Clinical trial NCT00009191: The Depression in Alzheimer's Disease Study (DIADS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Alzheimer Disease
Depression
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2001-01-24
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
Study officials:
References:
citation: Lyketsos CG, Sheppard JM, Steele CD, Kopunek S, Steinberg M, Baker AS, Brandt J, Rabins PV. Randomized, placebo-controlled, double-blind clinical trial of sertraline in the treatment of depression complicating Alzheimer's disease: initial results from the Depression in Alzheimer's Disease study. Am J Psychiatry. 2000 Oct;157(10):1686-9. doi: 10.1176/appi.ajp.157.10.1686.