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


CONCLUSIONS
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.
Pelton
Gregory H
GH
Late Life Depression Clinic, The Memory Disorders Center, and The Division of Geriatric Psychiatry, New York State Psychiatric Institute, NY, USA. ghp4@columbia.edu
Harper
Oliver L
OL
Tabert
Matthias H
MH
Sackeim
Harold A
HA
Scarmeas
Nikolaos
N
Roose
Steven P
SP
Devanand
D P
DP
D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy* / Q000523:psychology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D000077265:Donepezil; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use; D016896:Treatment Outcome
D000928:Antidepressive Agents; D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil; D020280:Sertraline