Effectiveness of Atypical Antipsychotic Drugs in Patients with Alzheimer’s Disease


The Clinical Antipsychotic Trials of Intervention Effectiveness - Alzheimer’s Disease (CATIE-AD) phase 1 randomized patients with Alzheimer’s disease and psychosis, aggression, agitation to receive a second-generation antipsychotic (olanzapine, quetiapine, risperidone) or placebo. Olanzapine and risperidone were significantly less likely to be discontinued due to lack of efficacy, compared with placebo. However, these drugs had higher rates of discontinuation due to adverse events (sedation, extrapyramidal signs, confusion). The authors conclude that despite their efficacy, atypical antipsychotic drugs may have limited effectiveness in this population, due to adverse effects.


  • N=421 outpatients with Alzheimer’s disease and psychosis, aggression, or agitation were randomized (2:2:2:3) to receive:
    • Olanzapine (n=100)
    • Quetiapine (n=94)
    • Risperidone (n=85)
    • Placebo (n=142)
  • Randomization was under double-blind conditions, with identically appearing capsules that varied in size with lower or higher dose.
  • Doses adjusted as clinically indicated.
  • Patients followed for up to 36 weeks.
  • Setting: 42 sites (university clinics, VA medical centers, and private-practice sites) in the United States.
  • Main outcomes: time until discontinuation of treatment, and number of patients with at least minimal improvement on the Clinical Global Impression of Change (CGIC) scale at 12 weeks.


  • Median time to discontinuation of treatment due to lack of efficacy (P-values compared with placebo):
    • 26.7 weeks for risperidone (P=0.01)
    • 22.1 weeks for olanzapine (P<0.001)
    • 9.1 weeks for quetiapine (P=0.24)
    • 9.0 weeks for placebo
  • Percentage of patients who discontinued treatment due to intolerability (overall comparison: P<0.001):
    • 24% for olanzapine
    • 18% for risperidone
    • 16% for quetiapine
    • 5% for placebo
  • Sedation occurred in (overall comparison: P<0.001):
    • 24% with olanzapine
    • 22% with quetiapine
    • 15% with risperidone
    • 5% with placebo
  • Parkinsonism or extrapyramidal signs occurred in (overall comparison: P<0.001):
    • 12% with olanzapine
    • 12% with risperidone
    • 2% with quetiapine
    • 1% with placebo
  • Confusion or mental-status change occurred in (overall comparison: P=0.03):
    • 18% with olanzapine
    • 11% with risperidone
    • 6% with quetiapine
    • 5% with placebo
  • Improvement on CGIC scale did not differ significantly among treatments (overall comparison: P=0.22). Improvement observed in (P-value, compared with placebo):
    • 32% with olanzapine (P=0.05)
    • 29% with risperidone (P=0.37)
    • 26% with quetiapine (P=0.21)
    • 21% with placebo


Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med. 2006;355(15):1525-1538. doi:10.1056/NEJMoa061240.

View on PubMed