Effects of antipsychotic medications on psychosocial functioning in patients with chronic schizophrenia: findings from the NIMH CATIE study.

OBJECTIVE: This study examined the relative effects of the second-generation antipsychotic drugs and an older representative agent on psychosocial functioning in patients with chronic schizophrenia. METHOD: Consenting patients were enrolled in the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project. In phase 1, patients were randomly assigned to receive olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone for up to 18 months. Clozapine was included for patients who chose this pathway after discontinuing phase 1 due to inefficacy; all other patients received another second-generation antipsychotic. Psychosocial functioning was assessed using the Quality of Life Scale. RESULTS: Psychosocial functioning modestly improved for the one-third of phase 1 patients who reached the primary Quality of Life Scale analysis endpoint of 12 months (average effect size 0.19 SD units). Although for several of the drugs individually there were significant changes from baseline, overall there were no significant differences between the different agents. Results were similar at 6 and 18 months. There were no significant differences among the treatment groups in the amount of change in the Quality of Life Scale total score or subscale scores at 6, 12, or 18 months. Patients treated with clozapine in the efficacy pathway made comparable gains. Early treatment discontinuations, especially among patients most impaired at baseline, limited the ability to achieve more substantial functional gains. CONCLUSIONS: All antipsychotic treatment groups in all phases made modest improvements in psychosocial functioning. There were no differences among them after 6, 12, or 18 months. More substantial improvements would likely require more intensive adjunctive psychosocial rehabilitation interventions.

The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project: schizophrenia trial design and protocol development.

The National Institute of Mental Health initiated the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) program to evaluate the effectiveness of antipsychotic drugs in typical settings and populations so that the study results will be maximally useful in routine clinical situations. The CATIE schizophrenia trial blends features of efficacy studies and large, simple trials to create a pragmatic trial that will provide extensive information about antipsychotic drug effectiveness over at least 18 months. The protocol allows for subjects who receive a study drug that is not effective to receive subsequent treatments within the context of the study. Medication dosages are adjusted within a defined range according to clinical judgment. The primary outcome is all-cause treatment discontinuation because it represents an important clinical endpoint that reflects both clinician and patient judgments about efficacy and tolerability. Secondary outcomes include symptoms, side effects, neurocognitive functioning, and cost-effectiveness. Approximately 50 clinical sites across the United States are seeking to enroll a total of 1,500 persons with schizophrenia. Phase 1 is a double-blinded randomized clinical trial comparing treatment with the second generation antipsychotics olanzapine, quetiapine, risperidone, and ziprasidone to perphenazine, a midpotency first generation antipsychotic. If the initially assigned medication is not effective, subjects may choose one of the following phase 2 trials: (1) randomization to open-label clozapine or a double-blinded second generation drug that was available but not assigned in phase 1; or (2) double-blinded randomization to ziprasidone or another second generation drug that was available but not assigned in phase 1. If the phase 2 study drug is discontinued, subjects may enter phase 3, in which clinicians help subjects select an open-label treatment based on individuals' experiences in phases 1 and 2.