title: Epidural cortical stimulation of the left dorsolateral prefrontal cortex for refractory major depressive disorder.
abstract: BACKGROUND
  A significant number of patients with major depressive disorder are unresponsive to conventional therapies. For these patients, neuromodulation approaches are being investigated.
  
  
  OBJECTIVE
  To determine whether epidural cortical stimulation at the left dorsolateral prefrontal cortex is safe and efficacious for major depressive disorder through a safety and feasibility study.
  
  
  METHODS
  Twelve patients were recruited in this randomized, single-blind, sham-controlled study with a 104-week follow-up period. The main outcome measures were Hamilton Depression Rating Scale-28 (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), Global Assessment of Function (GAF), and Quality of Life Enjoyment and Satisfaction (QLES) questionnaire. An electrode was implanted over Brodmann area 9/46 in the left hemisphere. The electrode provided long-term stimulation to this target via its connections to an implanted neurostimulator in the chest.
  
  
  RESULTS
  During the sham-controlled phase, there was no statistical difference between sham and active stimulation, although a trend toward efficacy was seen with the active stimulation group. In the open-label phase, we observed a significant improvement in outcome scores for the HDRS, MADRS, and GAF but not the QLES (HDRS: df = 7, F = 7.72, P < .001; MADRS: df = 7, F = 8.2, P < .001; GAF: df = 5, F = 16.87, P < .001; QLES: df = 5, F = 1.32, P > .2; repeated measures ANOVA). With regard to the HDRS, 6 patients had ≥ 40% improvement, 5 patients had ≥ 50% improvement, and 4 subjects achieved remission (HDRS < 10) at some point during the study.
  
  
  CONCLUSIONS
  Epidural cortical stimulation of the left dorsolateral prefrontal cortex appears to be a safe and potentially efficacious neuromodulation approach for treatment-refractory major depressive disorder.
authors.affiliation: Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. bkopell@mcw.edu
authors.forename: Brian Harris
authors.initials: BH
authors.lastname: Kopell
authors.forename: Jerry
authors.initials: J
authors.lastname: Halverson
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Butson
authors.forename: Mercedes
authors.initials: M
authors.lastname: Dickinson
authors.forename: Julie
authors.initials: J
authors.lastname: Bobholz
authors.forename: Harold
authors.initials: H
authors.lastname: Harsch
authors.forename: Charles
authors.initials: C
authors.lastname: Rainey
authors.forename: Douglas
authors.initials: D
authors.lastname: Kondziolka
authors.forename: Robert
authors.initials: R
authors.lastname: Howland
authors.forename: Emad
authors.initials: E
authors.lastname: Eskandar
authors.forename: Karleyton C
authors.initials: KC
authors.lastname: Evans
authors.forename: Darin D
authors.initials: DD
authors.lastname: Dougherty
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D004599:Electric Stimulation Therapy / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000502:physiology* / Q000601:surgery; D011446:Prospective Studies; D011877:Radionuclide Imaging; D016037:Single-Blind Method