title: The efficacy and safety of low frequency repetitive transcranial magnetic stimulation for treatment-resistant depression: the results from a large multicenter French RCT.
abstract: BACKGROUND
  The aim of this study was to assess whether the combination of low frequency repetitive transcranial magnetic stimulation (rTMS) and venlafaxine (150-225 mg/day) is effective and safe for treatment-resistant unipolar depression (TRD).
  
  
  METHODS
  In a multicenter (18 centers) randomized double blind controlled trial with three arms, 170 patients were allocated to receive active rTMS combined with active venlafaxine (n = 55), active rTMS combined with placebo venlafaxine (n = 60) or sham rTMS combined with active venlafaxine (n = 55). The patients received once daily sessions of active or sham 1 Hz rTMS applied over the right dorsolateral prefrontal cortex (360 pulses/day delivered at 120% of the resting motor threshold) for two to six weeks; rTMS was combined with active or sham venlafaxine (mean dose: 179.0 ± 36.6 mg/day). The primary outcome was the number of patients who achieved remission, which was defined as an HDRS17 score <8.
  
  
  RESULTS
  We reported a similar significant antidepressant effect in the 3 groups (P < 10(-6)), with a comparable delay of action and a comparable number of remitters at the endpoint (28% in the combination group, 41% in the rTMS group and 43% in the venlafaxine group; P = 0.59).
  
  
  CONCLUSIONS
  Low frequency rTMS appears to be as effective as venlafaxine and as effective as the combination of both treatments for TRD. Because of its short session duration (the duration of one session was 8.5 min) and its safety, slow rTMS might be a useful alternative treatment for patients with TRD.
authors.affiliation: Université de Lyon, Université Claude Bernard Lyon I, EA 4615, Centre Hospitalier le Vinatier, Bron F-69003, France. Electronic address: jerome.brunelin@ch-le-vinatier.fr.
authors.forename: Jerome
authors.initials: J
authors.lastname: Brunelin
authors.affiliation: CHU Clermont-Ferrand, Service de Psychiatrie de l'Adulte A et Psychologie médicale, F-63003 Clermont-Ferrand, France; Clermont Université, Université d'Auvergne Clermont 1, UFR Médecine, Equipe d'Accueil 7280, F-63001 Clermont-Ferrand, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Jalenques
authors.affiliation: CHU Dijon, Hôpital Général, Service de Psychiatrie et d'Addictologie, 21000 Dijon, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Trojak
authors.affiliation: CHU Hôpital La Colombière, 34000 Montpellier, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Attal
authors.affiliation: Fonctions cérébrales et neuromodulation, Grenoble Institut des Neurosciences, Université Joseph Fourier, Grenoble, France; Clinique Universitaire de Psychiatrie, Pôle Psychiatrie-Neurologie, Centre Hospitalier Universitaire, Grenoble, France; UMS IRMaGe, Grenoble, France.
authors.forename: David
authors.initials: D
authors.lastname: Szekely
authors.affiliation: CHU St Etienne, Hôpital Nord, 42055 St Etienne Cedex, France.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Gay
authors.affiliation: EPS de Ville Evrard, Unité de Saint-Denis, 93200 Saint-Denis, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Januel
authors.affiliation: CHU Besançon, Department of Clinical Psychiatry, University Hospital, 25000 Besançon, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Haffen
authors.affiliation: Pôle "Information Médicale Evaluation Recherche" (IMER) 62 Avenue Lacassagne Bât A, 69424 Lyon cedex 03 CHU Lyon, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Schott-Pethelaz
authors.affiliation: Pôle "Information Médicale Evaluation Recherche" (IMER) 62 Avenue Lacassagne Bât A, 69424 Lyon cedex 03 CHU Lyon, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Brault
authors.affiliation: Université de Lyon, Université Claude Bernard Lyon I, EA 4615, Centre Hospitalier le Vinatier, Bron F-69003, France; CHU Lyon, Service de psychiatrie des urgences, Hôpital Edouard Herriot, Lyon, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Poulet
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003511:Cyclohexanols / Q000009:adverse effects / Q000627:therapeutic use; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000502:physiology*; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation / Q000009:adverse effects*; D000069470:Venlafaxine Hydrochloride
chemical_list: D000928:Antidepressive Agents; D003511:Cyclohexanols; D000069470:Venlafaxine Hydrochloride
keywords: 1 Hz; Depression; Dorsolateral prefrontal cortex; Low frequency; Venlafaxine; rTMS