期刊
ARCHIVES OF GENERAL PSYCHIATRY
卷 68, 期 1, 页码 51-60出版社
AMER MEDICAL ASSOC
DOI: 10.1001/archgenpsychiatry.2010.184
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资金
- Forest Laboratories
- Pfizer/Eisai
- Bristol-Myers Squibb
- Wyeth
- Eli Lilly and Co
- Sandra A. Rotman Program and Chair
- Canadian Institutes of Health Research
- Pfizer
- Novartis
- Ortho-McNeil Neurologics
- National Institutes of Health [R01 AG022462, R21AG033387, K01 EB009724, R49CE001495, R01 MH043823, R01 MH037869, P30 MH071944, P50 AG05133, AG030653, R01MH072947]
- Forest Research Institute
- Janssen Research Institute
- Duke Endowment
- Guardian Angel Thrift Fund
- North Carolina Translational Research Center
- US Administration on Aging
- Elan
- Myriad
- Neurochem
- GlaxoSmithKline
- UPMC Endowed Chair in Geriatric Psychiatry
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [KL2TR000146, UL1TR000005] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR INJURY PREVENTION AND CONTROL [R49CE001495] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [K01EB009724] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH037869, P30MH071944, R01MH043832, R01MH083660, R01MH043823, R01MH072947] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [P50AG005133, R01AG022462, R01AG030653, R21AG033387] Funding Source: NIH RePORTER
Context: Cognitive impairment in late-life depression is a core feature of the illness. Objective: To test whether donepezil hydrochloride and antidepressant therapyis superior to placebo and antidepressant therapy in improving cognitive performance and instrumental activities of daily living and in reducing recurrences of depression over 2 years of maintenance treatment. Design: Randomized, double-blind, placebo-controlled maintenance trial. Setting: University clinic. Participants: One hundred thirty older adults aged 65 years and older with recently remitted major depression. Interventions: Random assignment to maintenance antidepressant pharmacotherapy and donepezil or to maintenance antidepressant pharmacotherapy and placebo. Main Outcome Measures: Global neuropsychological performance, cognitive instrumental activities of daily living, and recurrent depression. Results: Donepezil and antidepressant therapy temporarily improved global cognition ( treatment x time interaction, F-2,F-126=3.78; P=.03), but effect sizes were small (Cohen d=0.27, group difference at 1 year). A marginal benefit to cognitive instrumental activities of daily living was also observed ( treatment X time interaction, F-2,F-137=2.94; P=.06). The donepezil group was more likely than the placebo group to experience recurrent major depression (35% [95% confidence interval {CI}, 24%-46%] vs 19% [ 95% CI, 9%-29%], respectively; log-rank chi(2)=3.97; P=.05; hazard ratio=2.09 [ 95% CI, 1.00-4.41]). Post hoc subgroup analyses showed that of 57 participants with mild cognitive impairment, 3 of 30 participants (10% [ 95% CI, 0%-21%]) receiving donepezil and 9 of 27 participants (33% [ 95% CI, 16%-51%]) receiving placebo had a conversion to dementia over 2 years ( Fisher exact test, P=.05). The mild cognitive impairment subgroup had recurrence rates of major depression of 44% with donepezil vs 12% with placebo ( likelihood ratio=4.91; P=.03). The subgroup with normal cognition (n=73) showed no benefit with donepezil and no increase in recurrence of major depression. Conclusions: Whether a cholinesterase inhibitor should be used as augmentation in the maintenance treatment of late-life depression depends on a careful weighing of risks and benefits in those with mild cognitive impairment. In cognitively intact patients, donepezil appears to have no clear benefit for preventing progression to mild cognitive impairment or dementia or for preventing recurrence of depression.
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