Combination Treatment Study for Memory Impairment and Depression

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.

Conditions

• Depression
• Mild Cognitive Impairment

Interventions

DRUG

Donepezil

Donepezil 5mg will be given for 6 weeks and if tolerated, the dose will be increased to 10 mg per day. The dose range of 5 to 10 mg per day is the recommended dose for donepezil in the treatment of mild to moderate Alzheimer's disease.

DRUG

Placebo

A placebo capsule will be given to randomized subjects for the starting at week 16 and continuing for the remainder of the study. This group will not receive donepezil as treatment.

DRUG

Citalopram

Citalopram tablet will be given to subjects during an 8 week flexible dosing open treatment. If subjects respond to citalopram treatment they will be randomized to add-on donepezil/placebo.

DRUG

Venlafaxine

Venlafaxine tablet will be given to subjects during an 8 week flexible dosing open treatment if they did not respond to citalopram. If subjects respond to venlafaxine treatment they will be randomized to add-on donepezil/placebo.

Sponsors & Collaborators

• National Institute on Aging (NIA)

  collaborator NIH

• New York State Psychiatric Institute

  lead OTHER

Principal Investigators

• Davangere Devanand, MD · Columbia University

• Gregory Pelton, MD · Columbia University

• Steven Roose, MD · Columbia University

• Murali Doraiswamy, MD · Duke University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

55 Years

Max Age

95 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-09-30

Primary Completion

2016-01-31

Completion

2016-01-31

Countries

• United States

Study Locations