Alzheimer's Disease, Depression
Conditions
Keywords
Alzheimer's disease, Depression
Brief summary
The purpose of this study is to learn whether treating individuals with Alzheimer's disease and depression with the anti-depressant medication sertraline (Zoloft) is helpful to people with Alzheimer's disease and to their families and caregivers.
Detailed description
Participants are randomly assigned to treatment with sertraline (range 25-125 mg per day) or identical placebo for 24 weeks. There are 8 scheduled in-person visits in the 24 weeks. Visits include neuropsychological testing. Caregivers are asked to are the patient on a Daily Affect Diary for 6 weeks during the study period. Telephone followup is done at weeks 36 and 48. Both groups receive caregiver support/education.
Interventions
Sertraline: range of 25 to 125 mg per day for 24 weeks
DRUGPlacebo
Placebo designed to mimic sertraline taken daily for 24 weeks
Sponsors
National Institute of Mental Health (NIMH)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion: * Ability of the participant, caregiver or surrogate to provide written informed consent. * Dementia due to Alzheimer's disease * Stable treatment for Alzheimer's disease * Ability for the participant's caregiver to accompany the participant to study visits and participate in the study. Exclusion * Presence of a brain disease that might otherwise explain the presence of dementia * Clinically significant hallucinations or delusions * Current treatment of antipsychotics, anticonvulsants, and other antidepressants, benzodiazepines, or other psychotropic medications * Need for hospitalization or residence in a nursing facility
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) | Measured at Week 12 | At each study visit, based on patient examination and caregiver interview, clinicians rated overall impression of clinical change from baseline using the modified Alzheimer's Disease Cooperative Study Clinical Global Impression of Change index (mADCS-CGIC), which in addition to the original scale incorporates a global rating of mood and associated symptoms of depression. The mADCS-CGIC uses a seven-point Likert scale, with scores ranging from 1 (much better) to 7 (much worse), with a score of 4 being no change. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Remission According to Cornell Scale for Depression in Dementia Scale | Measured at Weeks 12 | The Cornell Scale for Depression in Dementia (CSDD), a 19-item scale measuring the severity of depression in dementia, utilizing input from both the caregiver and the participant. CSDD scores were imputed for 2 participants for week 2, 4 participants for week 4, 7 participants for week 8, and 12 participants for week 12. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from memory clinics at five academic centers in the United States.
Participants by arm
| Arm | Count |
|---|---|
| Sertraline Participants will receive sertraline at a target dose of 100mg daily.
Sertraline (Zoloft): Sertraline: range of 25 to 125 mg per day for 24 weeks | 67 |
| Placebo Participants will receive placebo matched to sertraline
Placebo: Placebo designed to mimic sertraline taken daily for 24 weeks | 64 |
| Total | 131 |
Baseline characteristics
| Characteristic | Sertraline | Placebo | Total |
|---|---|---|---|
| Age, Customized Age | 76.5 years STANDARD_DEVIATION 8 | 78.2 years STANDARD_DEVIATION 8 | 77.3 years STANDARD_DEVIATION 8 |
| Sex/Gender, Customized Female | 40 participants | 31 participants | 71 participants |
| Sex/Gender, Customized Male | 27 participants | 33 participants | 60 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 67 | 26 / 64 |
| serious Total, serious adverse events | 13 / 67 | 7 / 64 |
Outcome results
Primary
Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC)
At each study visit, based on patient examination and caregiver interview, clinicians rated overall impression of clinical change from baseline using the modified Alzheimer's Disease Cooperative Study Clinical Global Impression of Change index (mADCS-CGIC), which in addition to the original scale incorporates a global rating of mood and associated symptoms of depression. The mADCS-CGIC uses a seven-point Likert scale, with scores ranging from 1 (much better) to 7 (much worse), with a score of 4 being no change.
Time frame: Measured at Week 12
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sertraline | Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) | a bit worse | 6 participants |
| Sertraline | Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) | a bit better | 18 participants |
| Sertraline | Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) | worse | 5 participants |
| Sertraline | Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) | better | 18 participants |
| Sertraline | Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) | no change | 10 participants |
| Sertraline | Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) | much better | 9 participants |
| Sertraline | Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) | much worse | 1 participants |
| Placebo | Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) | much better | 3 participants |
| Placebo | Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) | much worse | 0 participants |
| Placebo | Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) | worse | 2 participants |
| Placebo | Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) | a bit worse | 9 participants |
| Placebo | Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) | no change | 11 participants |
| Placebo | Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) | a bit better | 18 participants |
| Placebo | Modfied Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (mADCS-CGIC) | better | 21 participants |
Comparison: The statistical analyses compared data collected from the CGIC of participants who received sertraline who had a score equal to or better than the CGIC of participants who received the placebo intervention.p-value: 0.9895% CI: [0.52, 1.97]Chi-squared
Secondary
Remission According to Cornell Scale for Depression in Dementia Scale
The Cornell Scale for Depression in Dementia (CSDD), a 19-item scale measuring the severity of depression in dementia, utilizing input from both the caregiver and the participant. CSDD scores were imputed for 2 participants for week 2, 4 participants for week 4, 7 participants for week 8, and 12 participants for week 12.
Time frame: Measured at Weeks 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sertraline | Remission According to Cornell Scale for Depression in Dementia Scale | 33 percentage of participants |
| Placebo | Remission According to Cornell Scale for Depression in Dementia Scale | 19 percentage of participants |
p-value: 0.1195% CI: [0.84, 5.04]Chi-squared