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

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.

Figure 1

Flow diagram of patient treatment stratification during the trial. * 2 patients dropped during Phase A and thus were excluded from Phase B analysis. ** 6 patients who had been assigned to donepezil during Phase B chose not to contuinue donepezil treatment during Phase C and thus were excluded form the Phases B + C analysis. *** 3 patients who had been assigned to placebo during Phase B chose to begin donepezil treatment during Phase C and thus were excluded form the Phases B + C analysis.

Figure 2

Change in SRT Immediate recall during the donepezil vs no-donepezil treatment.