Antipsychotics and schizophrenia: from efficacy and effectiveness to clinical decision-making.
OBJECTIVE
To comprehensively review the 2 recent and large antipsychotic effectiveness trials for treatment of schizophrenia: the United Kingdom's Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS), and the National Institute of Mental Health-initiated Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial.


METHODS
We present a review of the rationale, methodology, and findings to date from the CUtLASS and CATIE schizophrenia trials, including all primary and secondary outcomes.


RESULTS
The primary findings from both trials, CUtLASS and CATIE, suggest that first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) are equally effective in the treatment of schizophrenia. The exception is in treatment-resistant populations where clozapine exhibits superiority, compared with other SGAs. In the CATIE trial, there is a suggestion that olanzapine is superior in effectiveness, compared with other nonclozapine SGAs, although this seems to be mediated by past history of olanzapine use, and carries with it increased weight gain and metabolic adverse events. From a cost-effectiveness perspective, there is no evidence that SGAs are superior to FGAs, with findings suggesting the possibility that FGAs may be superior.


CONCLUSIONS
Past efficacy trials have strongly supported the position that SGAs are superior to FGAs in the treatment of schizophrenia and in side effect profile. Two large independent effectiveness trials, CUtLASS and CATIE, have offered a strong challenge to these claims. Both suggest that SGAs, except clozapine in the treatment-resistant population, offer little, if any, clinical benefits, and, moreover, harbour their own significant side effects.
Foussias
George
G
Schizophrenia Program, Centre for Addiction and Mental Health, Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario. george_foussias@camh.net
Remington
Gary
G
D014150:Antipsychotic Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D003024:Clozapine / Q000627:therapeutic use; D003362:Cost-Benefit Analysis; D003657:Decision Making; D006801:Humans; D009315:National Institute of Mental Health (U.S.); D000077152:Olanzapine; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome; D006113:United Kingdom; D014481:United States
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D003024:Clozapine; D000077152:Olanzapine