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Donepezil treatment of older adults with cognitive impairment and depression (DOTCODE study): clinical rationale and design


Pelton, Gregory H., Andrews, Howard, Roose, Steven P., Marcus, Sue M., D'Antonio, Kristina, Husn, Hala, Petrella, Jeffrey R., Zannas, Anthony S., Doraiswamy, P. Murali, Devanand, D. P.


Contemporary Clinical Trials, Volume: 37, No.: 2, Pages.: 200-208

Year of Publication



Treatment strategies for patients with depression and cognitive impairment (DEP-CI), who are at high risk to develop a clinical diagnosis of dementia, are not established. This issue is addressed in the donepezil treatment of cognitive impairment and depression (DOTCODE) pilot clinical trial. The DOTCODE study is the first long-term treatment trial that assesses differences in conversion to dementia and cognitive change in DEP-CI patients using a study design of open antidepressant medication plus add-on randomized, double-blind, placebo-controlled treatment with the acetylcholinesterase inhibitor donepezil. In Phase 1, DEP-CI patients receive optimized antidepressant treatment for 16 weeks. In Phase 2, antidepressant treatment is continued with the addition of randomized, double-blind treatment with donepezil or placebo. The total study duration for each patient is 78 weeks (18 months). Eighty DEP-CI outpatients (age 55 to 95 years) are recruited: 40 at New York State Psychiatric Institute/Columbia University and 40 at Duke University Medical Center. The primary outcome is conversion to a clinical diagnosis of dementia. The secondary outcomes are cognitive change scores in Selective Reminding Test (SRT) total recall and the modified Alzheimer’s Disease Assessment Scale (ADAS-cog). Other key assessments include the 24-item Hamilton Depression Rating Scale and antidepressant response; Clinical Global Impression (CGI) for depression, cognition, and global status; neuropsychological test battery for diagnosis; informant report of functional abilities (Pfeffer FAQ); and Treatment Emergent Symptom Scale (TESS) for somatic side effects. Apolipoprotein E ε4 status, odor identification deficits, and MRI entorhinal/hippocampal cortex atrophy at baseline are evaluated as neurobiological moderators of donepezil treatment effects.; Copyright © 2013 Elsevier Inc. All rights reserved.

Bibtex Citation

@article{Pelton_2014, doi = {10.1016/j.cct.2013.11.015}, url = {}, year = 2014, month = {mar}, publisher = {Elsevier {BV}}, volume = {37}, number = {2}, pages = {200--208}, author = {Gregory H. Pelton and Howard Andrews and Steven P. Roose and Sue M. Marcus and Kristina D{textquotesingle}Antonio and Hala Husn and Jeffrey R. Petrella and Anthony S. Zannas and P. Murali Doraiswamy and D.P. Devanand}, title = {Donepezil treatment of older adults with cognitive impairment and depression ({DOTCODE} study): Clinical rationale and design}, journal = {Contemporary Clinical Trials} }


activities of daily living, administration & dosage, aged, aged, 80 and over, aging, alzheimer disease, alzheimer’s disease, antidepressants, antidepressive agents, cholinesterase inhibitors, cognition, cognition disorders, cognitive impairment, depression, depressive disorder, donepezil, double-blind method, drug effects, drug therapy, female, humans, indans, magnetic resonance imaging, male, memory decline, middle aged, neuropsychological tests, piperidines, randomized clinical trial, research design, therapeutic use

Countries of Study


Types of Dementia

Dementia (general / unspecified), Mild Cognitive Impairment (MCI)

Types of Study

Randomised Controlled Trial

Type of Outcomes

Cognition, Depression and Anxiety


Specialist Dementia Centre Care / Memory Clinic

Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions

Anti-Alzheimer medications, e.g.: donezepil, galantamine, rivastigmine, memantime, Antipsychotics and antidepressants