Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia.


The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study compared the effectiveness of antipsychotic drugs on adults with schizophrenia in the U.S. Rates of discontinuation were high for all drugs. Olanzapine was the most effective drug, but was also most associated with weight gain and metabolic syndrome.


  • N=1,493 adults with schizophrenia, ages 18-65, were recruited at 57 sites in the U.S. and randomly assigned to receive one of five antipsychotics: olanzapine, perphenazine, quetiapine, risperidone, and ziprasidone.
  • Patients were followed for up to 18 months or until treatment was discontinued.
  • Primary outcome: discontinuation of treatment for any cause.
  • Secondary outcomes: inefficacy, intolerability due to weight gain, extrapyramidal side effects, sedation, scores on Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions (CGI) Scale.


  • Rates of discontinuation were high for all drugs (64%-82%)
  • Time to discontinuation of olanzapine for any cause was significantly longer than for quetiapine or risperidone. When compared to perphenazine or ziprasidone, the difference was not significant after adjustment for multiple comparisons.
  • Time to discontinuation due to lack of efficacy was significantly longer in olanzapine when compared to perphenazine, quetiapine, or risperidone. The difference was not significant for olanzapine compared to ziprasidone after adjusting for multiple comparisons.
  • Time to discontinuation due to side effects showed no significant difference among treatments.
  • Patients taking olanzapine gained the most weight (average 2 pounds per month). 30% of patients taking olanzapine gained 7% or more of their baseline body weight, compared with 7-16% (P<0.001) for the other groups.
  • Olanzapine was associated with the greatest increase in metabolic variables (glycosylated hemoglobin, total cholesterol, triglycerides). Only ziprasidone was associated with improvement in these variables.
  • Risperidone was the only drug associated with significantly increased prolactin.


Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med (2005) 353(12):1209–23

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