Efficacy and Safety of Transcranial Temporal Interference Stimulation for Treating Bipolar Disorder with Depressive Episodes

Background: Bipolar disorder (BD) presents significant challenges in clinical management, often characterized by persistent depressive symptoms and cognitive deficits. Transcranial temporal interference stimulation (tTIS) has shown promise in targeting deep brain structures with minimal invasiveness. This study aimed to assess the efficacy and safety of tTIS in newly diagnosed or medication-washout BD patients. Methods: We conducted a single-arm clinical trial with 36 BD patients who underwent 10 sessions of tTIS targeting the left nucleus accumbens over one week, with two sessions per day. Each tTIS session lasted 20 minutes, utilizing a maximum current intensity of 2 mA and an envelope stimulation frequency of 40 Hz. Depressive symptoms were assessed pre- and post-intervention using validated scales, including HAMD, QIDS, MADRS, and HAMA, while cognitive functions were evaluated using standardized neuropsychological tests. Safety was monitored through adverse event reporting. Results: Among 36 participants, 25 completed the full intervention protocol. Significant reductions were observed in depressive symptom scores: HAMD decreased from 23.36 to 16.16 (P < 0.0001), QIDS from 13.52 to 9.68 (P < 0.001), MADRS from 39.12 to 31.28 (P < 0.01), and HAMA from 19.68 to 15.44 (P < 0.05). Cognitive evaluations demonstrated notable improvements in memory and executive function. Adverse events were mild, primarily limited to transient scalp discomfort. Conclusions: This study provides preliminary evidence supporting the efficacy and safety of tTIS in alleviating depressive symptoms and improving cognitive function in BD patients.