Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial.
BACKGROUND
Daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) has been studied as a potential treatment for depression, but previous work had mixed outcomes and did not adequately mask sham conditions.


OBJECTIVE
To test whether daily left prefrontal rTMS safely and effectively treats major depressive disorder.


METHODS
Prospective, multisite, randomized, active sham-controlled (1:1 randomization), duration-adaptive design with 3 weeks of daily weekday treatment (fixed-dose phase) followed by continued blinded treatment for up to another 3 weeks in improvers.


METHODS
Four US university hospital clinics.


METHODS
Approximately 860 outpatients were screened, yielding 199 antidepressant drug-free patients with unipolar nonpsychotic major depressive disorder.


METHODS
We delivered rTMS to the left prefrontal cortex at 120% motor threshold (10 Hz, 4-second train duration, and 26-second intertrain interval) for 37.5 minutes (3000 pulses per session) using a figure-eight solid-core coil. Sham rTMS used a similar coil with a metal insert blocking the magnetic field and scalp electrodes that delivered matched somatosensory sensations.


METHODS
In the intention-to-treat sample (n = 190), remission rates were compared for the 2 treatment arms using logistic regression and controlling for site, treatment resistance, age, and duration of the current depressive episode.


RESULTS
Patients, treaters, and raters were effectively masked. Minimal adverse effects did not differ by treatment arm, with an 88% retention rate (90% sham and 86% active). Primary efficacy analysis revealed a significant effect of treatment on the proportion of remitters (14.1% active rTMS and 5.1% sham) (P = .02). The odds of attaining remission were 4.2 times greater with active rTMS than with sham (95% confidence interval, 1.32-13.24). The number needed to treat was 12. Most remitters had low antidepressant treatment resistance. Almost 30% of patients remitted in the open-label follow-up (30.2% originally active and 29.6% sham).


CONCLUSIONS
Daily left prefrontal rTMS as monotherapy produced statistically significant and clinically meaningful antidepressant therapeutic effects greater than sham.


BACKGROUND
clinicaltrials.gov Identifier: NCT00149838.
George
Mark S
MS
Brain Stimulation Division, Department of Psychiatry, Medical University of South Carolina, Charleston, SC 29425, USA. georgem@musc.edu
Lisanby
Sarah H
SH
Avery
David
D
McDonald
William M
WM
Durkalski
Valerie
V
Pavlicova
Martina
M
Anderson
Berry
B
Nahas
Ziad
Z
Bulow
Peter
P
Zarkowski
Paul
P
Holtzheimer
Paul E
PE
Schwartz
Theresa
T
Sackeim
Harold A
HA
D000328:Adult; D000368:Aged; D003865:Major Depressive Disorder / Q000503:physiopathology* / Q000628:therapy*; D004292:Dominance, Cerebral / Q000502:physiology; D004311:Double-Blind Method; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000503:physiopathology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult