CATIE
Effectiveness of antipsychotic drugs in patients with chronic schizophrenia
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Overview
Most antipsychotics had high discontinuation rates; olanzapine lasted longer but caused more metabolic effects.
Clinical takeaway
CATIE challenged the assumption that atypical antipsychotics were uniformly superior, emphasizing effectiveness, tolerability, and patient-specific tradeoffs.
Key result
74% discontinued study medication before 18 months (64% olanzapine, 75% perphenazine, 82% quetiapine, 74% risperidone, 79% ziprasidone); time to discontinuation was significantly longer with olanzapine than quetiapine or risperidone, but not perphenazine or ziprasidone.
Practice impact
Antipsychotic choice became more explicitly individualized around benefit, adverse effects, and adherence.
Evidence
Study design
Large pragmatic randomized double-blind effectiveness trial.
Enrollment
1,493
Follow-up
Up to 18 months.
Geography
United States
Clinical question
How do commonly used antipsychotics compare in real-world effectiveness for chronic schizophrenia?
Population
- Patients with chronic schizophrenia requiring antipsychotic treatment.
Intervention
Olanzapine, quetiapine, risperidone, ziprasidone, or perphenazine.
Comparator
Active antipsychotic comparators.
Primary outcome
Discontinuation of treatment for any cause.
74% discontinued before 18 months; olanzapine had the lowest discontinuation rate (64%) and significantly longer time to discontinuation than quetiapine or risperidone, but worst metabolic effects.
Median time to discontinuation
Key results
- Overall, 74% (1061 of 1432 who received at least one dose) discontinued the study medication before 18 months: 64% olanzapine, 75% perphenazine, 82% quetiapine, 74% risperidone, and 79% ziprasidone.
- Time to discontinuation for any cause was significantly longer with olanzapine than with quetiapine (p<0.001) or risperidone (p=0.002), but not significantly longer than with perphenazine (p=0.021) or ziprasidone (p=0.028) after adjustment for multiple comparisons.
- Olanzapine caused more weight gain and increases in glucose and lipid measures; perphenazine's efficacy appeared similar to quetiapine, risperidone, and ziprasidone.
Harms
- Olanzapine caused greater weight gain and metabolic abnormalities, with more discontinuation for weight gain or metabolic effects.
- Perphenazine was associated with more discontinuation for extrapyramidal effects.
Clinical Use
Practice impact
- Tempered blanket preference for second-generation antipsychotics and emphasized comparative effectiveness.
Applicability
- Chronic schizophrenia patients where adherence, tolerability, and metabolic risk dominate medication choice.
Limitations
- Discontinuation is pragmatic but influenced by clinician and patient preference.
- Excluded some patients with tardive dyskinesia from perphenazine assignment.
Common misinterpretations
- Do not summarize CATIE as 'first-generation equals second-generation' without discussing side-effect profiles and individual agents.
Related evidence
Citation
Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005;353(12):1209-1223. doi:10.1056/NEJMoa051688
The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons.
- PMID
- 16172203