Cost-Effectiveness of Transcranial Magnetic Stimulation and Virtual Reality-Based Cognitive Remediation for Depressive Symptoms among Cancer Patients: Protocol for a Three-Arm Randomized Controlled Trial

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.