title: Two Versus One High-Frequency Repetitive Transcranial Magnetic Stimulation Session per Day for Treatment-Resistant Depression: A Randomized Sham-Controlled Trial.
abstract: OBJECTIVE
  High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has proven antidepressant effects, but the optimal frequency of sessions remains unclear.
  
  
  METHODS
  We conducted a 3-week, sham-controlled trial to assess the antidepressant efficacy of 1 active HF-rTMS session per day (A1 group) compared with 2 per day (A2 group) and equivalent sham sessions (once a day, S1 group; twice a day, S2 group) in patients with treatment-resistant major depression with a subsequent 2-week follow-up period. One hundred seventy-seven patients were screened, of whom 105 met eligibility criteria and 98 consented and were randomized. The HF-rTMS (20 Hz) was targeted to the left prefrontal cortex in sessions of approximately 40 trains (2 seconds each) at 100% resting motor threshold with an intertrain interval of 1 minute. Treatment response was defined as a 50% or greater decrease in the Hamilton Depression Rating Scale (HDRS) score and/or Clinician Global Impressions-Severity of Illness (CGI-S) score of 3 or less. Remission was defined as HDRS score less than 8 and/or CGI-S score of 2 or less.
  
  
  RESULTS
  Practically none of the subjects in either sham groups achieved remission. Increased odds of remission were present for CGI-S by stimulating twice rather than once per day (odds ratio [OR] = 1.5, P = 0.018), whereas there was a marginal result for HDRS (OR = 3.9, P = 0.066). Patients who had lower baseline HDRS (OR = 0.75, P = 0.014) and CGI-S scores (OR = 0.18, P = 0.001) were more likely to achieve remission.
  
  
  CONCLUSIONS
  Twice per day active HF-rTMS might be more effective than once per day active HF-rTMS or sham stimulation.
authors.affiliation: From the *First Department of Psychiatry, National and Kapodistrian University of Athens, Eginition Hospital, Athens, Greece; Departments of †Psychosis Studies, and ‡Biostatistics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; §University of Athens Medical School, Center for Health Services Research, Athens, Greece; and ∥The Johns Hopkins University, Baltimore, MD.
authors.forename: Christos
authors.initials: C
authors.lastname: Theleritis
authors.forename: Pavlos
authors.initials: P
authors.lastname: Sakkas
authors.forename: Thomas
authors.initials: T
authors.lastname: Paparrigopoulos
authors.forename: Silia
authors.initials: S
authors.lastname: Vitoratou
authors.forename: Chara
authors.initials: C
authors.lastname: Tzavara
authors.forename: Stefania
authors.initials: S
authors.lastname: Bonaccorso
authors.forename: Antonios
authors.initials: A
authors.lastname: Politis
authors.forename: Constantin R
authors.initials: CR
authors.lastname: Soldatos
authors.forename: Costantin
authors.initials: C
authors.lastname: Psarros
mesh_terms: D000293:Adolescent; D000328:Adult; D003865:Major Depressive Disorder / Q000628:therapy; D061218:Depressive Disorder, Treatment-Resistant / Q000523:psychology / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex; D011569:Psychiatric Status Rating Scales; D050781:Transcranial Magnetic Stimulation / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult