Henderson, Enrico Cagliero +10 more
Both nonobese clozapine- and olanzapine's and risperidone's treatment with atypical antipsychotic agents displayed significant insulin resistance and impairment of glucose effectiveness compared with ris peridone-treated subjects.
JAMAEffectiveness and Cost of Olanzapine and Haloperidol in the Treatment of Schizophrenia<SUBTITLE>A Randomized Controlled Trial</SUBTITLE>
315 Citations2003Robert A. Rosenheck
Olanzapine does not demonstrate advantages compared with haloperidol (in combination with prophylactic benztropine) in compliance, symptoms, extrapyramidal symptoms, or overall quality of life, and its benefits in reducing akathisia and improving cognition must be balanced with the problems of weight gain and higher cost.
American Journal of PsychiatryNegative symptoms: a path analytic approach to a double-blind, placebo- and haloperidol-controlled clinical trial with olanzapine
303 Citations1997Gary D. Tollefson, T.M. Sanger
The results suggest that the negative symptoms of schizophrenia are directly responsive to treatment, and contribute to the hypothesis that negative symptoms may be under the influence of several neurotransmitters within one or more neuroanatomic circuits.
Archives of General PsychiatryDepressive Signs and Symptoms in Schizophrenia
262 Citations1998Gary D. Tollefson, T.M. Sanger +2 more
Archives of General PsychiatryAn Assessment of the Independent Effects of Olanzapine and Risperidone Exposure on the Risk of Hyperlipidemia in Schizophrenic Patients
234 Citations2002Carol E. Koro, Donald O. Fedder +6 more
A strong association between olanZapine exposure and hyperlipidemia in schizophrenic patients is observed and the possible metabolic consequences of olanzapine use should be given serious consideration by treating physicians.
PsychopharmacologyDropout rates in randomised antipsychotic drug trials
169 Citations2001Kristian Wahlbeck, Arja Tuunainen +2 more
Trial data implicate that a better compliance can be achieved by favouring atypical drugs rather than conventional alternatives in the treatment of schizophrenia, however, this effect is found only when groups treated with the atypicals antipsychotic clozapine are included in the analysis.
Schizophrenia BulletinNeurocognitive Assessment in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Project Schizophrenia Trial: Development, Methodology, and Rationale
114 Citations2003Richard S.E. Keefe, Richard C. Mohs +6 more
The neurocognitive methods used in the schizophrenia trial of the CATIE project are described, including the selection and training of neuroc cognitive raters, patient inclusion criteria for assessment, rationale for the choice of Neurocognitive instruments, and methodology for each neuroc Cognitive test.
Schizophrenia BulletinAssessing Clinical and Functional Outcomes in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial
109 Citations2003M S Swartz, Diana O. Perkins +4 more
The rationale for the measurement approach adopted for the CATIE schizophrenia trial is described, a brief overview of the selected measures is provided, and the process of training assessment raters for a large and geographically dispersed study group is described.
Schizophrenia ResearchNewer atypical antipsychotic medication in comparison to clozapine: a systematic review of randomized trials
102 Citations2002Arja Tuunainen, Kristian Wahlbeck +1 more
The equal effectiveness and tolerability of new atypical drugs in comparison with clozapine is not yet demonstrated, and more trials of sufficient power, with longer duration, and measuring clinically important outcomes are urgently needed.
Harvard Review of PsychiatryOptimal Dosing of Atypical Antipsychotics in Adults: A Review of the Current Evidence
90 Citations2002Leslie Citrome, Jan Volavka
The percentage of patients receiving quetiapine at doses above the manufacturer's recommended maximum is higher than would be expected, further illustrating that dosing ranges established during registration studies may not reflect the needs of day-to-day practice.
Schizophrenia BulletinStatistical Approaches to Effectiveness Measurement and Outcome-Driven Re-Randomizations in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Studies
44 Citations2003Sonia M. Davis, Gary G. Koch +2 more
This work discusses the CATIE strategy for addressing many hypotheses within the context of one clinical trial while controlling the overall type I error rate, and provides motivation for the use of two effectiveness outcomes: time to all-cause discontinuation and composite endpoints that combine outcomes from multiple domains.
Schizophrenia BulletinChanging Environments and Alternative Perspectives in Evaluating the Cost-Effectiveness of New Antipsychotic Drugs
19 Citations2003Robert A. Rosenheck, Jennifer Doyle +2 more
In conclusion, cost-effectiveness, as evaluated in studies like CATIE, will increasingly need to be tied to service system contingencies, environments, and evaluation perspectives.
Schizophrenia BulletinApproaches to Multisite Clinical Trials: The National Institute of Mental Health Perspective
14 Citations2003Barry D. Lebowitz, Benedetto Vitiello +1 more
The need for large multisite trials; the mechanisms for addressing this need; and the various approaches that have been used are described.