Exploring the feasibility, safety and preliminary clinical effects of amygdala-targeted temporal interference stimulation for major depressive disorder: a pilot study

Temporal interference stimulation (TIS) is a novel noninvasive neuromodulation technique. However, whether it can be applied in patients with major depressive disorder (MDD) remains unclear. This pilot study investigated the feasibility, safety, and preliminary clinical effects of amygdala-targeted TIS in patients with MDD. In this single-center, single-arm pilot study, 32 MDD patients received a 5-day amygdala-targeted TIS. The primary outcomes were feasibility (defined by the intervention completion rate) and safety (evaluated through participant-reported adverse events). The secondary outcomes assessed preliminary clinical efficacy, including changes in depressive symptoms measured by the 17-item Hamilton Depression Rating Scale (HAMD-17) and Montgomery-Åsberg Depression Rating Scale (MADRS), as well as anxiety, anhedonia, sleep quality, and health-related quality of life. Assessments were performed at baseline, postintervention, and at the 1-week and 1-month follow-ups. Statistical analyses included mainly linear mixed-effects models and paired t tests. All participants completed the full intervention while maintaining stable psychiatric medication. TIS was well tolerated, with mostly mild adverse events (sleepiness, 24.1%; dizziness, 14.1%; unusual scalp sensations, 10.5%) and no serious safety concerns. The HAMD-17 response rates were 59.4% post-intervention, 65.4% at the 1-week follow-up, and 50.0% at the 1-month follow-up. The corresponding MADRS response rates were 54.8%, 65.4%, and 53.3%, respectively. Significant improvements were also observed in anxiety, anhedonia, sleep quality, and quality of life. This pilot study suggests that amygdala-targeted TIS is feasible, well tolerated, and associated with promising clinical improvements in patients with MDD, warranting further investigation in randomized controlled trials. This study has been prospectively registered at ClinicalTrials.gov on June 14, 2024 (Registration ID: NCT06461260).