Open-label Study of Accelerated Low-Frequency TMS for Treatment-Resistant Depression in People With Epilepsy.

OBJECTIVE: This study aimed to evaluate the safety, feasibility, and preliminary clinical effects of an accelerated low-frequency transcranial magnetic stimulation (TMS) protocol in individuals with epilepsy and treatment-resistant depression (TRD). MATERIALS AND METHODS: In this prospective, open-label study, adults with epilepsy and TRD received accelerated 1-Hz TMS to the right dorsolateral prefrontal cortex. Primary end points were safety-assessed through seizure frequency, treatment-emergent adverse events, and cognitive performance-and feasibility, defined as completion of the protocol and tolerability. Secondary end points included changes in depressive symptoms, quality of life, and cognition. Participants were examined at baseline and at one- and six-month follow-up. RESULTS: A total of 12 participants completed the full protocol (100% retention). The intervention was well tolerated, and no increase in seizure frequency was observed at follow-up (baseline mean 2.1 seizures per month [SD 0.5]; one month, 1.8 [SD 0.6]; and six months, 2.2 [SD 0.6]). Depressive symptoms were significantly relieved (Quick Inventory of Depressive Symptomatology Self-Report: baseline mean 17.3 [SD 3.7]; one month, 8.8 [SD 4.6], p < 0.0001; six months, 9.9 [SD 4.1], p = 0.008). Quality-of-life scores did not significantly change overall, although selected subscales improved. No reduction in cognitive performance was detected across follow-up assessments. CONCLUSIONS: Accelerated low-frequency right prefrontal TMS appears safe, feasible, and associated with clinically meaningful improvements in depressive symptoms in individuals with epilepsy and TRD. These findings provide initial support for the use of TMS in a population often excluded from neuromodulation trials and highlight the need for controlled studies to determine efficacy and long-term outcomes. Registration for this clinical trial was submitted on March 6, 2017, and the first patient was enrolled on April 1, 2017. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03105700.