title: Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial.
abstract: 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.
authors.affiliation: Brain Stimulation Division, Department of Psychiatry, Medical University of South Carolina, Charleston, SC 29425, USA. georgem@musc.edu
authors.forename: Mark S
authors.initials: MS
authors.lastname: George
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Lisanby
authors.forename: David
authors.initials: D
authors.lastname: Avery
authors.forename: William M
authors.initials: WM
authors.lastname: McDonald
authors.forename: Valerie
authors.initials: V
authors.lastname: Durkalski
authors.forename: Martina
authors.initials: M
authors.lastname: Pavlicova
authors.forename: Berry
authors.initials: B
authors.lastname: Anderson
authors.forename: Ziad
authors.initials: Z
authors.lastname: Nahas
authors.forename: Peter
authors.initials: P
authors.lastname: Bulow
authors.forename: Paul
authors.initials: P
authors.lastname: Zarkowski
authors.forename: Paul E
authors.initials: PE
authors.lastname: Holtzheimer
authors.forename: Theresa
authors.initials: T
authors.lastname: Schwartz
authors.forename: Harold A
authors.initials: HA
authors.lastname: Sackeim
mesh_terms: 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