Introduction
Stroke accounts for 2.5% of all deaths worldwide. It causes severe disabilities among survivors, making it the leading cause of disability. In the post-stroke period, the occurrence of depression and neuropsychological disorders is highly prevalent. Approximately 30% of stroke survivors experience depression and about 70% suffer from neuropsychological disorders, posing a significant burden on healthcare systems and patients. Neuropsychological disorders are usually characterized by specific deficits in learning, working memory, executive functions (such as inhibition and cognitive flexibility), attention, and processing speed.
Cognitive flexibility (the ability to shift between tasks), is one of the main dimensions of executive functioning that allows a person to control their actions and flexibly adapt to changing environments. Cognitive flexibility is mainly processed in the ventrolateral prefrontal cortex. Cognitive inhibition referees to the ability to stop a mental process, intentionally or unintentionally, for mental suppression of competing information. Cognitive inhibition activates the prefrontal cortex, left anterior insula, and dorsal frontal inhibitory system. In addition, parts of the dorsal anterior cingulate are involved during cognitive inhibition. Impairment of this cognitive function is a core feature of many major psychiatric disorders, including depression.
This study aims to compare the effectiveness of cognitive-behavioral therapy (CBT) combined with transcranial direct current stimulation (tDCS) versus CBT combined with pharmacotherapy in reducing depressive symptoms and improving executive functions (inhibition and cognitive flexibility) in stroke patients.

Method
This is a randomized controlled clinical trial with a pre-test/post-test/two-month follow-up design. The study population consists of all stroke patients referred to Dr. Hashemzahi's neurology clinic in Zahedan, south of Iran, in 2022. Initially, 138 individuals were assessed for eligibility. After applying the inclusion criteria, 57 individuals entered the study stages, and finally, data from 45 participants were analyzed. The eligible patients who were selected using a convenience sampling method and randomly assigned into three groups of 15. All participants completed three computerized tests at baseline including Stroop test, Go/No Go test, and Beck Depression Inventory (BDI). The first group received CBT plus tDCS (2 mA, five sessions per week for 4 weeks). The second group received CBT plus pharmacotherapy (10 mg citalopram for three weeks), and the third group received no intervention. At the end of the interventions and after two months, the computerized tests and BDI were administered again to all participants in three groups. The CBT was conducted at 12 sessions according to Kootker et al.'s CBT protocol for stroke patients. The data were analyzed by the mixed analysis of variance (ANOVA) in SPSS software, version 29.

Results
The results of mixed ANOVA indicated that the effects of time and group were significant on depression symptoms, but the interaction effect of time and group was not significant (Table 1). This means that depression scores were significantly different between at least two groups. Post hoc tests showed that two intervention groups were significantly different compared to the control group, but there was no significant difference between the two intervention groups. In other words, both CBT+tDCS and CBT+pharmacotherapy significantly reduced depression symptoms, and there was no significant difference between their effectiveness. Additionally, the comparison of three evaluation phases showed that depression level was significantly different between pre-test and post-test and between pre-test and follow-up phases, indicating the maintained effect of the interventions. However, changes in depression scores over three periods were not significantly different between the three groups.


 
Regarding cognitive flexibility and inhibition, the results indicated that the effect of time and group on both variables were significant, but the interaction effect of time and group was not significant. Post hoc tests indicated that only the CBT+tDCS was significantly different compared to the control group. Additionally, the differences in two variables were significant only between pre-test and post-test phases, and the effect was not maintained in the follow-up phase. Therefore, it can be said that the three groups had different trends over time.

Conclusions
The CBT combined with tDCS has a long-term effect on reducing depression symptoms and short-term effects on improving cognitive functions, including inhibition and cognitive flexibility in stroke patients. The CBT combined with pharmacotherapy (10 mg citalopram) has a long-term effect on alleviating depression symptoms but it has no significant effect on the cognitive functions.

Ethical Considerations

Compliance with ethical guidelines
A written informed consent was obtained from the participants and their information was kept confidential. They were free to leave the study at any time. This study was approved by Islamic Azad University, Torbat-e-Jam Branch (Code: IR.IAU.TJ.REC.1402.003) and was registered by the Iranian Registry of Clinical Trials (ID: IRCT20230618058511N1).

Funding
This study was from the PhD thesis of Elahe Moshtaghi, funded by Islamic Azad University, Torbat-e-Jam Branch. 

Authors contributions
Conceptualization and design: Elahe Moshtaghi and Mohammad Hossein Bayazi; data collection, data analysis, and initial draft preparation: Elahe Moshtaghi; supervision: Mohammad Hossein Bayazi; data analysis and interpretations: Behzad Rigi Koote. All authors read and approved the final version of the manuscript.

Conflicts of interest
According to the authors, there is no conflict of interest.

Acknowledgments
The authors would like to thank Dr. Hashemzahi and the staff of his neurology clinic, as well as all participants for their cooperation in this research.


 

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