title: A randomized double-blind crossover trial of deep brain stimulation of the subcallosal cingulate gyrus in patients with treatment-resistant depression: a pilot study of relapse prevention.
abstract: BACKGROUND
  To date, antidepressant drugs show limited efficacy, leaving a large number of patients experiencing severe and persistent symptoms of major depression. Previous open-label clinical trials have reported significant sustained improvements with deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG) in patients with severe, chronic treatment-resistant depression (TRD). This study aimed to confirm the efficacy and measure the impact of discontinuation of the electrical stimulation.
  
  
  METHODS
  We conducted a 6-month double-blind, randomized, sham-controlled crossover study in implanted patients with previous severe TRD who experienced full remission after chronic stimulation. After more than 3 months of stable remission, patients were randomly assigned to 2 treatment arms: the ON-OFF arm, which involved active electrode stimulation for 3 months followed by sham stimulation for 3 months, and the OFF-ON arm, which involved sham stimulation for 3 months followed by active stimulation for 3 months. The primary outcome measure was the difference in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score between sham and active stimulation.
  
  
  RESULTS
  We enrolled 5 patients in our trial. A Friedman repeated-measures analysis of variance revealed a significant effect of treatment (χ(2)1 = 5.0, p = 0.025) in patients with higher depression scores during sham stimulation. At the end of active stimulation, depression was remitted in 4 of 5 patients and none of them had experienced a relapse, whereas at the end of sham stimulation, 2 patients remained in remission, 2 relapsed and 1 showed a progressive worsening without reaching relapse criteria.
  
  
  CONCLUSIONS
  The small sample size limited the statistical power and external validity.
  
  
  CONCLUSIONS
  These preliminary findings indicate that DBS of the SCG is an effective and safe treatment for severe forms of TRD and that continuous electrical stimulation is required to maintain therapeutic effects.
  
  
  BACKGROUND
  NCT01268137 (ClinicalTrials.gov).
authors: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Dolors
authors: D
authors: Puigdemont
authors: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Maria
authors: M
authors: Portella
authors: From the Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Rosario
authors: R
authors: Pérez-Egea
authors: Department of Neurosurgery, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Joan
authors: J
authors: Molet
authors: Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Alexandre
authors: A
authors: Gironell
authors: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Javier
authors: J
authors: de Diego-Adeliño
authors: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Anna
authors: A
authors: Martín
authors: Department of Neurosurgery, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Rodrigo
authors: R
authors: Rodríguez
authors: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Enric
authors: E
authors: Àlvarez
authors: Department of Neurochemistry and Neuropharmacology, Institut d'Investigacions Biomèdiques de Barcelona, IDIBAPS, Consejo Superior de Investigaciones Cientificas, IDIBAPS, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain.
authors: Francesc
authors: F
authors: Artigas
authors: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Víctor
authors: V
authors: Pérez
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D046690:Deep Brain Stimulation / Q000379:methods*; D003865:Major Depressive Disorder / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006179:Gyrus Cinguli / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D055502:Secondary Prevention / Q000379:methods; D016896:Treatment Outcome
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