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

Int J Geriatr Psychiatry. 2004 Jan;19(1):9-18. doi: 10.1002/gps.998.

Abstract

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 and materials: 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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / psychology
  • Ambulatory Care / methods
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use*
  • Behavioral Symptoms / drug therapy*
  • Behavioral Symptoms / etiology
  • Cholinesterase Inhibitors / therapeutic use
  • Donepezil
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Indans / therapeutic use
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Nootropic Agents / therapeutic use
  • Piperidines / therapeutic use
  • Psychiatric Status Rating Scales
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Sertraline / adverse effects
  • Sertraline / therapeutic use*
  • Treatment Outcome

Substances

  • Antidepressive Agents
  • Cholinesterase Inhibitors
  • Indans
  • Nootropic Agents
  • Piperidines
  • Serotonin Uptake Inhibitors
  • Donepezil
  • Sertraline