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

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


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.

Trial registration: NCT00714090.

Keywords: 1 Hz; Depression; Dorsolateral prefrontal cortex; Low frequency; Venlafaxine; rTMS.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use
  • Combined Modality Therapy
  • Cyclohexanols / adverse effects
  • Cyclohexanols / therapeutic use
  • Depressive Disorder, Treatment-Resistant / drug therapy
  • Depressive Disorder, Treatment-Resistant / therapy*
  • Double-Blind Method
  • Female
  • France
  • Humans
  • Male
  • Middle Aged
  • Prefrontal Cortex / physiology*
  • Time Factors
  • Transcranial Magnetic Stimulation / adverse effects*
  • Venlafaxine Hydrochloride


  • Antidepressive Agents
  • Cyclohexanols
  • Venlafaxine Hydrochloride

Associated data