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Maryam Shahrokhi1 
, Robabeh Soleimani2 , Mahdi Ahmadinia3 , AmirMahdi Rezapour4 , Saeed Taatirad2 , Faezeh Jamali5 , Hamed Jafari Mohamadabadi6 , Roja Qobadighadikolaei *7
, Robabeh Soleimani2 , Mahdi Ahmadinia3 , AmirMahdi Rezapour4 , Saeed Taatirad2 , Faezeh Jamali5 , Hamed Jafari Mohamadabadi6 , Roja Qobadighadikolaei *7
1- Department of Clinical Pharmacy, Faculty of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran
2- Department of Psychiatry, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
3- Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
4- Student Research Committee, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran
5- Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
6- Department of Psychiatry, Psychosis Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
7- Department of Clinical Pharmacy, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
2- Department of Psychiatry, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
3- Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
4- Student Research Committee, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran
5- Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
6- Department of Psychiatry, Psychosis Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
7- Department of Clinical Pharmacy, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
Abstract:
Background: Bipolar disorder (BD) is frequently treated with electroconvulsive therapy (ECT), which, despite its efficacy in severe mood episodes, is often complicated by cognitive impairment. To our knowledge, no standard prophylactic therapy currently exists to prevent these adverse effects. Melatonin, with established antioxidant and neuroprotective properties, may attenuate ECT-related cognitive dysfunction.
Methods: In this randomized, double-blind, placebo-controlled trial, 46 inpatients with BD undergoing ECT were allocated 1:1 to receive either melatonin (3 mg nightly) or identical placebo capsules. Study medication was administered from 24 h before the first ECT session until 24 h after the final session. Cognitive outcomes were assessed using the Mini-Mental State Examination (MMSE) and its subdomains at baseline and after each ECT session. Secondary outcomes included systolic and diastolic blood pressure. Adverse events were recorded throughout the trial.
Results: Compared with placebo, melatonin significantly improved global cognition across the ECT course (group × time interaction, p=0.021). At the final session, patients receiving melatonin demonstrated higher MMSE scores (27.9 ± 1.8 vs. 26.5 ± 2.0), with the strongest improvements in recall (+0.6 points, p=0.012) and attention/calculation (+0.5 points, p=0.018). Blood pressure (BP) values remained stable (ΔSBP: –1.2 ± 3.1 mmHg melatonin vs. –0.8 ± 2.9 mmHg placebo, p=0.64), and melatonin was also well tolerated.
Conclusion: Adjunctive melatonin reduced ECT-related cognitive impairment in BD patients, with pronounced benefits in memory and attention, while maintaining an excellent safety profile. These findings support melatonin as a simple, inexpensive, and widely accessible therapeutic option to support cognition in this vulnerable population.
Methods: In this randomized, double-blind, placebo-controlled trial, 46 inpatients with BD undergoing ECT were allocated 1:1 to receive either melatonin (3 mg nightly) or identical placebo capsules. Study medication was administered from 24 h before the first ECT session until 24 h after the final session. Cognitive outcomes were assessed using the Mini-Mental State Examination (MMSE) and its subdomains at baseline and after each ECT session. Secondary outcomes included systolic and diastolic blood pressure. Adverse events were recorded throughout the trial.
Results: Compared with placebo, melatonin significantly improved global cognition across the ECT course (group × time interaction, p=0.021). At the final session, patients receiving melatonin demonstrated higher MMSE scores (27.9 ± 1.8 vs. 26.5 ± 2.0), with the strongest improvements in recall (+0.6 points, p=0.012) and attention/calculation (+0.5 points, p=0.018). Blood pressure (BP) values remained stable (ΔSBP: –1.2 ± 3.1 mmHg melatonin vs. –0.8 ± 2.9 mmHg placebo, p=0.64), and melatonin was also well tolerated.
Conclusion: Adjunctive melatonin reduced ECT-related cognitive impairment in BD patients, with pronounced benefits in memory and attention, while maintaining an excellent safety profile. These findings support melatonin as a simple, inexpensive, and widely accessible therapeutic option to support cognition in this vulnerable population.
Keywords: Bipolar disorder, Electroconvulsive therapy, Cognitive impairment, Melatonin, Adjunctive Therapy
Type of Study: Original |
Subject:
Clinical Neuroscience
Received: 2025/08/26 | Accepted: 2025/11/10
Received: 2025/08/26 | Accepted: 2025/11/10
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