Objective: To review the primary literature regarding the use of cholinesterase inhibitors (ChEIs) as adjunctive therapy for cognitive enhancement and improvement of depressive symptoms for older adults with depression. Data Sources: A literature search of MEDLINE (1950-September 2011) was conducted, using the search term depression in combination with cholinesterase inhibitor, donepezil, galantamine, or rivastigmine. A search of reference citations was conducted to identify additional references. Study Selection and Data Extraction: English-language clinical trials were evaluated. Studies that included subjects with Alzheimer's disease, dementia, Parkinson disease, bipolar disorder, or schizophrenia were excluded. Four clinical studies met our criteria, Data Synthesis: We identified 4 randomized, double-blind, placebo-controlled trials that ranged in sample size from 20 to 130. Galantamine 16 mg daily was evaluated in 2 trials lasting 8 and 24 weeks. Neither study found a statistically significant difference in measures of cognition or Hamilton Rating Scale for Depression scores. Donepezil augmentation was evaluated in a 1-year and a 2-year trial. Donepezil was found to improve global cognition at 1 year, but the benefit did not persist at year 2. Subjects with mild cognitive impairment at baseline who received donepezil experienced higher depression recurrence than did those who took placebo (p = 0.03); this effect was not observed in cognitively intact subjects (p = 0.39). Conclusions: There is no clear benefit for ChEI therapy as an adjunct to antidepressant therapy for depressed older adults.
