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

- 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.

ContextThe 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).MethodIn 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.ResultsWe 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).ConclusionLow 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.