• Cognitive and functional performance measures: MATTIS Dementia Rating Scale, Folstein Mini-Mental, CDR, Apathy, EXIT, PASS, ISEL, SP-36, HAM-D, CIRS-G, NPI, McGill Pain Questionnaire, BSI, UKU, QWB, SCID [ Time Frame: Measured at Month 3 and Years 1 and 2 in maintenance ] [ Designated as safety issue: No ]
  

• Clinical measures: HRSD, Suicide Ideation Scale, UKU, PASS, SF-36, ISEL, NPI, McGill Pain Questionnaire, CIRS-G [ Time Frame: Measured at each study visit ] [ Designated as safety issue: No ]
  
• Functional status: PASS, Keitel Function Test; Late-Life Function and Disability Instrument, QWB [ Time Frame: Measured at baseline, entry into maintenance, and Month 3 and Years 1 and 2 in maintenance ] [ Designated as safety issue: No ]
  
• MRI, Antidepressant Treatment History Form [ Time Frame: Measured once ] [ Designated as safety issue: Yes ]
  

The purpose of this research study is to learn if combining an antidepressant medication (escitalopram, venlafaxine, or duloxetine) with a medication used in Alzheimer's Disease (donepezil), in elderly patients age 65 and older with major depression, will help to 1) improve and/or maintain memory, concentration, attention, and problem solving abilities such as ability to balance a checkbook, pay bills, use the telephone, and 2) reduce the risk of depressive symptoms from returning. Study participation will last up to two years.

We aim to investigate pharmacologic strategies for improving and stabilizing cognitive functioning in late-life depression and minimizing progression of cognitive and associated functional impairment. Cognitive impairment in late-life depression has not been adequately addressed in previous intervention research, is a core feature of the illness, contributes markedly to disability and impaired quality of life, and is an overlooked but potentially critical target of intervention. Data from the MTLD II study suggest that treating depression does not normalize cognitive functions and may not prevent their progression. We will test a pharmacologic strategy involving the cholinesterase inhibitor donepezil, in combination with maintenance antidepressant pharmacotherapy (escitalopram, venlafaxine, or duloxetine), to improve and to maintain cognitive functioning and functional competence in elderly patients with major depression.

We hypothesize that maintenance antidepressant pharmacotherapy combined with donepezil will be superior to maintenance antidepressant pharmacotherapy combined with placebo/clinical management in (1) improving cognitive performance; and (2) slowing progression of cognitive impairment and decline in functional competence. We plan to recruit 200 patients aged 65 and above in current episodes of major depression. Those who respond to antidepressant pharmacotherapy with citalopram, venlafaxine, or duloxetine will then be randomly assigned on a double-blind basis to one of two 24-month treatments: 1)antidepressant pharmacotherapy plus donepezil/clinical management; or 2)antidepressant pharmacotherapy plus placebo/clinical management.