New approaches in education and health sciences management

New approaches in education and health sciences management

Evaluation of the Effect of Adding Donepezil to Sertraline in the Treatment of Major Depressive Disorder: A Double-Blind Randomized Clinical Trial

Document Type : Original Article

Authors
Seyed Davoud Hosseini Talari 1
Samaneh Farnia 2
Narjes Hendouei 3
Jamshid Yazdani Charati 4
1 Assistant Professor of Psychosomatic Medicine, Department of Psychiatry, School of Medicine, Ayatollah Rouhani Hospital, Babol University of Medical Sciences, Babol, Iran
2 Associate Proffessor of Psychiatry, Department of Psychiatry, School of Medicine AND Psychiatry and Behavioral Sciences Research Center, Addiction Institute, Mazandaran University of Medical Sciences.
3 Associate Professor of clinical pharmacy , Department of Pharmacotherapy, Faculty of Pharmacy and Psychiatry and Behavioral Sciences Research Center, Addiction Institute, Mazandaran University of Medical Sciences: Sari, IR
4 Professor of Biostatistics, Department of Biostatistics and Epidemiology, School of Health Health Sciences Research Center Addiction Institute Mazandaran University of Medical Sciences, Mazandaran, Iran. Psychiatry and Behavioral Sciences Research Ce
10.22034/edus.2025.236564
Abstract
Introduction: There are limited reports regarding the use of donepezil in the treatment of depression in the absence of cognitive disorders. Therefore, the aim of this study was to investigate the effect of donepezil on depressive symptoms and memory impairment in patients with major depressive disorder.
Materials and Methods: In this study, 40 patients diagnosed with major depressive disorder were randomly assigned to two groups. The first group received sertraline plus placebo, and the second group received sertraline plus donepezil for a period of three months. After three months of combination therapy, sertraline was continued at the same previous dose, while placebo and donepezil were discontinued. Data were collected using the Hamilton Depression Rating Scale (HDRS) and the Wechsler Memory Scale before treatment, during combination therapy, and after treatment.
Results: Repeated-measures analysis in the two intervention groups showed no significant difference in the reduction of depression scores between the groups during treatment up to the third month. Only at the sixth month after initiation of treatment (three months after discontinuation of donepezil and placebo), the depression score increased in the sertraline-plus-placebo group compared with the third month, resulting in a statistically significant difference in depression score reduction between the two intervention groups. In both groups—sertraline plus placebo and sertraline plus donepezil—the memory test scores showed a significant increase three months after the initiation of treatment. However, at the sixth month (three months after discontinuation of donepezil and placebo), the memory test score in the placebo group showed no significant difference compared with baseline, whereas in the donepezil group it remained significantly higher than before treatment.
Conclusion: Overall, the improvement in depressive symptoms and memory function was more sustained when donepezil was administered in combination with antidepressant medication.
Keywords
Depression
Cognitive Disorder
Cholinesterase Inhibitor
Donepezil

IRCT Registration Number: IRCT2013031011885N2

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New approaches in education and health sciences management
Volume 3, Issue 1
april 2026
Spring 2026
Pages 12-23

  • Receive Date 04 September 2025
  • Revise Date 08 November 2025
  • Accept Date 10 January 2026
  • First Publish Date 10 January 2026
  • Publish Date 21 March 2026