title: Repetitive transcranial magnetic stimulation (rTMS) at high and low frequency: an efficacious therapy for major drug-resistant depression?
abstract: OBJECTIVE
  Repetitive transcranial magnetic stimulation (rTMS) is proposed for the treatment of drug-resistant depression. Studies performed in accordance with evidence-based medicine (EBM) are scarce, particularly in seeking optimal treatment and evaluation parameters. We aimed to test various types of rTMS in a large sample of depressed patients following EBM rules and to investigate treatment-related changes in plasma levels of neurotransmitters involved in depression.
  
  
  METHODS
  Seventy-one drug-resistant depressed patients were randomly assigned to low (1 Hz) or high (17 Hz) rate TMS, applied for 5 days over the left dorsolateral prefrontal cortex (L-DLPFC). Patients were separated into two study designs. One group (20 patients) received only active treatment, while the other entered a double-blind, placebo-controlled, crossover design. Pre- and post-treatment blood samples were taken for evaluation of plasma levels of dopamine and serotonin.
  
  
  RESULTS
  After a week of treatment patients had a measurable benefit. However, overall the placebo stimulation did not differ significantly from real stimulation, nor were differences observed between the two rates of rTMS. The only difference emerged when the real stimulation was applied at 17 Hz following placebo treatment. Plasma levels of neurotransmitters between active and placebo rTMS were similar.
  
  
  CONCLUSIONS
  Using the treatment schedule of 1 week, although a clinical improvement after active treatment was indeed observed, this was both clinically and biochemically indistinguishable from that seen in the placebo arm.
  
  
  CONCLUSIONS
  This suggests that most of the previous emphasis, for short period of treatment, should be tempered down and that further work is required in order to verify whether optimal stimulation and evaluation parameters for TMS-treatment of depression beyond the placebo effect may be found following EBM rules.
authors.affiliation: IRCCS San Giovanni di Dio-FBF, Brescia, Italy. c.miniussi@oh-fbf.it
authors.forename: C
authors.initials: C
authors.lastname: Miniussi
authors.forename: C
authors.initials: C
authors.lastname: Bonato
authors.forename: S
authors.initials: S
authors.lastname: Bignotti
authors.forename: A
authors.initials: A
authors.lastname: Gazzoli
authors.forename: M
authors.initials: M
authors.lastname: Gennarelli
authors.forename: P
authors.initials: P
authors.lastname: Pasqualetti
authors.forename: G B
authors.initials: GB
authors.lastname: Tura
authors.forename: M
authors.initials: M
authors.lastname: Ventriglia
authors.forename: P M
authors.initials: PM
authors.lastname: Rossini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D003865:Major Depressive Disorder / Q000628:therapy*; D004298:Dopamine / Q000097:blood; D004351:Drug Resistance; D004599:Electric Stimulation Therapy / Q000379:methods; D005260:Female; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D012701:Serotonin / Q000097:blood; D050781:Transcranial Magnetic Stimulation; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid