Background: Videoconferencing-based treatments have shown great potential in increasing engagement and compliance by decreasing the barriers of time and distance. In general, employees tend to experience a lot of stress, but find it difficult to visit a clinic during office hours. Objective: The purpose of this study was to investigate the effectiveness of a mobile videoconference-based intervention for stress reduction and resilience enhancement in employees. Methods: In total, 81 participants were randomly allocated to one of the three conditions: mobile videoconferencing, in-person, and self-care; of these, 72 completed the study. All participants underwent assessment via self-reported questionnaires before, immediately after, and 1 month after the intervention. Intervention lasted for 4 weeks and consisted of elements of cognitive behavioral therapy, positive psychology, and meditation. Changes in clinical variables regarding stress and resilience across time were compared between treatment conditions. Results: There were significant condition × time effects on variables measuring perceived stress, resilience, emotional labor, and sleep, demonstrating significantly differential effects across time according to treatment condition. Moreover, there were significant effects of condition on perceived stress and occupational stress. There were no significant differences in any variable between the mobile videoconferencing and in-person conditions at 1 month after the intervention. Conclusions: Results indicate that both mobile videoconferencing and in-person interventions were comparably effective in decreasing stress and enhancing resilience. Further studies with a larger sample size and a longer follow-up period are warranted to investigate the long-term effect of mobile videoconferencing interventions. Trial Registration: ClinicalTrials.gov identifier NCT03256682; https://clinicaltrials.gov/study/NCT03256682 (Archived by WebCite at https://www.webcitation.org/71W77bwnR)
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