Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.


METHODS
University outpatient clinic.


METHODS
Forty-four outpatients who have probable Alzheimer disease and major depressive episodes.


METHODS
Sertraline hydrochloride, mean dosage of 95 mg/d, or identical placebo, randomly assigned.


METHODS
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 Cornell 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.
Lyketsos
Constantine G
CG
Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA. kostas@jhmi.edu
DelCampo
Lourdes
L
Steinberg
Martin
M
Miles
Quincy
Q
Steele
Cynthia D
CD
Munro
Cynthia
C
Baker
Alva S
AS
Sheppard
Jeannie-Marie E
JM
Frangakis
Constantine
C
Brandt
Jason
J
Rabins
Peter V
PV
D000203:Activities of Daily Living / Q000523:psychology; D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000453:epidemiology* / Q000523:psychology; D000553:Ambulatory Care; D017028:Caregivers / Q000523:psychology; D003072:Cognition Disorders / Q000175:diagnosis / Q000523:psychology; D015897:Comorbidity; D003866:Depressive Disorder / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology; D004334:Drug Administration Schedule; D005260:Female; D015577:Geriatric Assessment; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis / Q000523:psychology; D009483:Neuropsychological Tests; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use*; D016037:Single-Blind Method; D016896:Treatment Outcome
D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline