title: Augmentative repetitive Transcranial Magnetic Stimulation (rTMS) in the acute treatment of poor responder depressed patients: a comparison study between high and low frequency stimulation.
abstract: BACKGROUND
  While the efficacy of repetitive transcranial magnetic stimulation (rTMS) in Major Depressive Disorder (MDD) is well established, the debate is still open in relation to bipolar depression and to a possible different effectiveness of high vs. low stimulation. The present study was aimed to assess and compare the efficacy and tolerability of different protocols of augmentative rTMS in a sample of patients with current Major Depressive Episode (MDE), poor drug response/treatment resistance and a diagnosis of MDD or bipolar disorder.
  
  
  METHODS
  Thirty-three patients were recruited in a 4-week, blind-rater, rTMS trial and randomised to the following three groups of stimulation: (1) (n=10) right dorsolateral prefrontal cortex (DLPFC) 1 HZ, 110% of the motor threshold (MT), 420 stimuli/day; (2) (n=10) right DLPFC, 1Hz, 110% MT, 900 stimuli/day; (3) (n=13) left DLPFC, 10Hz, 80% MT, 750 stimuli/day.
  
  
  RESULTS
  Twenty-nine patients completed the treatment, showing a significant reduction of primary outcome measures (HAM-D, MADRS and CGI-S total scores: t=8.1, P<0.001; t=8.6, P<0.001; t=4.6, P<0.001 respectively). No significant differences in terms of efficacy and tolerability were found between high vs. low frequency and between unipolar and bipolar patients. Side effects were reported by 21% of the sample. One of the 4 dropouts was caused by a hypomanic switch.
  
  
  CONCLUSIONS
  Augmentative rTMS appeared to be effective and well tolerated for the acute treatment of unipolar and bipolar depression with features of poor drug response/treatment resistance, showing a comparable effectiveness profile between protocols of high and low frequency stimulation.
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milano, Italy; Bipolar Disorders Clinic, Stanford Medical School, Stanford University, CA, USA. Electronic address: bernardo.dellosso@unimi.it.
authors.forename: B
authors.initials: B
authors.lastname: Dell'Osso
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Oldani
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milano, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Camuri
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Dobrea
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cremaschi
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milano, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Benatti
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Arici
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milano, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Grancini
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milano, Italy.
authors.forename: A Carlo
authors.initials: AC
authors.lastname: Altamura
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000523:psychology / Q000628:therapy*; D003865:Major Depressive Disorder / Q000523:psychology / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex; D016037:Single-Blind Method; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome
keywords: Augmentation; Bipolar disorder; Major depressive disorder; Poor drug response; Repetitive transcranial magnetic stimulation (rTMS); Treatment resistance