Sertraline for the treatment of depression in Alzheimer disease.
OBJECTIVE
Depression is common in Alzheimer disease (AD), and antidepressants are commonly used for its treatment, however, evidence for antidepressant efficacy in this population is lacking. The authors conducted a multicenter, randomized, placebo-controlled trial titled "Depression in Alzheimer's Disease-2" to assess the efficacy and tolerability of sertraline for depression in AD.


METHODS
One hundred thirty-one participants from five U.S. medical centers with mild-to-moderate AD (Mini-Mental State Examination scores 10-26) and depression of AD were randomized to double-blinded treatment with sertraline (N = 67) or placebo (N = 64), with a target dosage of 100 mg daily. Efficacy was assessed using logistic regressions and mixed effects models in an intention-to-treat analysis with imputation of missing data. Principal outcome measures were modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC), change in Cornell Scale for Depression in Dementia (CSDD) scores, and remission defined by both mADCS-CGIC score <or=2 and CSDD score <or=6.


RESULTS
mADCS-CGIC ratings (odd ratio [OR = 1.01], 95% confidence interval [CI]: 0.52-1.97, p = 0.98), CSDD scores (median difference at 12 weeks 1.2, 95% CI: 1.65-4.05, p = 0.41), and remission at 12 weeks of follow-up (OR = 2.06, 95% CI: 0.84-5.04, p = 0.11) did not differ between sertraline (N = 67) and placebo (N = 64). Sertraline-treated patients experienced more adverse events, most notably gastrointestinal and respiratory, than placebo-treated patients.


CONCLUSIONS
Sertraline did not demonstrate efficacy for the treatment depression symptoms in patients with AD. In addition, its use was associated with an increased incidence of adverse events. Thus, selective serotonin reuptake inhibitors may be of limited value for treating depression in patients with AD.
Rosenberg
Paul B
PB
Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. prosenb9@jhmi.edu
Drye
Lea T
LT
Martin
Barbara K
BK
Frangakis
Constantine
C
Mintzer
Jacobo E
JE
Weintraub
Daniel
D
Porsteinsson
Anton P
AP
Schneider
Lon S
LS
Rabins
Peter V
PV
Munro
Cynthia A
CA
Meinert
Curtis L
CL
Lyketsos
Constantine G
CG
D000368:Aged; D000544:Alzheimer Disease / Q000150:complications*; D003863:Depression / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D010352:Patient Dropouts / Q000706:statistics & numerical data; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D020280:Sertraline / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D016903:Drug Monitoring
D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline