Randomized double-blind placebo-controlled donepezil augmentation in antidepressant-treated elderly patients with depression and cognitive impairment: a pilot study

Int J Geriatr Psychiatry. 2008 Jul;23(7):670-6. doi: 10.1002/gps.1958.

Abstract

Objective: To assess combined antidepressant and cognitive enhancer treatment in elderly patients presenting with depression plus cognitive impairment.

Methods: Twenty-three elderly (>50 years old) depressed, cognitively impaired (DEP-CI) patients participated in a pilot study. We evaluated whether, after 8 weeks of open antidepressant treatment, donepezil HCl (Aricept) would afford added cognitive benefit compared to placebo in a randomized 12-week trial. A subsample continued in an 8-month extension phase of open treatment with donepezil. Neuropsychological testing (NPT) was performed and antidepressant response monitored at baseline and the 8, 20, and 52-week time points.

Results: At 8-weeks, the antidepressant response rate was 61% (14/23). Improvement in SRT immediate recall (SRT-IR; e.g. episodic verbal memory) was observed in responders compared to non-responders. During the 12-week, placebo-controlled, donepezil add-on trial, patients on donepezil showed further improvement in SRT-IR versus patients on placebo. In the open extension phase, patients who continued open donepezil treatment (n = 6) maintained improvement in memory and tended to show an advantage over patients who never received donepezil and were evaluated at the 52-week time point (n = 6). There were no observed significant donepezil effects on non-memory cognitive domains.

Conclusion: These preliminary findings suggest that addition of a cholinesterase inhibitor (AChEI) following antidepressant medication treatment in elderly Dep-CI patients may improve cognition, and support the need for a confirmatory, larger randomized placebo-controlled trial.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antidepressive Agents / therapeutic use*
  • Cholinesterase Inhibitors / adverse effects
  • Cholinesterase Inhibitors / therapeutic use
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / psychology
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Donepezil
  • Epidemiologic Methods
  • Female
  • Humans
  • Indans / adverse effects
  • Indans / therapeutic use*
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Nootropic Agents / adverse effects
  • Nootropic Agents / therapeutic use*
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Sertraline / therapeutic use
  • Treatment Outcome

Substances

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