title: Double-blind optimization of subcallosal cingulate deep brain stimulation for treatment-resistant depression: a pilot study.
abstract: BACKGROUND
  Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is reported to be a safe and effective new treatment for treatment-resistant depression (TRD). However, the optimal electrical stimulation parameters are unknown and generally selected by trial and error. This pilot study investigated the relationship between stimulus parameters and clinical effects in SCC-DBS treatment for TRD.
  
  
  METHODS
  Four patients with TRD underwent SCC-DBS surgery. In a double-blind stimulus optimization phase, frequency and pulse widths were randomly altered weekly, and corresponding changes in mood and depression were evaluated using a visual analogue scale (VAS) and the 17-item Hamilton Rating Scale for Depression (HAM-D-17). In the open-label postoptimization phase, depressive symptoms were evaluated biweekly for 6 months to determine long-term clinical outcomes.
  
  
  RESULTS
  Longer pulse widths (270-450 μs) were associated with reductions in HAM-D-17 scores in 3 patients and maximal happy mood VAS responses in all 4 patients. Only 1 patient showed acute clinical or mood effects from changing the stimulation frequency. After 6 months of open-label therapy, 2 patients responded and 1 patient partially responded.
  
  
  CONCLUSIONS
  Limitations include small sample size, weekly changes in stimulus parameters, and fixed-order and carry-forward effects.
  
  
  CONCLUSIONS
  Longer pulse width stimulation may have a role in stimulus optimization for SCC-DBS in TRD. Longer pulse durations produce larger apparent current spread, suggesting that we do not yet know the optimal target or stimulus parameters for this therapy. Investigations using different stimulus parameters are required before embarking on large-scale randomized sham-controlled trials.
authors.affiliation: Department of Psychiatry and Clinical Neurosciences, Faculty of Medicine, University of Calgary, Hotchkiss Brain Institute, Calgary, Alta., Canada. rramasub@ucalgary.ca
authors.forename: Rajamannar
authors.initials: R
authors.lastname: Ramasubbu
authors.forename: Susan
authors.initials: S
authors.lastname: Anderson
authors.forename: Angela
authors.initials: A
authors.lastname: Haffenden
authors.forename: Swati
authors.initials: S
authors.lastname: Chavda
authors.forename: Zelma H T
authors.initials: ZH
authors.lastname: Kiss
mesh_terms: D046690:Deep Brain Stimulation / Q000592:standards*; D061218:Depressive Disorder, Treatment-Resistant / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006179:Gyrus Cinguli / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects