Clinical issues in considering vagus nerve stimulation for treatment-resistant depression.

This review briefly discusses the clinical and basic science rationale for vagus nerve stimulation (VNS) in treatment-resistant depression (TRD). As the number of treatment failures for depression increases, the likelihood of achieving remission during acute treatment decreases, and the risk of relapse increases with the number of treatment failures. Two open trials of adjunctive VNS for TRD showed positive acute results and a growing benefit over time. The results of the acute randomized controlled trial were not significant for the primary outcome (response by HRSD-24), but the secondary measure (IDS-SR-30) was significant for VNS. A 12-month nonrandomized comparative analysis of patients receiving adjunctive VNS with TRD patients receiving treatment as usual showed significant results favoring VNS. Post hoc analyses found that this difference was not accounted for baseline differences nor by intercurrent treatment. While VNS is well tolerated, the optimal dosing strategies have not been determined nor have clinically useful predictors of who will respond to the treatment. Given the profound effects of TRD upon the daily lives of patients and that a substantial number of VNS patients receive benefit, VNS is a useful option for managing patients with TRD.