Combination Treatment Study for Memory Impairment and Depression
Status:
Completed
Trial end date:
2016-01-01
Target enrollment:
Participant gender:
Summary
Patients presenting with depression (DEP) and cognitive impairment (CI), represent a unique,
understudied population that is difficult to diagnose, treat and estimate prognosis. Our
pilot data, supported by the literature, suggest that many DEP-CI patients show cognitive
decline and often convert to dementia, primarily Alzheimer's disease (AD). In DEP-CI, there
is a lack of data on treatment response of mood symptoms to antidepressant treatment and
particularly of cognitive deficits to cognitive enhancer treatment. Our initial pilot data in
a double-blind study showed that donepezil was superior to placebo in improving memory in
antidepressant-treated DEP-CI patients. In a second pilot study, open label es-citalopram
plus memantine treatment led to a low rate of conversion to dementia.
In this proposed pilot clinical trial, the investigators will evaluate, treat and follow a
broad sample of 80 DEP-CI patients at NYSPI/Columbia University Medical Center (N = 40) and
Duke University Medical Center (N = 40). Recruitment will be from clinics and/or
advertisements. In the treatment protocol, all 80 DEP-CI patients will receive baseline mood
and memory assessments and open antidepressant treatment with citalopram for 8 weeks. At 8
weeks, repeat assessment will occur and patients whose depression has responded to citalopram
will be randomized to add-on donepezil or placebo. Non-responders to citalopram will receive
open treatment with venlafaxine and will be randomized 8 weeks later (16 weeks of open
antidepressant treatment) to add-on donepezil or placebo. Patients will be followed for a
total period of 18 months with continuous open antidepressant treatment during the trial.
Donepezil is being studied in order to increase the likelihood of obtaining a signal. If the
results are positive, the investigators can begin clarifying the mechanism(s) in subsequent
trials. Baseline apolipoprotein E e4 genotype, odor identification deficits, and MRI
hippocampal and entorhinal cortex atrophy will be explored as predictors of donepezil
response in the 18-month trial. Improving cognition and delaying conversion to a clinical
diagnosis of dementia in this high risk group will enhance quality of life, reduce family
burden, and markedly diminish overall health care costs.