Katharine Dunlop1, Jack Sheen2, Laura Schulze2, Peter Fettes2, Farrokh Mansouri3, Kfir Feffer4, Daniel M Blumberger5, Zafiris J Daskalakis5, Sidney H Kennedy6, Peter Giacobbe7, Blake Woodside8, Jonathan Downar9. 1. Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States. Electronic address: kad2032@med.cornell.edu. 2. Institute of Medical Science, University of Toronto, Toronto, Canada. 3. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada. 4. Lev-Hasharon Mental Health Center, Tzur-Moshe, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 5. Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada. 6. Institute of Medical Science, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada; Krembil Research Institute, University Health Network, Toronto, Canada. 7. Institute of Medical Science, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Department of Psychiatry, University Health Network, Toronto, Canada; Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, Canada. 8. Department of Psychiatry, University of Toronto, Toronto, Canada; Department of Psychiatry, University Health Network, Toronto, Canada. 9. Institute of Medical Science, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Department of Psychiatry, University Health Network, Toronto, Canada; Krembil Research Institute, University Health Network, Toronto, Canada.
Abstract
BACKGROUND: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. OBJECTIVE: The primary aim of this study was to determine the efficacy of DMPFC-rTMS for TRD under sham-controlled conditions. METHODS: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. RESULTS: 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. CONCLUSION: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.
RCT Entities:
BACKGROUND: 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. OBJECTIVE: The primary aim of this study was to determine the efficacy of DMPFC-rTMS for TRD under sham-controlled conditions. METHODS: 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. RESULTS: 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. CONCLUSION: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.