A randomized, placebo-controlled study of the efficacy and safety of sertraline in the treatment of the behavioral manifestations of Alzheimer's disease in outpatients treated with donepezil.
OBJECTIVE
To examine the safety and efficacy of sertraline augmentation therapy in the treatment of behavioral manifestations of Alzheimer's disease (AD) in outpatients treated with donepezil.


METHODS
Patients with probable or possible AD, and a Neuropsychiatric Inventory (NPI) total score >5 (with a severity score > or =2 in at least one domain), were treated with donepezil (5-10 mg) for 8 weeks, then randomly assigned to 12 weeks of double-blind augmentation therapy with either sertraline (50-200 mg) or placebo. Primary efficacy measures were the 12-item Neuropsychiatric Inventory (NPI) and the Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S) scales.


RESULTS
24 patients were treated with donepezil+sertraline and 120 patients with donepezil+placebo. There were no statistically significant differences at endpoint on any of the three primary efficacy measures. However, a linear mixed model analysis found modest but statistically significantly greater improvements in the CGI-I score on donepezil+sertraline. Moreover, in a sub-group of patients with moderate-to-severe behavioral and psychological symptoms of dementia, 60% of patients on sertraline vs 40% on placebo (p = 0.006) achieved a response (defined as > or = 50% reduction in a four-item NPI-behavioral subscale). One adverse event (diarrhea) was significantly (p < 0.05) more common in the donepezil+sertraline group compared to the donepezil+placebo group.


CONCLUSIONS
Sertraline augmentation was well-tolerated in this sample of AD outpatients. In addition, post hoc analyses demonstrated a modest but statistically significant advantage of sertraline over placebo augmentation in mixed model analyses and a clinically and statistically significant advantage in a subgroup of patients with moderate-to-severe behavioral and psychological symptoms of dementia.
Finkel
Sanford I
SI
Department of Psychiatry, University of Chicago Medical School, and the Leonard Schanfield Research Institute at Council for Jewish Elderly, Chicago, IL 60091, USA. sfinkel104@aol.com
Mintzer
Jacobo E
JE
Dysken
Maurice
M
Krishnan
K R R
KR
Burt
Tal
T
McRae
Thomas
T
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D000553:Ambulatory Care / Q000379:methods; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001526:Behavioral Symptoms / Q000188:drug therapy* / Q000209:etiology; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D000077265:Donepezil; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D020280:Sertraline / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000928:Antidepressive Agents; D002800:Cholinesterase Inhibitors; D000077265:Donepezil; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline