Atypical antipsychotics worsen cognition in Alzheimer €™s (CATIE-AD)

Atypical antipsychotics worsen cognition in Alzheimer €™s (CATIE-AD)

Clinical question
Does the use of atypical antipsychotic medications in patients with Alzheimer’s disease affect cognitive function?
Bottom line
Atypical antipsychotics in patients with Alzheimer’s disease were associated with worse cognitive function (equivalent to a typical 1-year deterioration) than placebo. (LOE = 1b)
Reference
Vigen CL, Mack WJ, Keefe RS, et al. Cognitive effects of atypical antipsychotic medications in patients with Alzheimer €™s disease: Outcomes from CATIE-AD. Am J Psychiatry 2011;168(8):831-839. [PubMed ® Abstract]
Study design: Randomized controlled trial (double-blinded)
Funding Source: Government
Allocation: Concealed
Setting: Outpatient (specialty)
Synopsis
The Clinical Antipsychotic Trials of Intervention Effectiveness €“ Alzheimer €™s Disease (CATIE-AD) was a complex randomized controlled trial of 421 patients with Alzheimer €™s disease living at home or in an assisted living facility. It included multiple arms and phases and lasted for 36 weeks. In Phase 1, patients were assigned to olanzapine, quetapine, risperidone, or placebo with a 2:2:2:3 ratio. If the medication was stopped, the patient could be enrolled in Phase 2. In Phase 2, if the original medication was an atypical antipsychotic, the randomization was to citalopram, a different atypical antipsychotic, or placebo (3:3:2); if the original allocation was to placebo, randomization was to each of the atypical antipsychotics (3:1:1:1). If Phase 2 medication was discontinued, the patient could enter Phase 3 which was open-label randomization to any atypical not already assigned. The patient could enter Phase 4 at any point after initial randomization, which consisted of an observational phase in which the physician chose the open-label medication. Assessments occurred at 12, 24, and 36 weeks. Patients receiving any atypical antipsychotic for at least 2 weeks prior to assessment, had a mean decline of 2.67 points compared with 0.21 points for the placebo-treated patients on the Mini-Mental Status Examination (P = .004). However, for both groups the decline had a 95% confidence interval that included zero. The treated patients also showed significantly greater rates of decline in cognitive function on several other standardized measures than the control patients. Clinical global impression of change scores for the atypical group were actually better, although not statistically significant, which could be related to control of symptoms such as combativeness.
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