Cognitive Effects of Atypical Antipsychotic Medications in Patients With Alzheimer's Disease: Outcomes From CATIE-AD
Publication: American Journal of Psychiatry
Abstract
Objective:
The impact of the atypical antipsychotics olanzapine, quetiapine, and risperidone on cognition in patients with Alzheimer's disease is unclear. The authors assessed the effects of time and treatment on neuropsychological functioning during the Clinical Antipsychotic Trials of Intervention Effectiveness–Alzheimer's Disease study (CATIE-AD).
Method:
CATIE-AD included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior who were randomly assigned to receive masked, flexible-dose olanzapine, quetiapine, risperidone, or placebo. Based on their clinicians' judgment, patients could discontinue the originally assigned medication and receive another randomly assigned medication. Patients were followed for 36 weeks, and cognitive assessments were obtained at baseline and at 12, 24, and 36 weeks. Outcomes were compared for 357 patients for whom data were available for at least one cognitive measure at baseline and one follow-up assessment that took place after they had been on their prescribed medication or placebo for at least 2 weeks.
Results:
Overall, patients showed steady, significant declines over time in most cognitive areas, including in scores on the Mini-Mental State Examination (MMSE; –2.4 points over 36 weeks) and the cognitive subscale of the Alzheimer's Disease Assessment Scale (–4.4 points). Cognitive function declined more in patients receiving antipsychotics than in those given placebo on multiple cognitive measures, including the MMSE, the cognitive subscale of the Brief Psychiatric Rating Scale, and a cognitive summary score summarizing change on 18 cognitive tests.
Conclusions:
In CATIE-AD, atypical antipsychotics were associated with worsening cognitive function at a magnitude consistent with 1 year's deterioration compared with placebo. Further cognitive impairment is an additional risk of treatment with atypical antipsychotics that should be considered when treating patients with Alzheimer's disease.
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History
Received: 18 December 2008
Revision received: 19 January 2010
Revision received: 18 February 2011
Accepted: 18 February 2011
Published online: 1 August 2011
Published in print: August 2011
Authors
Funding Information
Dr. Schneider has been a consultant for Pfizer, Eli Lilly, Johnson & Johnson, AstraZeneca, and Bristol-Myers Squibb. Dr. Keefe has received research support from AstraZeneca, Eli Lilly, and NIMH and has served as a consultant, adviser, or speaker for Abbott, Acadia, BiolineRx, Bristol-Myers Squibb, Cephalon, Cortex, Dainippon Sumitomo Pharma, Eli Lilly, Johnson & Johnson, Lundbeck, Memory Pharmaceuticals, Merck, Orexigen, Organon, Pfizer, Sanofi/Aventis, Schering-Plough, Wyeth, and Xenoport. Dr. Sano has served as a consultant or adviser for Aventis, Bayer, Bristol-Myers Squibb, Eisai, Elan, Forest, Genentech, GlaxoSmithKline, Janssen, Martek, Medivation, Novartis, Ortho-McNeil, Pfizer, Takeda, United BioSource, and Voyager. Dr. Sultzer has received research funding or lecture honoraria from or served as a consultant to AstraZeneca, Eli Lilly, Forest, and Pfizer. Dr. Lyketsos has received research funding, lecture honoraria, or travel support from or served as a consultant or adviser to Adlyfe, Associated Jewish Federation of Baltimore, AstraZeneca, Bristol-Myers Squibb, Eisai, Eli Lilly, Forest, GlaxoSmithKline, Ortho-McNeil, Monitor, Novartis, NIMH, National Institute on Aging, Pfizer, Supernus, Takeda, and Wyeth. Dr. Tariot has received research support or consulting or educational fees from Abbott, AC Immune, Alzheimer's Association, Arizona Department of Health Services, AstraZeneca, Avid, Baxter Healthcare, Eisai, Elan, Epix, Forest, GlaxoSmithKline, Institute for Mental Health Research, Lundbeck, Memory, Merck, Merz, Mitsubishi Pharma, Myriad, National Institute on Aging, Neurochem, NIMH, Ono, Pfizer, Sanofi-Aventis, Takeda, and Wyeth; he is also a contributor to the patent “Biomarkers of Alzheimer's Disease.” Dr. Stroup has received speaking or consulting fees from Eli Lilly, Janssen, and Lundbeck. The other authors report no financial relationships with commercial interests.Supported in part by NIMH research contract N01 MH-9001, USC Alzheimer's Disease Research Center NIH P50 AG05142, and the Department of Veterans Affairs. Medications for this study were provided by AstraZeneca, Forest, Janssen, and Eli Lilly.
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