Beyond the primary outcome: Why the RECOVER trial for vagus nerve stimulation matters in treatment-resistant depression.

In this latest issue of Brain Stimulation, two important papers on the use of vagus nerve stimulation (VNS) in adults with markedly TRD have been published, reporting on the findings of the RECOVER study. This was a commercially sponsored, one-year, randomized controlled trial that assessed the efficacy and safety of active versus sham VNS as an add-on therapy to treatment as usual in 493 adults with marked TRD; a parallel study in bipolar depression is underway. These papers also provide some perspective on several important areas. Foremost among these is that even though patients were required to have treatment resistant depression to enter this study, the field still lacks good operational definition of treatment resistance (much less a biological definition). Longer-term management of implanted systems is a challenge for our future, and how we as a field provide guidance to patients across these interventions requires considerable attention.