Treating depression in Alzheimer disease: Efficacy and safety of sertraline therapy, and the benefits of depression reduction: The DIADS

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Abstract

Context: Major depression affects about 25% of the patients who have Alzheimer disease and has serious adverse consequences for patients and caregivers. Results of prior antidepressant treatment studies have produced contradictory findings and have not fully assessed the benefits of depression reduction. Objectives: To assess the efficacy and safety of sertraline hydrochloride for the treatment of major depression in Alzheimer disease, and to evaluate the effect of depression reduction on activities of daily living, cognition, and nonmood behavioral disturbance. Design: Randomized, placebo-controlled, parallel, 12-week, flexible-dose clinical trial with a 1-week, single-blind placebo phase. The study was conducted between January 1, 1998, and July 19, 2001. Setting: University outpatient clinic. Participants: Forty-four outpatients who have probable Alzheimer disease and major depressive episodes. Intervention: Sertraline hydrochloride, mean dosage of 95 mg/d, or identical placebo, randomly assigned. Main Outcome Measures: Response rate, Cornell Scale for Depression in Dementia, Hamilton Depression Rating Scale, Mini-Mental State Examination, Psychogeriatric Depression Rating Scale-activities of daily living subscale, and Neuropsychiatric Inventory to quantify patient behavior disturbance and caregiver distress. Results: In the sertraline-treated group 9 patients (38%) were full responders and 11 (46%) were partial responders compared with 3 (20%) and 4 (15%), respectively, in the placebo-treated group (P=.007). The sertraline-treated group had greater improvements in the scores for the Comell Scale for Depression in Dementia (P=.002) and Hamilton Depression Rating Scale (P=.01), and a statistical trend toward less decline in activities of daily living on the Psychogeriatric Depression Rating Scale-activities of daily living subscale (P=.07). There was no difference between the treatment groups in Mini-Mental State Examination (P=.22) or Neuropsychiatric Inventory (P=.32) ratings over time. When full responders, partial responders, and nonresponders were compared, full responders only, or full and partial responders had significantly better ratings on activities of daily living (P =.04), behavioral disturbance (P=.01), and caregiver distress (P=.006), but not on the Mini-Mental State Examination (P=.76). Safety monitoring indicated few differences in adverse effects between the 2 treatment groups. Conclusions: Sertraline is superior to placebo for the treatment of major depression in Alzheimer disease. Depression reduction is accompanied by lessened behavior disturbance and improved activities of daily living, but not improved cognition.

Original languageEnglish (US)
Pages (from-to)737-746
Number of pages10
JournalArchives of General Psychiatry
Volume60
Issue number7
DOIs
StatePublished - Jul 1 2003

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Sertraline
Alzheimer Disease
Depression
Safety
Activities of Daily Living
Placebos
Therapeutics
Caregivers
Geriatric Psychiatry
Cognition
Dementia
Equipment and Supplies
Ambulatory Care Facilities
Antidepressive Agents
Outpatients

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

@article{ba87708885b74a4e96e63a954dadb082,
title = "Treating depression in Alzheimer disease: Efficacy and safety of sertraline therapy, and the benefits of depression reduction: The DIADS",
abstract = "Context: Major depression affects about 25{\%} of the patients who have Alzheimer disease and has serious adverse consequences for patients and caregivers. Results of prior antidepressant treatment studies have produced contradictory findings and have not fully assessed the benefits of depression reduction. Objectives: To assess the efficacy and safety of sertraline hydrochloride for the treatment of major depression in Alzheimer disease, and to evaluate the effect of depression reduction on activities of daily living, cognition, and nonmood behavioral disturbance. Design: Randomized, placebo-controlled, parallel, 12-week, flexible-dose clinical trial with a 1-week, single-blind placebo phase. The study was conducted between January 1, 1998, and July 19, 2001. Setting: University outpatient clinic. Participants: Forty-four outpatients who have probable Alzheimer disease and major depressive episodes. Intervention: Sertraline hydrochloride, mean dosage of 95 mg/d, or identical placebo, randomly assigned. Main Outcome Measures: Response rate, Cornell Scale for Depression in Dementia, Hamilton Depression Rating Scale, Mini-Mental State Examination, Psychogeriatric Depression Rating Scale-activities of daily living subscale, and Neuropsychiatric Inventory to quantify patient behavior disturbance and caregiver distress. Results: In the sertraline-treated group 9 patients (38{\%}) were full responders and 11 (46{\%}) were partial responders compared with 3 (20{\%}) and 4 (15{\%}), respectively, in the placebo-treated group (P=.007). The sertraline-treated group had greater improvements in the scores for the Comell Scale for Depression in Dementia (P=.002) and Hamilton Depression Rating Scale (P=.01), and a statistical trend toward less decline in activities of daily living on the Psychogeriatric Depression Rating Scale-activities of daily living subscale (P=.07). There was no difference between the treatment groups in Mini-Mental State Examination (P=.22) or Neuropsychiatric Inventory (P=.32) ratings over time. When full responders, partial responders, and nonresponders were compared, full responders only, or full and partial responders had significantly better ratings on activities of daily living (P =.04), behavioral disturbance (P=.01), and caregiver distress (P=.006), but not on the Mini-Mental State Examination (P=.76). Safety monitoring indicated few differences in adverse effects between the 2 treatment groups. Conclusions: Sertraline is superior to placebo for the treatment of major depression in Alzheimer disease. Depression reduction is accompanied by lessened behavior disturbance and improved activities of daily living, but not improved cognition.",
author = "Lyketsos, {Constantine G} and Lourdes DelCampo and Steinberg, {Martin I} and Samus, {Quincy Miles} and Steele, {Cynthia D.} and Cynthia Munro and Baker, {Alva S.} and Leoutsakos, {Jeannie-Marie S} and Constantine Frangakis and Jason Brandt and Rabins, {Peter V}",
year = "2003",
month = "7",
day = "1",
doi = "10.1001/archpsyc.60.7.737",
language = "English (US)",
volume = "60",
pages = "737--746",
journal = "JAMA Psychiatry",
issn = "2168-622X",
publisher = "American Medical Association",
number = "7",

}

TY - JOUR

T1 - Treating depression in Alzheimer disease

T2 - Efficacy and safety of sertraline therapy, and the benefits of depression reduction: The DIADS

AU - Lyketsos, Constantine G

AU - DelCampo, Lourdes

AU - Steinberg, Martin I

AU - Samus, Quincy Miles

AU - Steele, Cynthia D.

AU - Munro, Cynthia

AU - Baker, Alva S.

AU - Leoutsakos, Jeannie-Marie S

AU - Frangakis, Constantine

AU - Brandt, Jason

AU - Rabins, Peter V

PY - 2003/7/1

Y1 - 2003/7/1

N2 - Context: Major depression affects about 25% of the patients who have Alzheimer disease and has serious adverse consequences for patients and caregivers. Results of prior antidepressant treatment studies have produced contradictory findings and have not fully assessed the benefits of depression reduction. Objectives: To assess the efficacy and safety of sertraline hydrochloride for the treatment of major depression in Alzheimer disease, and to evaluate the effect of depression reduction on activities of daily living, cognition, and nonmood behavioral disturbance. Design: Randomized, placebo-controlled, parallel, 12-week, flexible-dose clinical trial with a 1-week, single-blind placebo phase. The study was conducted between January 1, 1998, and July 19, 2001. Setting: University outpatient clinic. Participants: Forty-four outpatients who have probable Alzheimer disease and major depressive episodes. Intervention: Sertraline hydrochloride, mean dosage of 95 mg/d, or identical placebo, randomly assigned. Main Outcome Measures: Response rate, Cornell Scale for Depression in Dementia, Hamilton Depression Rating Scale, Mini-Mental State Examination, Psychogeriatric Depression Rating Scale-activities of daily living subscale, and Neuropsychiatric Inventory to quantify patient behavior disturbance and caregiver distress. Results: In the sertraline-treated group 9 patients (38%) were full responders and 11 (46%) were partial responders compared with 3 (20%) and 4 (15%), respectively, in the placebo-treated group (P=.007). The sertraline-treated group had greater improvements in the scores for the Comell Scale for Depression in Dementia (P=.002) and Hamilton Depression Rating Scale (P=.01), and a statistical trend toward less decline in activities of daily living on the Psychogeriatric Depression Rating Scale-activities of daily living subscale (P=.07). There was no difference between the treatment groups in Mini-Mental State Examination (P=.22) or Neuropsychiatric Inventory (P=.32) ratings over time. When full responders, partial responders, and nonresponders were compared, full responders only, or full and partial responders had significantly better ratings on activities of daily living (P =.04), behavioral disturbance (P=.01), and caregiver distress (P=.006), but not on the Mini-Mental State Examination (P=.76). Safety monitoring indicated few differences in adverse effects between the 2 treatment groups. Conclusions: Sertraline is superior to placebo for the treatment of major depression in Alzheimer disease. Depression reduction is accompanied by lessened behavior disturbance and improved activities of daily living, but not improved cognition.

AB - Context: Major depression affects about 25% of the patients who have Alzheimer disease and has serious adverse consequences for patients and caregivers. Results of prior antidepressant treatment studies have produced contradictory findings and have not fully assessed the benefits of depression reduction. Objectives: To assess the efficacy and safety of sertraline hydrochloride for the treatment of major depression in Alzheimer disease, and to evaluate the effect of depression reduction on activities of daily living, cognition, and nonmood behavioral disturbance. Design: Randomized, placebo-controlled, parallel, 12-week, flexible-dose clinical trial with a 1-week, single-blind placebo phase. The study was conducted between January 1, 1998, and July 19, 2001. Setting: University outpatient clinic. Participants: Forty-four outpatients who have probable Alzheimer disease and major depressive episodes. Intervention: Sertraline hydrochloride, mean dosage of 95 mg/d, or identical placebo, randomly assigned. Main Outcome Measures: Response rate, Cornell Scale for Depression in Dementia, Hamilton Depression Rating Scale, Mini-Mental State Examination, Psychogeriatric Depression Rating Scale-activities of daily living subscale, and Neuropsychiatric Inventory to quantify patient behavior disturbance and caregiver distress. Results: In the sertraline-treated group 9 patients (38%) were full responders and 11 (46%) were partial responders compared with 3 (20%) and 4 (15%), respectively, in the placebo-treated group (P=.007). The sertraline-treated group had greater improvements in the scores for the Comell Scale for Depression in Dementia (P=.002) and Hamilton Depression Rating Scale (P=.01), and a statistical trend toward less decline in activities of daily living on the Psychogeriatric Depression Rating Scale-activities of daily living subscale (P=.07). There was no difference between the treatment groups in Mini-Mental State Examination (P=.22) or Neuropsychiatric Inventory (P=.32) ratings over time. When full responders, partial responders, and nonresponders were compared, full responders only, or full and partial responders had significantly better ratings on activities of daily living (P =.04), behavioral disturbance (P=.01), and caregiver distress (P=.006), but not on the Mini-Mental State Examination (P=.76). Safety monitoring indicated few differences in adverse effects between the 2 treatment groups. Conclusions: Sertraline is superior to placebo for the treatment of major depression in Alzheimer disease. Depression reduction is accompanied by lessened behavior disturbance and improved activities of daily living, but not improved cognition.

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U2 - 10.1001/archpsyc.60.7.737

DO - 10.1001/archpsyc.60.7.737

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JO - JAMA Psychiatry

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