The Depression in Alzheimer's Disease Study (DIADS)

Sponsor

Johns Hopkins University (Other)

Overall Status

Completed

CT.gov ID

NCT00009191

Collaborator

National Institute of Mental Health (NIMH) (NIH)

Location

Duration (Months)

Study Details

Study Description

Brief Summary

Major depression afflicts approximately 25 percent of patients with AD. Depression in AD patients leads to mental suffering, behavioral disturbance (such as aggression), poor cognition, poor self-care, caregiver depression, caregiver burden, and early entry into the nursing home. Since major depression is treatable, this additional disability may be avoidable. The use of antidepressants to treat major depression in AD is supported by two studies, although a third does not show a benefit for antidepressants over placebo. Also, the safety of antidepressant treatment in depressed AD patients is poorly studied. A conclusive study showing that depression reduction in AD can be accomplished safely with antidepressant medications, and that depression reduction is associated with improvements in activities of daily living, non-mood behavioral disturbances, caregiver burden, and caregiver depression would have major clinical and cost implications for the care of the AD patient. This study is a 13-week, double blind, flexible dose, placebo controlled trial of sertraline in the treatment of outpatients with AD and co-morbid major depression. The hypothesis is that antidepressant treatment is superior to placebo in improving mood, in improving cognition, in reducing physical dependency, in reducing caregiver depression, and in reducing caregiver burden. It is also hypothesized that the degree of depression reduction is correlated with these improvements. It is further hypothesized that the safety profile of sertraline when compared to placebo is acceptable, especially with regard to risk of falls, sleep disturbance, and delirium. One hundred community residing outpatients with probable AD who also meet DSM-IV criteria for major depressive episode will be recruited into the study. They will be randomized to sertraline or placebo and followed through weekly telephone contact by an experienced clinical trials team. Outcomes will be assessed every 3 weeks, for a total of four followup data points. Scales assessing the following domains will be used: depression, cognition, behavioral disturbance, physical dependency, delirium, falls, sleep, other side effects, caregiver depression, caregiver burden, caregiver functioning, and caregiver health.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease Depression	Drug: Sertraline [Zoloft]	Phase 4

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Double

Primary Purpose:

Treatment

Study Start Date :

Nov 1, 2005

Actual Primary Completion Date :

Nov 1, 2006

Actual Study Completion Date :

Nov 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion:

Diagnosis of Probable Alzheimer's disease (AD) by NINCDS/ADRDA criteria (McKann et al., 1984), with a MMSE score greater than 10
Diagnosis of current major depressive episode (MD), by DSM-IV, based on the SCID-IV examination
Patients will be included even if they have a pre-AD history of unipolar depression
Patients who currently are being treated with antidepressants but continue to meet criteria for MD (i.e., have not responded to the medications) and who are willing to discontinue the other medication and enter the study also will be included
Currently residing in the community (own home,family member's home, or small group home) and agreeing to 13 weeks of followup in the study
Stable medical history and general health, in the opinion of the study psychiatrist
A caregiver who knows the patient well (spends at least 10 hours per week with him or her), and who is in reasonably good health, agrees to participate as well
Participant and his/her legal representative provide informed consent

Exclusion:

Use of sertraline is contraindicated, based on the Food and Drug Administration package insert for sertraline
Patient has a lifetime diagnosis of schizophrenia, bipolar disorder, or pre-AD anxiety disorder, as determined by the SCID
Patient has a current substance use disorder, as determined by the SCID
Patient is acutely suicidal or requires inpatient psychiatric hospitalization, as determined by the study psychiatrist
No psychotropic medicine dose changes, including cholinesterase inhibitors, after study entry
May enter with any drug except another antidepressant.