title: A patient-level meta-analysis of studies evaluating vagus nerve stimulation therapy for treatment-resistant depression.
abstract: OBJECTIVE
  To compare response and remission rates in depressed patients with chronic treatment-resistant depression (TRD) treated with vagus nerve stimulation (VNS) Therapy(®) plus treatment as usual (VNS + TAU) or TAU alone in a meta-analysis using Bayesian hierarchical models.
  
  
  METHODS
  Six outpatient, multicenter, clinical trials that have evaluated VNS + TAU or TAU in TRD, including two single-arm studies of VNS + TAU (n = 60 and n = 74), a randomized study of VNS + TAU versus TAU (n = 235), a randomized study of VNS + TAU comparing different VNS stimulation intensities (n = 331), a nonrandomized registry of VNS + TAU versus TAU (n = 636), and a single-arm study of TAU (n = 124) to provide longer-term, control data for comparison with VNS-treated patients.
  
  
  METHODS
  A systematic review of individual patient-level data based on the intent-to-treat principle, including all patients who contributed more than one post-baseline visit. Response was based on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions scale's Improvement subscale (CGI-I), as these were the two clinician-rated measures common across all or most studies. Remission was based on the MADRS.
  
  
  RESULTS
  Outcomes were compared from baseline up to 96 weeks of treatment with VNS + TAU (n = 1035) versus TAU (n = 425). The MADRS response rate for VNS + TAU at 12, 24, 48, and 96 weeks were 12%, 18%, 28%, and 32% versus 4%, 7%, 12%, and 14% for TAU. The MADRS remission rate for VNS + TAU at 12, 24, 48, and 96 weeks were 3%, 5%, 10%, and 14% versus 1%, 1%, 2%, and 4%, for TAU. Adjunctive VNS Therapy was associated with a greater likelihood of response (odds ratio [OR] = 3.19, 95% confidence interval [CI]: 2.12, 4.66) and remission (OR = 4.99, CI: 2.93, 7.76), compared with TAU. For patients who had responded to VNS + TAU at 24 weeks, sustained response was more likely at 48 weeks (OR = 1.98, CI: 1.34, 3.01) and at 96 weeks (OR = 3.42, CI: 1.78, 7.31). Similar results were observed for CGI-I response.
  
  
  CONCLUSIONS
  For patients with chronic TRD, VNS + TAU has greater response and remission rates that are more likely to persist than TAU.
authors.affiliation: Berry Consultants, Austin, TX, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Berry
authors.forename: Kristine
authors.initials: K
authors.lastname: Broglio
authors.forename: Mark
authors.initials: M
authors.lastname: Bunker
authors.forename: Amara
authors.initials: A
authors.lastname: Jayewardene
authors.forename: Bryan
authors.initials: B
authors.lastname: Olin
authors.forename: A John
authors.initials: AJ
authors.lastname: Rush
keywords: Bayesian meta-analysis; VNS Therapy; remission rate; response rate; treatment-resistant depression; vagus nerve stimulation