title: Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial.
abstract: BACKGROUND
  We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression.
  
  
  METHODS
  In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD.
  
  
  RESULTS
  Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain.
  
  
  CONCLUSIONS
  Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Philadelphia, PA 19014, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: O'Reardon
authors.forename: H Brent
authors.initials: HB
authors.lastname: Solvason
authors.forename: Philip G
authors.initials: PG
authors.lastname: Janicak
authors.forename: Shirlene
authors.initials: S
authors.lastname: Sampson
authors.forename: Keith E
authors.initials: KE
authors.lastname: Isenberg
authors.forename: Ziad
authors.initials: Z
authors.lastname: Nahas
authors.forename: William M
authors.initials: WM
authors.lastname: McDonald
authors.forename: David
authors.initials: D
authors.lastname: Avery
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fitzgerald
authors.forename: Colleen
authors.initials: C
authors.lastname: Loo
authors.forename: Mark A
authors.initials: MA
authors.lastname: Demitrack
authors.forename: Mark S
authors.initials: MS
authors.lastname: George
authors.forename: Harold A
authors.initials: HA
authors.lastname: Sackeim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001299:Audiometry; D003865:Major Depressive Disorder / Q000523:psychology / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D050781:Transcranial Magnetic Stimulation / Q000009:adverse effects / Q000295:instrumentation; D016896:Treatment Outcome