title: Repetitive transcranial magnetic stimulation (rTMS) in combination with escitalopram in patients with treatment-resistant major depression: a double-blind, randomised, sham-controlled trial.
abstract: BACKGROUND
  The role of high-frequency rTMS over the left cortex as an add-on strategy in the treatment of major depression is still uncertain even in patients resistant to pharmacotherapy. We had planned a large sham TMS controlled study in the acute phase with a placebo-controlled relapse-prevention phase with escitalopram. However, because a recent meta-analysis showed only a small effect size of rTMS over sham TMS in the acute treatment phase of depressed patients, we decided to make an interim analysis.
  
  
  METHODS
  In patients with medication-resistant major depression we administered in a randomised trial 15 sessions of sham-controlled rTMS over three weeks in combination with 20 mg escitalopram daily. After the last rTMS, the patients were followed for another 9 weeks on 20 mg escitalopram daily. The antidepressant effect was measured by the HAM-D(6) as primary outcome scale.
  
  
  RESULTS
  A total of 45 patients with complete data were randomised so that 23 patients received sham TMS and 22 patients received active, high-frequency rTMS over the left cortex. Over the 3 weeks, the active rTMS treatment was superior to sham TMS with effect sizes on the HAM-D(6) above 0.70, which indicates not only a statistically but also a clinically significant effect. The patients had typically been through two failed antidepressant treatment attempts with non-tricyclics before inclusion in the study. Both the rTMS and escitalopram were well-tolerated.
  
  
  CONCLUSIONS
  High-frequency rTMS over the left cortex is an add-on strategy of clinical significance in combination with escitalopram in patients with major depression resistant to non-tricyclic antidepressants.
authors.affiliation: Psychiatric Research Unit, Frederiksborg General Hospital, Hillerød, Denmark.
authors.forename: L G
authors.initials: LG
authors.lastname: Bretlau
authors.forename: M
authors.initials: M
authors.lastname: Lunde
authors.forename: L
authors.initials: L
authors.lastname: Lindberg
authors.forename: M
authors.initials: M
authors.lastname: Undén
authors.forename: S
authors.initials: S
authors.lastname: Dissing
authors.forename: P
authors.initials: P
authors.lastname: Bech
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000628:therapy*; D004311:Double-Blind Method; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D050781:Transcranial Magnetic Stimulation; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram