Real-world effectiveness of a single-day course of transcranial magnetic stimulation using an Optimized, Neuroplasticity-Enhanced regimen in Bipolar Depression (ONE-BD)

Recently, novel regimens for transcranial magnetic stimulation (TMS) have been reported, combining multiple sessions per day with pharmacological augmentation of neuroplasticity, to enable delivery of an entire treatment course in a single day. Here we report outcomes for a single-day, optimized neuroplasticity-enhanced regimen in bipolar depression (ONE-BD). 30 TMS-eligible adults with bipolar disorder, type I, and a current depressive episode underwent 20 sessions of TMS (q 20min, iTBS, 600 pulses, dorsomedial prefrontal target Fz) with 125mg D-cycloserine given 1h pre-treatment. All patients completed treatment, with no serious adverse events or switch to mania/hypomania. Response trajectories showed progressive improvement over 6 weeks post-treatment. On HDRS-17, scores improved from 24.0±SD4.3 (baseline) to 9.1±SD6.4 at week 6 and 9.9±SD5.2 at week 12. On BDI-II, scores improved from 35.2±SD10.6 (baseline) to 13.2±SD11.9 at week 6 and 12.7±SD11.2 at week 12. On PHQ9, scores improved from 17.0±SD5.5 (baseline) to 6.3±SD6.2 at week 6 and 7.3±SD5.8 at week 12. On GAD-7, scores improved from 13.2±SD4.7 (baseline) to 5.9±SD5.6 at week 6 and 5.4±SD5.9 at week 12. Response/remission rates at week 6 were 73.3% and 43.3% (HDRS-17), 70.0% and 46.7% (BDI-II), 73.3% and 46.7% (PHQ-9), and 76.7% and 50.0% (GAD-7). YMRS scores remained low and stable from 6.0±SD5.5 at baseline to 3.9±SD5.0 at week 6. This preliminary report suggests that single-day TMS regimens appear safe and well-tolerated, with clinically meaningful response and remission rates. Randomized controlled studies would allow further validation of the approach, and optimization of augmentation regimen, stimulation target, and inter-session interval.