title: Treatment of Bipolar Depression with Deep TMS: Results from a Double-Blind, Randomized, Parallel Group, Sham-Controlled Clinical Trial.
abstract: Bipolar depression (BD) is a highly prevalent condition with limited therapeutic options. Deep (H1-coil) transcranial magnetic stimulation (dTMS) is a novel TMS modality with established efficacy for unipolar depression. We conducted a randomized sham-controlled trial to evaluate the efficacy and safety of dTMS in treatment-resistant BD patients. Patients received 20 sessions of active or sham dTMS over the left dorsolateral prefrontal cortex (H1-coil, 55 18 Hz 2 s 120% MT trains). The primary outcome was changes in the 17-item Hamilton Depression Rating Scale (HDRS-17) from baseline to endpoint (week 4). Secondary outcomes were changes from baseline to the end of the follow-up phase (week 8), and response and remission rates. Safety was assessed using a dTMS adverse effects questionnaire and the Young Mania Rating Scale to assess treatment-emergent mania switch (TEMS). Out of 50 patients, 43 finished the trial. There were 2 and 5 dropouts in the sham and active groups, respectively. Active dTMS was superior to sham at end point (difference favoring dTMS=4.88; 95% CI 0.43 to 9.32, p=0.03) but not at follow-up. There was also a trend for greater response rates in the active (48%) vs sham (24%) groups (OR=2.92; 95% CI=0.87 to 9.78, p=0.08). Remission rates were not statistically different. No TEMS episodes were observed. Deep TMS is a potentially effective and well-tolerated add-on therapy in resistant bipolar depressed patients receiving adequate pharmacotherapy.
authors.affiliation: Service of Interdisciplinary Neuromodulation (SIN-EMT), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.|Mood Disorders Unit (GRUDA), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Diego F
authors.initials: DF
authors.lastname: Tavares
authors.affiliation: Service of Interdisciplinary Neuromodulation (SIN-EMT), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Myczkowski
authors.affiliation: Service of Interdisciplinary Neuromodulation (SIN-EMT), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Rodrigo L
authors.initials: RL
authors.lastname: Alberto
authors.affiliation: Service of Interdisciplinary Neuromodulation (SIN-EMT), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.|Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: Valiengo
authors.affiliation: Service of Interdisciplinary Neuromodulation (SIN-EMT), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Rios
authors.affiliation: Service of Interdisciplinary Neuromodulation (SIN-EMT), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Pedro
authors.initials: P
authors.lastname: Gordon
authors.affiliation: Service of Interdisciplinary Neuromodulation (SIN-EMT), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.|University Hospital, University of São Paulo, São Paulo, Brazil.
authors.forename: Bernardo
authors.initials: B
authors.lastname: de Sampaio-Junior
authors.affiliation: Service of Interdisciplinary Neuromodulation (SIN-EMT), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.|University Hospital, University of São Paulo, São Paulo, Brazil.
authors.forename: Izio
authors.initials: I
authors.lastname: Klein
authors.affiliation: Service of Interdisciplinary Neuromodulation (SIN-EMT), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Mansur
authors.affiliation: Department and Institute of Neurology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Marcolin
authors.affiliation: Service of Interdisciplinary Neuromodulation (SIN-EMT), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Beny
authors.initials: B
authors.lastname: Lafer
authors.affiliation: Mood Disorders Unit (GRUDA), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Moreno
authors.affiliation: Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil.
authors.forename: Wagner
authors.initials: W
authors.lastname: Gattaz
authors.affiliation: Centre for Addiction and Mental Health, Clarke Division, Toronto, Ontario, Canada.
authors.forename: Zafiris J
authors.initials: ZJ
authors.lastname: Daskalakis
authors.affiliation: Service of Interdisciplinary Neuromodulation (SIN-EMT), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.|Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil.|University Hospital, University of São Paulo, São Paulo, Brazil.
authors.forename: André R
authors.initials: AR
authors.lastname: Brunoni
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010352:Patient Dropouts; D017397:Prefrontal Cortex; D011569:Psychiatric Status Rating Scales; D012074:Remission Induction; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents