Transcranial temporal interference stimulation for treating bipolar disorder with depressive episodes: a feasibility Study.

Bipolar depression (BD-D) is a significant clinical challenge associated with high disease burden. Transcranial temporal interference stimulation (tTIS), a novel and noninvasive approach for targeting deep brain structures, was investigated for its efficacy and safety in BD-D patients in this trial. Thirty-six patients were recruited for a single-arm, open-label trial, and 25 completed the 5-day intervention consisting of 10 tTIS sessions targeting the left nucleus accumbens. Each session lasted 20 min, with a maximum current intensity of 2 mA and an envelope stimulation frequency of 40 Hz. Significant symptom reductions were observed following treatment, with mean HAMD-17 scores decreasing from 23.36 to 16.16 (p < 0.0001), MADRS scores from 39.12 to 31.28 (p < 0.01), HAMA scores from 19.68 to 15.44 (p < 0.05), and QIDS scores from 13.52to 9.68 (p < 0.001). Eleven participants (44.0%) met improvement criteria and seven (28.0%) achieved response. Cognitive assessments indicated improvements in memory and executive function, and changes in reward-related brain activity correlated positively with symptom reduction. Adverse events were mild, mainly transient scalp discomfort. These findings provide preliminary evidence supporting the efficacy and safety of tTIS for alleviating depressive symptoms and cognitive impairments in BD-D.