For more than 60 years, antipsychotics have been the cornerstone of schizophrenia treatment. In the 1990s, second-generation, also known as atypical, antipsychotics were introduced, offering the prospect of superior efficacy and a better safety profile. Despite this, there was a lack of consistent and robust clinical studies on long-term improvement with atypical, compared with conventional antipsychotics. CATIE was a randomized, double-blind study designed to compare the effectiveness of atypical and conventional antipsychotic drugs.
A total of 1493 patients with schizophrenia aged 18 to 65 were randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), risperidone (1.5 to 6.0 mg per day), or ziprasidone (40 to 160 mg per day) for up to 18 months or until treatment was discontinued. The primary outcome measure was the discontinuation of treatment for any cause. A number of secondary endpoints were included to further assess efficacy and safety of treatment.
Overall, 74% of patients in the study discontinued their antipsychotic before 18 months (64% olanzapine, 75% perphenazine, 82% quetiapine, 74% risperidone, 79% ziprasidone). The time to discontinuation of treatment was significantly longer in the olanzapine group versus quetiapine (HR=0.63; p<0.001) and risperidone (HR=0.75; p=0.002). Numerical improvements were seen with olanzapine, versus perphenazine (HR=0.78; p=0.021) and ziprasidone (HR=0.76; p=0.028). However, the results did not reach predefined statistical significance. Fewer patients in the olanzapine group than in the other 4 groups were hospitalized for an exacerbation of schizophrenia (11% versus 15-20%, p<0.001). Olanzapine was associated with more discontinuation for weight gain or metabolic effects, while perphenazine was associated with more discontinuation for extrapyramidal effects.
Patients receiving olanzapine experienced a longer time to discontinuation, compared with other antipsychotics, but they also had greater weight gain, hyperglycemia, and hyperlipidemia.