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The Efficacy and Safety of Low Frequency Repetitive Transcranial Magnetic Stimulation for Treatment-resistant Depression: The Results From a Large Multicenter French RCT

  • Jerome Brunelin
    Correspondence
    Corresponding author. CH Le Vinatier - EA4615, 95 boulevard Pinel, BP 300 39; 69 678 Bron cedex, France. Tel.: +33 (0)4 37 91 55 65.
    Affiliations
    Université de Lyon, Université Claude Bernard Lyon I, EA 4615, Centre Hospitalier le Vinatier, Bron F-69003, France
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  • Isabelle Jalenques
    Affiliations
    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
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  • Benoit Trojak
    Affiliations
    CHU Dijon, Hôpital Général, Service de Psychiatrie et d'Addictologie, 21000 Dijon, France
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  • Jerome Attal
    Affiliations
    CHU Hôpital La Colombière, 34000 Montpellier, France
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  • David Szekely
    Affiliations
    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
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  • Aurélia Gay
    Affiliations
    CHU St Etienne, Hôpital Nord, 42055 St Etienne Cedex, France
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  • Dominique Januel
    Affiliations
    EPS de Ville Evrard, Unité de Saint-Denis, 93200 Saint-Denis, France
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  • Emmanuel Haffen
    Affiliations
    CHU Besançon, Department of Clinical Psychiatry, University Hospital, 25000 Besançon, France
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  • Anne-Marie Schott-Pethelaz
    Affiliations
    Pôle “Information Médicale Evaluation Recherche” (IMER) 62 Avenue Lacassagne Bât A, 69424 Lyon cedex 03 CHU Lyon, France
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  • Coralie Brault
    Affiliations
    Pôle “Information Médicale Evaluation Recherche” (IMER) 62 Avenue Lacassagne Bât A, 69424 Lyon cedex 03 CHU Lyon, France
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  • The STEP Group
    Author Footnotes
    1 The STEP Group: Abderrafi AÏT-AMEUR, René BENADHIRA, Michel BENOIT, Maxime BUBROVSZKY, Yannick CELLIER, Irena CUSSAC, Caroline DUBERTRET, Frédéric HAESEBAERT, Jerome HOLTZMANN, Némat JAAFARI, Catherine MASSOUBRE, Vincent MEILLE, Cecilia NAUCZYCIEL, Marion PLAZE, Fady RACHID, Raphaëlle RICHIERI.
  • Emmanuel Poulet
    Affiliations
    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
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  • Author Footnotes
    1 The STEP Group: Abderrafi AÏT-AMEUR, René BENADHIRA, Michel BENOIT, Maxime BUBROVSZKY, Yannick CELLIER, Irena CUSSAC, Caroline DUBERTRET, Frédéric HAESEBAERT, Jerome HOLTZMANN, Némat JAAFARI, Catherine MASSOUBRE, Vincent MEILLE, Cecilia NAUCZYCIEL, Marion PLAZE, Fady RACHID, Raphaëlle RICHIERI.
Published:August 06, 2014DOI:https://doi.org/10.1016/j.brs.2014.07.040

      Highlights

      • Large, multisite, randomized controlled trial (170 patients with resistant MDD)
      • rTMS is as effective as venlafaxine and as the combination of venlafaxine and rTMS
      • 1 Hz rTMS over the right PFC might be a useful alternative treatment of TRD.

      Abstract

      Context

      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).

      Method

      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).

      Conclusion

      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.

      Keywords

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