PDF: CATIE-AD
(2006)Objective
To compare the effectiveness of olanzapine, quetiapine, and risperidone with placebo for treating psychosis, aggression, or agitation in outpatients with Alzheimer's disease
Study Summary
• Time to discontinuation for lack of efficacy favored olanzapine (22.1 wk) and risperidone (26.7 wk) vs quetiapine (9.1 wk) and placebo (9.0 wk) (P=0.002)
• CGIC improvement at 12 weeks: olanzapine 32%, quetiapine 26%, risperidone 29%, placebo 21% (P=0.22)
• Discontinuation due to intolerability: olanzapine 24%, quetiapine 16%, risperidone 18%, placebo 5% (P=0.009)
• Adverse effects offset efficacy advantages
Intervention
Olanzapine (mean 5.5 mg/day), quetiapine (mean 56.5 mg/day), risperidone (mean 1.0 mg/day), or placebo; doses clinician-adjusted; up to 36 weeks
Inclusion Criteria
Alzheimer's disease (DSM-IV or probable AD); MMSE 5-26; ambulatory; living at home or assisted living; psychosis, aggression, or agitation severe enough to warrant antipsychotic treatment; symptoms nearly daily for >=1 week or intermittent for >=4 weeks
Study Design
Arms: Array
Patients per Arm: Olanzapine: 100; Quetiapine: 94; Risperidone: 85; Placebo: 142
Outcome
• Discontinuation for lack of efficacy: olanzapine and risperidone superior to quetiapine and placebo, P=0.002
• CGIC improvement at 12 wk: 32% vs 26% vs 29% vs 21%, P=0.22
• Discontinuation for intolerability: higher with antipsychotics (24%, 16%, 18%) vs placebo (5%), P=0.009
• Weight gain, sedation, and metabolic effects offset efficacy
Bottom Line
Atypical antipsychotics were not significantly better than placebo for the primary outcome of time to discontinuation of treatment in AD patients with behavioral symptoms. While olanzapine and risperidone showed some efficacy advantage over quetiapine and placebo for specific symptom domains, adverse effects (sedation, weight gain, metabolic changes, extrapyramidal symptoms) offset these benefits. This landmark trial established that the risk-benefit ratio of antipsychotics in AD is unfavorable for most patients.
Major Points
- CATIE-AD was a 42-site, NIMH-funded, double-blind, placebo-controlled effectiveness trial enrolling 421 outpatients with AD and clinically significant psychosis, aggression, or agitation.
- Phase 1 randomized patients 2:2:2:3 to olanzapine, quetiapine, risperidone, or placebo. Doses were clinician-adjusted (olanzapine mean 5.5 mg/d, quetiapine mean 56.5 mg/d, risperidone mean 1.0 mg/d) for up to 36 weeks.
- The primary outcome (time to discontinuation of treatment for any reason) showed no significant differences: median 8.1 weeks (olanzapine), 5.3 weeks (quetiapine), 7.4 weeks (risperidone), 8.0 weeks (placebo); P=0.52.
- Time to discontinuation for lack of efficacy favored olanzapine (22.1 wk) and risperidone (26.7 wk) over quetiapine (9.1 wk) and placebo (9.0 wk) (P=0.002), suggesting some symptom control.
- CGIC improvement at 12 weeks was not significantly different: 32% olanzapine, 26% quetiapine, 29% risperidone, 21% placebo (P=0.22).
- Discontinuation rates due to intolerability were significantly higher with antipsychotics: olanzapine 24%, quetiapine 16%, risperidone 18%, vs placebo 5% (P=0.009).
- Weight gain was significant with olanzapine (mean +1 lb/mo). Sedation, confusion, and extrapyramidal symptoms were common across all antipsychotic groups.
- Mean age was 78 years, 56% female, MMSE ~15. About 60% had cholinesterase inhibitor use at baseline. The results fundamentally influenced clinical practice, discouraging routine use of antipsychotics for BPSD.
Study Design
- Study Type
- Multicenter, randomized, double-blind, placebo-controlled, pragmatic effectiveness trial
- Randomization
- Yes
- Blinding
- Double-blind; identical-appearing capsules for all groups
- Sample Size
- 421
- Follow-up
- Up to 36 weeks (phase 1)
- Centers
- 42
- Countries
- USA
Primary Outcome
Definition: Time to discontinuation of treatment for any reason (phase 1): Median 8.1 wk (olanzapine), 5.3 wk (quetiapine), 7.4 wk (risperidone), 8.0 wk (placebo); P=0.52
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| - | P=0.52 |
Citation
N Engl J Med 2006;355:1525-38