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Brain Stimul. 2014 Nov-Dec;7(6):855-63. doi: 10.1016/j.brs.2014.07.040. Epub 2014 Aug 7.

The efficacy and safety of low frequency repetitive transcranial magnetic stimulation for treatment-resistant depression: the results from a large multicenter French RCT.

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Université de Lyon, Université Claude Bernard Lyon I, EA 4615, Centre Hospitalier le Vinatier, Bron F-69003, France. Electronic address:
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.
CHU Dijon, Hôpital Général, Service de Psychiatrie et d'Addictologie, 21000 Dijon, France.
CHU Hôpital La Colombière, 34000 Montpellier, France.
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.
CHU St Etienne, Hôpital Nord, 42055 St Etienne Cedex, France.
EPS de Ville Evrard, Unité de Saint-Denis, 93200 Saint-Denis, France.
CHU Besançon, Department of Clinical Psychiatry, University Hospital, 25000 Besançon, France.
Pôle "Information Médicale Evaluation Recherche" (IMER) 62 Avenue Lacassagne Bât A, 69424 Lyon cedex 03 CHU Lyon, France.
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.



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).


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.


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).


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.



1 Hz; Depression; Dorsolateral prefrontal cortex; Low frequency; Venlafaxine; rTMS

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