Clinical symptom responses to atypical antipsychotic medications in Alzheimer's disease: phase 1 outcomes from the CATIE-AD effectiveness trial

Abstract

Objective: The study measured the effects of atypical antipsychotics on psychiatric and behavioral symptoms in patients with Alzheimer's disease and psychosis or agitated behavior.

Method: The Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) Alzheimer's disease effectiveness study included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior. Patients were assigned randomly to masked, flexible-dose treatment with olanzapine, quetiapine, risperidone, or placebo for up to 36 weeks. Patients could be randomly reassigned to a different medication at the clinician's discretion, which ended phase 1. Psychiatric and behavioral symptoms, functioning, cognition, care needs, and quality of life were measured at regular intervals.

Results: In relation to placebo, the last observation in phase 1 showed greater improvement with olanzapine or risperidone on the Neuropsychiatric Inventory total score, risperidone on the Clinical Global Impression of Changes, olanzapine and risperidone on the Brief Psychiatric Rating Scale (BPRS) hostile suspiciousness factor, and risperidone on the BPRS psychosis factor. There was worsening with olanzapine on the BPRS withdrawn depression factor. Among patients continuing phase 1 treatment at 12 weeks, there were no significant differences between antipsychotics and placebo on cognition, functioning, care needs, or quality of life, except for worsened functioning with olanzapine compared to placebo.

Conclusion: In this descriptive analysis of outpatients with Alzheimer's disease in usual care settings, some clinical symptoms improved with atypical antipsychotics. Antipsychotics may be more effective for particular symptoms, such as anger, aggression, and paranoid ideas. They do not appear to improve functioning, care needs, or quality of life.

Trial registration: ClinicalTrials.gov NCT00015548.

Figure 1

Change on clinical symptom measures between baseline and treatment week 12. ^ ^{^} Mean change scores for those patients continuing to take the assigned phase 1 medication at week 2, 4, 8, and 12 (observed cases at each timepoint) are shown. Change scores <0 reflect clinical improvement. Standard error bars are shown for week 12 results. Pairwise comparisons of least squares mean change score for each antipsychotic group vs. placebo group at each timepoint are shown here for descriptive purposes: *p<.05, **p<.01 (ANCOVA, adjusted for baseline score and pooled site, no adjustment for multiple comparisons). Significant pairwise comparisons between antipsychotic treatment groups are provided in the text. Discrepancies between the magnitude of between-group differences shown on the graphs and the results of antipsychotic-placebo pairwise comparisons are due to differences between observed means and least squares means, which adjust for baseline score and site variations.

Figure 1

Change on clinical symptom measures between baseline and treatment week 12. ^ ^{^} Mean change scores for those patients continuing to take the assigned phase 1 medication at week 2, 4, 8, and 12 (observed cases at each timepoint) are shown. Change scores <0 reflect clinical improvement. Standard error bars are shown for week 12 results. Pairwise comparisons of least squares mean change score for each antipsychotic group vs. placebo group at each timepoint are shown here for descriptive purposes: *p<.05, **p<.01 (ANCOVA, adjusted for baseline score and pooled site, no adjustment for multiple comparisons). Significant pairwise comparisons between antipsychotic treatment groups are provided in the text. Discrepancies between the magnitude of between-group differences shown on the graphs and the results of antipsychotic-placebo pairwise comparisons are due to differences between observed means and least squares means, which adjust for baseline score and site variations.

Figure 2

Distribution of CGI-C scores after 12 weeks of treatment in Phase 1.