title: Deep brain stimulation to the medial forebrain bundle for depression- long-term outcomes and a novel data analysis strategy.
abstract: Deep brain stimulation (DBS) of the supero-lateral branch of the medial forebrain bundle (slMFB) in treatment-resistant depression (TRD) is associated with acute antidepressant effects.
  
  
  
  Long-term clinical effects including changes in quality of life, side effects and cognition as well as long-term data covering four years are assessed.
  
  
  
  Eight TRD patients were treated with DBS bilateral to the slMFB. Primary outcome measure was a 50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) (response) and remission (MADRS <10) at 12 months compared to baseline. Secondary measures were anxiety, general functioning, quality of life, safety and cognition assessed for 4 years. Data is reported as conventional endpoint-analysis and as area under the curve (AUC) timeline analysis.
  
  
  
  Six of eight patients (75%) were responders at 12 months, four patients reached remission. Long-term results revealed a stable effect up to four years. Antidepressant efficacy was also reflected in the global assessment of functioning. Main side effect was strabismus at higher stimulation currents. No change in cognition was identified. AUC analysis revealed a significant reduction in depression for 7/8 patients in most months.
  
  
  
  Long-term results of slMFB-DBS suggest acute and sustained antidepressant effect; timeline analysis may be an alternative method reflecting patient's overall gain throughout the study. Being able to induce a rapid and robust antidepressant effect even in a small, sample of TRD patients without significant psychiatric comorbidity, render the slMFB an attractive target for future studies.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Germany.
authors.forename: Bettina H
authors.initials: BH
authors.lastname: Bewernick
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kayser
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Germany.
authors.forename: Sabrina M
authors.initials: SM
authors.lastname: Gippert
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Switala
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, University Hospital Freiburg, Germany.
authors.forename: Volker A
authors.initials: VA
authors.lastname: Coenen
authors.affiliation: Division of Interventional Biological Psychiatry, University Hospital Freiburg, Germany; Departments of Psychiatry and Mental Health, The Johns Hopkins University, Baltimore, MD, USA. Electronic address: schlaepf@jhmi.edu.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Schlaepfer
mesh_terms: D000328:Adult; D003071:Cognition; D046690:Deep Brain Stimulation / Q000009:adverse effects / Q000379:methods*; D061218:Depressive Disorder, Treatment-Resistant / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology*; D008875:Middle Aged
keywords: Cognition; Deep brain stimulation; Depression; Long-term follow-up; Medial forebrain bundle; Timeline analysis