Unilateral and bilateral MRI-targeted repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled study.
Several factors may mitigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) over sham rTMS in patients with treatment-resistant depression (TRD). These factors include unilateral stimulation (i.e., treatment of only the left dorsolateral prefrontal cortex [DLPFC]), suboptimal methods of targeting the DLPFC and insufficient stimulation intensity (based on coil-to-cortex distance).



We recruited patients with TRD between the ages of 18 and 85 years from a university hospital, and participants were randomized to receive sequential bilateral rTMS (600 pulses at 1 Hz followed by 1500 pulses at 10 Hz), unilateral high-frequency left (HFL)-rTMS (2100 pulses at 10 Hz) or sham rTMS for 3 or 6 weeks depending on treatment response. Stimulation was targeted with MRI localization over the junction of the middle and anterior thirds of the middle frontal gyrus, using 120% of the coil-to-cortex adjusted motor threshold. Our primary outcome of interest was the remission rate.



A total of 121 patients participated in this study. The remission rate was significantly higher in the bilateral group than the sham group. The remission rate in the HFL-rTMS group was intermediate and did not differ statistically from the rate in the 2 other groups. There were no significant differences in reduction of depression scores among the 3 groups.



The number of pulses used per session in the unilateral group was somewhat lower in our trial than in more recent trials, and the sham condition did not involve active stimulation.



Our findings suggest that sequential bilateral rTMS is superior to sham rTMS; however, adjusting for coil-to-cortex distance did not yield enhanced efficacy rates.
From the Temerty Centre for Therapeutic Brain Intervention, and Campbell Family Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Blumberger, Thomson, Mulsant, Rajji, Maher, Daskalakis); the Monash Alfred Psychiatry research centre, The Alfred and Monash University Central Clinical School, Melbourne, Australia (Maller, Fitzgerald); Cancer Care Ontario and the Dalla Lana School of Public Health, University of Toronto, Toronto, Ont., Canada (Brown); the Toronto Western Hospital, University Health Network, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Downar); and the Non-Invasive Neurostimulation Therapies laboratory, Department of Psychiatry, University of British Columbia, Vancouver, B.C., Canada (Vila-Rodriguez).
Daniel M
DM
Blumberger
From the Temerty Centre for Therapeutic Brain Intervention, and Campbell Family Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Blumberger, Thomson, Mulsant, Rajji, Maher, Daskalakis); the Monash Alfred Psychiatry research centre, The Alfred and Monash University Central Clinical School, Melbourne, Australia (Maller, Fitzgerald); Cancer Care Ontario and the Dalla Lana School of Public Health, University of Toronto, Toronto, Ont., Canada (Brown); the Toronto Western Hospital, University Health Network, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Downar); and the Non-Invasive Neurostimulation Therapies laboratory, Department of Psychiatry, University of British Columbia, Vancouver, B.C., Canada (Vila-Rodriguez).
Jerome J
JJ
Maller
From the Temerty Centre for Therapeutic Brain Intervention, and Campbell Family Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Blumberger, Thomson, Mulsant, Rajji, Maher, Daskalakis); the Monash Alfred Psychiatry research centre, The Alfred and Monash University Central Clinical School, Melbourne, Australia (Maller, Fitzgerald); Cancer Care Ontario and the Dalla Lana School of Public Health, University of Toronto, Toronto, Ont., Canada (Brown); the Toronto Western Hospital, University Health Network, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Downar); and the Non-Invasive Neurostimulation Therapies laboratory, Department of Psychiatry, University of British Columbia, Vancouver, B.C., Canada (Vila-Rodriguez).
Lauren
L
Thomson
From the Temerty Centre for Therapeutic Brain Intervention, and Campbell Family Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Blumberger, Thomson, Mulsant, Rajji, Maher, Daskalakis); the Monash Alfred Psychiatry research centre, The Alfred and Monash University Central Clinical School, Melbourne, Australia (Maller, Fitzgerald); Cancer Care Ontario and the Dalla Lana School of Public Health, University of Toronto, Toronto, Ont., Canada (Brown); the Toronto Western Hospital, University Health Network, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Downar); and the Non-Invasive Neurostimulation Therapies laboratory, Department of Psychiatry, University of British Columbia, Vancouver, B.C., Canada (Vila-Rodriguez).
Benoit H
BH
Mulsant
From the Temerty Centre for Therapeutic Brain Intervention, and Campbell Family Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Blumberger, Thomson, Mulsant, Rajji, Maher, Daskalakis); the Monash Alfred Psychiatry research centre, The Alfred and Monash University Central Clinical School, Melbourne, Australia (Maller, Fitzgerald); Cancer Care Ontario and the Dalla Lana School of Public Health, University of Toronto, Toronto, Ont., Canada (Brown); the Toronto Western Hospital, University Health Network, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Downar); and the Non-Invasive Neurostimulation Therapies laboratory, Department of Psychiatry, University of British Columbia, Vancouver, B.C., Canada (Vila-Rodriguez).
Tarek K
TK
Rajji
From the Temerty Centre for Therapeutic Brain Intervention, and Campbell Family Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Blumberger, Thomson, Mulsant, Rajji, Maher, Daskalakis); the Monash Alfred Psychiatry research centre, The Alfred and Monash University Central Clinical School, Melbourne, Australia (Maller, Fitzgerald); Cancer Care Ontario and the Dalla Lana School of Public Health, University of Toronto, Toronto, Ont., Canada (Brown); the Toronto Western Hospital, University Health Network, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Downar); and the Non-Invasive Neurostimulation Therapies laboratory, Department of Psychiatry, University of British Columbia, Vancouver, B.C., Canada (Vila-Rodriguez).
Missy
M
Maher
From the Temerty Centre for Therapeutic Brain Intervention, and Campbell Family Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Blumberger, Thomson, Mulsant, Rajji, Maher, Daskalakis); the Monash Alfred Psychiatry research centre, The Alfred and Monash University Central Clinical School, Melbourne, Australia (Maller, Fitzgerald); Cancer Care Ontario and the Dalla Lana School of Public Health, University of Toronto, Toronto, Ont., Canada (Brown); the Toronto Western Hospital, University Health Network, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Downar); and the Non-Invasive Neurostimulation Therapies laboratory, Department of Psychiatry, University of British Columbia, Vancouver, B.C., Canada (Vila-Rodriguez).
Patrick E
PE
Brown
From the Temerty Centre for Therapeutic Brain Intervention, and Campbell Family Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Blumberger, Thomson, Mulsant, Rajji, Maher, Daskalakis); the Monash Alfred Psychiatry research centre, The Alfred and Monash University Central Clinical School, Melbourne, Australia (Maller, Fitzgerald); Cancer Care Ontario and the Dalla Lana School of Public Health, University of Toronto, Toronto, Ont., Canada (Brown); the Toronto Western Hospital, University Health Network, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Downar); and the Non-Invasive Neurostimulation Therapies laboratory, Department of Psychiatry, University of British Columbia, Vancouver, B.C., Canada (Vila-Rodriguez).
Jonathan
J
Downar
From the Temerty Centre for Therapeutic Brain Intervention, and Campbell Family Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Blumberger, Thomson, Mulsant, Rajji, Maher, Daskalakis); the Monash Alfred Psychiatry research centre, The Alfred and Monash University Central Clinical School, Melbourne, Australia (Maller, Fitzgerald); Cancer Care Ontario and the Dalla Lana School of Public Health, University of Toronto, Toronto, Ont., Canada (Brown); the Toronto Western Hospital, University Health Network, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Downar); and the Non-Invasive Neurostimulation Therapies laboratory, Department of Psychiatry, University of British Columbia, Vancouver, B.C., Canada (Vila-Rodriguez).
Fidel
F
Vila-Rodriguez
From the Temerty Centre for Therapeutic Brain Intervention, and Campbell Family Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Blumberger, Thomson, Mulsant, Rajji, Maher, Daskalakis); the Monash Alfred Psychiatry research centre, The Alfred and Monash University Central Clinical School, Melbourne, Australia (Maller, Fitzgerald); Cancer Care Ontario and the Dalla Lana School of Public Health, University of Toronto, Toronto, Ont., Canada (Brown); the Toronto Western Hospital, University Health Network, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Downar); and the Non-Invasive Neurostimulation Therapies laboratory, Department of Psychiatry, University of British Columbia, Vancouver, B.C., Canada (Vila-Rodriguez).
Paul B
PB
Fitzgerald
From the Temerty Centre for Therapeutic Brain Intervention, and Campbell Family Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Blumberger, Thomson, Mulsant, Rajji, Maher, Daskalakis); the Monash Alfred Psychiatry research centre, The Alfred and Monash University Central Clinical School, Melbourne, Australia (Maller, Fitzgerald); Cancer Care Ontario and the Dalla Lana School of Public Health, University of Toronto, Toronto, Ont., Canada (Brown); the Toronto Western Hospital, University Health Network, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Downar); and the Non-Invasive Neurostimulation Therapies laboratory, Department of Psychiatry, University of British Columbia, Vancouver, B.C., Canada (Vila-Rodriguez).
Zafiris J
ZJ
Daskalakis
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D061218:Depressive Disorder, Treatment-Resistant / Q000628:therapy*; D005260:Female; D006801:Humans; D053783:Magnetic Resonance Imaging, Interventional / Q000379:methods; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D050781:Transcranial Magnetic Stimulation / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult