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Updated: Apr 24, 2026

Robotically Delivered fMRI-Guided Personalized Transcranial Magnetic Stimulation Therapy for Treatment-Resistant Depression
Published on: April 10, 2026
Cost-Effectiveness of Transcranial Magnetic Stimulation and Virtual Reality-Based Cognitive Remediation for
Federica Sancassiani1,2, Martino Belvederi Murri3,4, Clelia Madeddu1,5
1Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Introduction:
This paper presents a research protocol of a randomized controlled trial aimed to evaluate the feasibility and the cost-effectiveness of non-pharmacological interventions for depressive symptoms, quality of life, depression-related conditions, and cognitive function among patients with cancer. Specifically, repetitive transcranial magnetic stimulation (rTMS) and virtual reality-based cognitive remediation (VR-COG) will be analyzed, alongside standard treatment as usual (TAU), in comparison to TAU alone.
Methods:
100 participants will be enrolled: 60 from the Health Trust of Ferrara randomized 1:1:1 to (a) TAU, (b) rTMS + TAU, and (c) VR-COG + TAU, and 40 from the University Hospital of Cagliari randomized 1:1 to (a) TAU and (b) VR-COG + TAU. The inclusion criteria will be as follows: patients aged 18 years and older, both sexes, a diagnosis of oncological disease within the last 5 years in a non-advanced stage, a diagnosis of major depressive disorder according to DSM-5 criteria, and a score of≥14 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17). The VR-COG program will include a series of exercises in virtual sailing scenarios using the software CEREBRUM. The rTMS program will be delivered at 50% of the resting motor threshold. Personalized targets created for each individual will be located at various cortical depths. TAU will include psychiatric visits and psychological counseling. All the interventions will last 3 months, with pre-post evaluation for outcomes of interest and 3-6 months of follow-up.
Results:
The results of the trial will be published in international peer-reviewed journals and will be disseminated at international meetings and congresses.
Discussion:
The results of this study will be useful for obtaining knowledge for clinical practice regarding the feasibility and cost-effectiveness of innovative therapeutic approaches aimed at treating depression in individuals suffering from oncological pathologies.
Conclusion:
The monitoring of the program's cost-effectiveness, encompassing both the screening and intervention phases, will enable policymakers to inform the implementation of this evidence in routine clinical practice.
Clinical Trial Registration Number:
The study has been registered on the ClinicalTrials.gov website with ID no. NCT06589544.

