Treatment of Bipolar Depression With H1-Coil Deep Brain rTMS: Clinical-Cognitive and Safety Evaluation

The present research protocol will evaluate clinical-cognitive and safety effects of H1-Coil Deep Brain Transcranial Magnetic Stimulation over prefrontal cortex in subjects with bipolar depression, currently treated with mood stabilizer and/or antipsychotics for stabilization and sleep regulation. Patients will be clinically evaluated with the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) criteria for Bipolar Depressive Episode. Symptoms intensity will be rated according to The Hamilton Depression Scale (HAMD -17 items) - main outcome. Patients with scores higher than 18 will be included and the cognitives functions will be evaluated according with tasks of neuropsychologic battery chosen. Patients with active neurological or severe disorders (such as cancer, auto-imune and cardiologic disorders) will be excluded. The present study is a double-blinded, controlled, randomized trial with 50 patients in bipolar depression episode. The intervention protocol consist in 20 consecutive daily deep TMS sessions (skipping the weekend). After meeting eligibility criteria, patients will be randomized (computer generated list) to one of the two intervention groups: 25 patients in Active H1-Coil deep brain rTMS group and Sham H1-Coil deep brain rTMS group. H1-Coil deep brain rTMS sessions will follow the following steps: the first day of treatment, patients will be instructed to wear earplugs to minimize the risk of impaired hearing. Then, the threshold intensity of stimulation motor is determined by applying pulses only to the motor cortex. The stimulation threshold is determined pro gradually increase the stimulation intensity every 5 seconds. The stimulation threshold is defined as stimulation of lesser intensity that can evoked motor potential with at least 50μV amplitude of at least 5 tentativas.A coil is positioned to 5 centimeters below the hot spot (in the prefrontal area) intensity - 120% of the threshold engine. Each session will receive 55 groups of stimuli, duration - 2/2 , frequency - 18 Hz , area - left prefrontal , intervals - 20 seconds . Soon, 1,980 pulses of magnetic stimulation will be administered every day (per session), totaling 39,600 pulses throughout treatment. Patients will be clinically assessed at baseline, weekly during the four weeks of treatment and for four weeks after completion of treatment ending in 8 weeks. Main outcome will be based on HAMD-17 items at a endpoint of 4-weeks and follow up 4-weeks, with secondary outcomes assessing Young Mania Rating Scale (11 items) at 8 weeks. Other evaluation scales include, Hamilton Anxiety Scale, Global Assessment Scale and Clinical Global Impression at 8 weeks. The cognitive assessment will be performed with a neuropsychologic battery tests at baseline, endpoint of 4-weeks and endpoint of 8-weeks with a trained neuropsychologist. Also a Safety Deep rTMS Scale, adverse effects scales and clinical evaluation with a trained physician.