Article Highlights
- •A long-term randomized trial of adjunctive donepezil for comorbid depression and cognitive impairment in 79 patients on stable antidepressant treatment.
- •No treatment group differences between donepezil and placebo on the cognitive outcome measures of ADAS-Cog, SRT total immediate recall, and FAQ.
- •Study results do not support the current common practice of adjunctive off-label cholinesterase inhibitor use in patients with comorbid depression and cognitive impairment.
Objective
Depression and cognitive impairment are often comorbid in older adults, but optimal
treatment strategies remain unclear. In a two-site study, the efficacy and safety
of add-on donepezil versus placebo were compared in depressed patients with cognitive
impairment receiving stable antidepressant treatment.
Methods
A randomized, double-blind, placebo-controlled trial was conducted in older adults
with depression and cognitive impairment (https://clinicaltrials.gov/ct2/show/NCT01658228; NCT01658228). Patients received open-label antidepressant treatment for 16 weeks,
initially with citalopram and then with venlafaxine, if needed, followed by random
assignment to add-on donepezil 5–10 mg daily or placebo for another 62 weeks. Outcome
measures were neuropsychological test performance (Alzheimer's Disease Assessment
Scale—Cognitive subscale [ADAS-Cog] and Selective Reminding Test [SRT] total immediate
recall) and instrumental activities of daily living (Functional Activities Questionnaire).
Results
Of 81 patients who signed informed consent, 79 patients completed the baseline evaluation.
Open antidepressant treatment was associated with improvement in depression in 63.93%
responders by week 16. In the randomized trial, there were no treatment group differences
between donepezil and placebo on dementia conversion rates, ADAS-Cog, SRT total immediate
recall, or FAQ. Neither baseline cognitive impairment severity nor apolipoprotein
E e4 genotype influenced donepezil efficacy. Donepezil was associated with more adverse
effects than placebo.
Conclusion
The results do not support adjunctive off-label cholinesterase inhibitor treatment
in patients with depression and cognitive impairment. The findings highlight the need
to prioritize discovery of novel treatments for this highly prevalent population with
comorbid illnesses.
Key Words
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Article info
Publication history
Published online: July 02, 2018
Accepted:
May 16,
2018
Received in revised form:
May 15,
2018
Received:
February 9,
2018
Identification
Copyright
© 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
