• A prospective, multi-center randomized, controlled, blinded trial of vagus nerve stimulation for difficult to treat depression: A novel design for a novel treatment.

      Conway, Charles R; Olin, Bryan; Aaronson, Scott T; Sackeim, Harold A; Bunker, Mark; Kriedt, Christopher; Greco, Theresa; Broglio, Kristine; Vestrucci, Matteo; Rush, A John (Elsevier Ltd., 2020-06-19)
      Few treatment options exist for patients with difficult-to-treat depression (DTD). One potentially efficacious treatment is vagus nerve stimulation (VNS): chronic stimulation of the vagus nerve using an implanted stimulator. Given a series of recent VNS clinical studies, including a large, five-year naturalistic investigation, the Center for Medicare and Medicaid Services (CMS) reconsidered the previous non coverage determination and announced coverage for patients participating in a “coverage with evidence” trial. This study, entitled, A PRospective, Multi-cEnter, Randomized Controlled Blinded Trial DemOnstrating the Safety and Effectiveness of VNS Therapy® System as AdjunctivE Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression (RECOVER), includes DTD patients with at least four unsuccessful antidepressant treatments in the current episode and will randomize both unipolar and bipolar DTD participants, each up to 500 evaluable enrollees. Predetermined interim analyses will define the necessary sample size. All participants will be implanted with VNS devices: half receive active stimulation during year one, and half receive delayed stimulation after year one. Participants will be followed for 5 years. This RCT is unique for DTD studies: 1) large sample size and long study duration (one year of controlled comparison); 2) use of a percent time in response as the primary outcome measure, given the chronic illness and its fluctuating course (vis-à-vis meeting a response criteria at a single time point); 3) inclusion of diverse measures of VNS impact on function, including quality of life, degree of disability, health status, and suicidality.
    • A retrospective analysis of bipolar depression treated with transcranial magnetic stimulation

      Goldwaser, Eric L; Daddario, Kathy; Aaronson, Scott T (John Wiley and Sons Inc., 2020-11-10)
      Introduction: Treatment options are limited for patients with bipolar depression. Antidepressants added to mood stabilizers even carry risks of precipitating mixed/manic episodes. Transcranial magnetic stimulation (TMS) may provide a safe and effective option for these patients. Methods: Database analysis of the TMS Service at Sheppard Pratt Health System identified patients with bipolar disorder type I (BD1) or II (BD2) in a pure depressive phase at initiation of TMS. Records were reviewed for response and remission rates based on MADRS scores, time to effect, and adverse events, notably treatment-emergent affective switching. All had failed at least two prior treatments for depression, were currently on at least one mood stabilizer and off antidepressants. Stimulation parameters targeted left dorsolateral prefrontal cortex: 120% motor threshold, 10 pulses per second (pps) × 4s, intertrain interval (ITI) 26s, 75 trains (37.5 min/session) for 3,000 pps total, 5 sessions/week for 30 total treatments, or until remission criteria were met. Results: A total of 44 patients with BD were identified, representing 15% of the total TMS population. 77% of those who completed a course of TMS met response criteria, and 41% of subjects who completed at least 25 treatments met remission criteria. Subjects with BD1 were more likely to respond, remit, or suffer an adverse event than those with BD2. No patient met clinical criteria for a manic/mixed episode, but four (10%) discontinued due to concerns of activation. Conclusions: TMS is effective in the bipolar depressed population where episode focused intervention can be specifically offered. Risk of psychomotor agitation must be closely monitored.