Real-world effectiveness of a single-day regimen for transcranial magnetic stimulation using Optimized, Neuroplastogen-Enhanced techniques in Depression (ONE-D)

Background: Conventional transcranial magnetic stimulation (TMS) regimens are logistically burdensome, requiring days or weeks of clinic visits. Here we describe a TMS regimen enabling delivery of an entire therapeutic course in a single day. Methods: This retrospective case series reports outcomes for an optimized, neuroplastogen-enhanced depression (ONE-D) treatment regimen delivering 600-pulse iTBS (120% MT) targeting left DLPFC via scalp heuristic, every 30 minutes for 20 sessions in 9.5 hours, enhancing neuroplasticity via single-dose d-cycloserine (125 mg) and lisdexamfetamine (20 mg), off-label, given 1 hour pre-treatment. 32 TMS-eligible adults with medication-resistant unipolar depression underwent the ONE-D regimen, with assessments on day-of-treatment then weekly x 6 weeks (HDRS-17, BDI-II, PHQ-9, and GAD-7). Results: Every patient completed the regimen successfully, with no serious adverse events (mean scalp discomfort, 5.8±2.1/10). Response was not immediate but followed an exponential-decay trajectory over the 6-week followup: mean weekly scores of 22.6±5.3(baseline), 13.5±6.4, 10.6±6.4, 7.9±4.9, 6.6±4.9, 6.3±4.8, 5.5±4.2 (HDRS-17), 37.5±9.0(baseline), 23.8±12.2, 17.1±11.1, 14.1±11.2, 11.0±8.7, 9.5±8.2, 7.6±7.8 (BDI-II,) 18.4±3.5(baseline), 11.4±5.1, 9.4±5.7, 6.9±5.2, 6.0±3.9, 5.3±4.0, 4.6±4.2 (PHQ-9), 14.3±5.2(baseline), 8.7±4.5, 6.4±5.0, 4.3±4.0, 3.8±3.6, 3.3±3.3, 3.1±2.7 (GAD-7). Response / remission rates (cross-sectional, not aggregated) were 90.3% and 74.2% (HDRS-17), 93.5% and 71.0% (BDI-II), 90.3% and 58.1% (PHQ-9), 93.3% and 76.7% (GAD-7) at week 6, and 92.6% and 77.8% (HDRS-17), 92.3% and 73.1% (BDI-II), 86.4% and 65.4% (PHQ-9), 91.7% and 80.0% (GAD-7) at week 12. Conclusion: Delivery of an effective TMS course in one day appears feasible, safe, and well-tolerated. With neuroplastogen-enhancement, despite non-personalized, scalp-based targeting, the response and remission rates appeared robust and sustained in representative clinical populations. Follow-up studies may allow further acceleration of the regimen and generalization to other TMS indications.