The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders.

The history of VNS in DTD has implications for interventional studies in this population, and perhaps other chronic medical disorders. The slow onset of benefit with VNS necessitates considerably longer controlled observation periods to establish efficacy. Durability of benefit should be routinely incorporated in efficacy assessment. New outcome metrics are needed to both categorically identify clinically meaningful benefit and to integrate information on symptom burden over time.