- OBJECTIVE: To perform a randomized, sham-controlled phase I/IIa trial to study safety and efficacy of deep rTMS on fatigue and depression in patients with MS (NCT01106365). BACKGROUND: Fatigue and depression are frequent symptoms among multiple sclerosis (MS) patients. The underlying pathobiology is poorly understood and therapeutic strategies are limited. Repetitive transcranial magnetic stimulation (rTMS) has shown efficacy in the treatment of major depression. The recently developed H-Coil, allows stimulation of deeper brain regions, possibly involved in the pathophysiology of fatigue and depression. H-coil stimulation is safe and well tolerated in healthy volunteers, and has shown efficacy in patients with major depression. DESIGN/METHODS: 28 MS patients (42.9 ± 9.2 years) underwent 18 sessions of deep rTMS over 6 weeks. Nine patients received true stimulation (18Hz, 120% resting motor threshold) of the left prefrontal cortex (PFC), 10 patients bilateral motor cortex (MC) stimulation (5Hz, 90% resting motor threshold) and 10 patients received sham stimulation over the left PFC. Fatigue was assessed by the Fatigue Severity Scale (FSS), the Modified Fatigue Impact Scale (MFIS), the Epworth Sleepiness Scale (ESS) and a Visual Analogue Scale (VAS). Depression was rated with the 18-item Hamilton Rating Scale for Depression (HAMDS) and the Beck’s Depression Inventory (BDI). RESULTS: No changes in FSS and BDI were observed under sham- and true PFC stimulation. In contrast, the MC group showed a numerical, non-significant decrease in the FSS during treatment reaching significance in the follow up phase (-26.72% ± 16.3%, p=0.001). MC stimulation also lead to a significant decrease in BDI values two weeks after first stimulation (-25.74%±24.36%, p=0.013), reaching a maximum during follow up (-39.23%±21.57, p=0.001). Results of the other rating scales were in line with FSS- and BDI results. CONCLUSIONS: Our data suggest that deep rTMS of the motor cortex has the potential to ameliorate MS-related fatigue and depression outlasting the time of stimulation. Disclosure: Dr. Schippling has received personal compensation for activities with Novartis, and Bayer Schering. Dr. Schippling has received research support from Bayer Schering and Biogen Idec. Dr. Tiede has nothing to disclose. Dr. Lorenz has nothing to disclose. Dr. Pfueller has nothing to disclose. Dr. Dorr has nothing to disclose. Dr. Bellmann-Strobl has nothing to disclose. Dr. Zangen has received royalty payments from the National Institutes of Health and the Weizmann Institute. Dr. Zangen holds stock and/or stock options from Brainsway. Dr. Zangen has received research support from Brainsway and Teva Neuroscience. Dr. Paul has received personal compensation for activities with Teva Neuroscience, Sanofi-Aventis Pharmaceuticals Inc., Merck Serono, Biogen Idec, Bayer Pharmaceuticals Corp., Novartis, and the Guthy Jackson Charitable Foundation. Dr. Paul has received research support from Bayer Schering, Merck Serono, Teva Neuroscience and Novartis. Dr. Gaede has nothing to disclose.