Dorsomedial prefrontal cortex repetitive transcranial magnetic stimulation for treatment-refractory major depressive disorder: A three-arm, blinded, randomized controlled trial. 
Dorsomedial prefrontal cortex (DMPFC) repetitive transcranial magnetic stimulation (rTMS) is a novel intervention for treatment-refractory depression (TRD).  To date, many open-label case series and one randomized controlled trial of modest sample size have provided preliminary evidence that DMPFC-rTMS is an effective treatment for TRD.  Here, we report the results of a large, double-blinded, sham-controlled trial of DMPFC-rTMS for TRD.  The primary aim of this study was to determine the efficacy of DMPFC-rTMS for TRD under sham-controlled conditions.  120 TRD patients were randomized to receive 30 twice-daily sessions of either active high-frequency, active low-frequency, or sham DMPFC-rTMS using a novel bent active/sham double-cone coil.  Placebo stimulation also involved the use of surface electrodes placed above the eyebrows.  The 17-item Hamilton Rating Scale for Depression served as the primary outcome measure.  Although there was a significant main effect of treatment across all arms, active DMPFC-rTMS was not superior to sham.  Both participants and assessors were unable to accuracy determine whether patients received active or placebo stimulation.  However, technicians' treatment arm guesses were significantly above chance.  DMPFC rTMS did not result in improvement of depressive symptoms greater than sham stimulation.  We cannot rule out that the sham apparatus may also have elicited an antidepressant effect via electrical trigeminal stimulation; future DMPFC-rTMS trials are therefore warranted.