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

Am J Psychiatry. 2008 Jul;165(7):844-54. doi: 10.1176/appi.ajp.2008.07111779. Epub 2008 Jun 2.


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 There was worsening with olanzapine on the BPRS withdrawn depression factor.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: NCT00015548.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Activities of Daily Living
  • Aged
  • Aggression / psychology*
  • Alzheimer Disease / complications*
  • Alzheimer Disease / psychology*
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines / administration & dosage
  • Benzodiazepines / therapeutic use*
  • Brief Psychiatric Rating Scale
  • Cognition Disorders / diagnosis
  • Cognition Disorders / etiology
  • Dibenzothiazepines / administration & dosage
  • Dibenzothiazepines / therapeutic use*
  • Female
  • Humans
  • Male
  • Neuropsychological Tests
  • Olanzapine
  • Psychomotor Agitation / diagnosis
  • Psychomotor Agitation / drug therapy*
  • Psychomotor Agitation / etiology*
  • Psychotic Disorders / diagnosis
  • Psychotic Disorders / drug therapy*
  • Psychotic Disorders / etiology*
  • Quality of Life / psychology
  • Quetiapine Fumarate
  • Risperidone / administration & dosage
  • Risperidone / therapeutic use*
  • Surveys and Questionnaires


  • Antipsychotic Agents
  • Dibenzothiazepines
  • Benzodiazepines
  • Quetiapine Fumarate
  • Risperidone
  • Olanzapine

Associated data