Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia

• Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study (1,2,3)
  • double-blind, US study included a broad population of patients (n=1493) with chronic schizophrenia
    • minimal exclusion criteria and allowed co-existing conditions and use of other medications
    • publically funded
      • Phase 1
        • patients were randomly allocated to treatment with olanzapine, quetiapine, risperidone, ziprasidone (not available in the UK) or the typical antipsychotic, perphenazine for up to 18 months
          • doses were adjusted within a defined range according to clinical judgment
          • those receiving an atypical antipsychotic who discontinued treatment could be randomised to an alternative atypical antipsychotic in phase 2
            • Phase 2 had two arms:
              • A: ziprasidone vs. olanzapine, quetiapine, or risperidone; 2 or,
              • B: clozapine (open-label) vs. olanzapine, quetiapine, or risperidone
              • primary outcome in all phases was time to discontinuation for any reason - this endpoint reflects both clinician and patient judgements about efficacy and tolerability
      • Main Results
        • only 26% of patients (range 18–36%) completed the study on their first assigned antipsychotic in phase 1:
          • 10–19% of patients discontinued treatment because of intolerable side effects
          • 15–28% for lack of efficacy
          • 24–34% discontinued first assigned antipsychotic for other reasons
          • time to discontinuation for any reason:
            • was significantly longer for olanzapine than for risperidone or quetiapine, but not for perphenazine or ziprasidone
          • in comparison with other treatments
            • olanzapine was associated with the lowest rate of discontinuations for efficacy reasons (15% vs. 24–28%)
              • however olanzapine was associated with the highest rate of discontinuations due to side effects (19% vs. 10–16%), notably weight gain or metabolic effects (9% vs. 1–4%, P<0.001)
          • more patients discontinued perphenazine due to extrapyramidal effects (8% vs. 2–4 %, P=0.002), and more patients discontinued quetiapine for anticholinergic side effects (31% vs. 20–25%, P<0.001)
        • in phase 2, many patients who discontinued their assigned atypical were able to successfully complete the study on an alternative
          • in phase 2A
            • the times to discontinuation for patients switched to risperidone or olanzapine were significantly longer than for those switched to quetiapine or ziprasidone
          • clozapine appeared more effective than the other atypical antipsychotics in phase 2B - this result should be judged however in the context of the low number of patients in this phase questions the validity of this finding
      • Conclusions
        • evidence from this study suggests that there is little to choose in terms of overall effectiveness between the antipsychotics studied, including the typical antipsychotic, perphenazine
        • all antipsychotics studied were associated with high rates of intolerable side effects and failure to control symptoms
        • for these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic (3). However excluding clozapine (which requires careful safety monitoring), olanzapine appeared the most effective of the other atypical agents, although its benefits were limited by unacceptable weight gain and metabolic effects - however the olanzapine doses used were high (mean modal dose 20.1 mg) relative to the UK licensed dose range of 5–20mg daily, which may limit the relevance of these findings to UK clinical practice
        • "...The CATIE study clearly identifies the need for individualised antipsychotic treatment for patients with schizophrenia. Doctors and patients should carefully evaluate the tradeoffs between efficacy and side effects, to choose the antipsychotic (atypical or typical) that is most likely to be acceptable. No one antipsychotic is suitable for everyone (4)"

Reference:

1. Lieberman JA et al. New Engl J Med 2005;353:1209–23
2. Stroup TS et al. Am J Psychiatry 2006;163:611–22
3. McEvoy JP et al.Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 2006;163:600–10.
4. MeReC Extra 2006; 23:1-2.