Effects of vagus nerve stimulation on daily function and quality of life in markedly treatment-resistant major depression: Findings from a one-year, randomized, sham-controlled trial

Brain Stimul. 2024 Dec 18:S1935-861X(24)01382-2. doi: 10.1016/j.brs.2024.12.1187. Online ahead of print.

Abstract

Background: Depression treatments aim to minimize symptom burden and optimize quality of life (QoL) and psychosocial function.

Objective: Compare the effects of adjunctive versus sham vagus nerve stimulation (VNS) on QoL and function in markedly treatment-resistant depression (TRD).

Methods: In this multicenter, double-blind, sham-controlled trial, 493 adults with TRD and ≥4 adequate but unsuccessful antidepressant treatment trials (current episode) were randomized to active (n = 249) or sham (n = 244) VNS (plus treatment as usual) over a 12-month observation period. Quarterly outcomes included QoL with the Q-LES-Q, Mini-Q-LES-Q, and EQ-5D-5L, and function with the WHODAS 2.0 and Work Productivity and Activity Impairment Questionnaire (WPAI) item 6. Differences between treatment groups in change in scores from baseline and percentage of time with a meaningful response in Q-LES-Q, Mini-Q-LES-Q, and WPAI item 6 scores were analyzed.

Results: Active VNS was superior to sham in mean change in scores from baseline in the Mini-Q-LES-Q (P = 0.050) and WPAI item 6 (health condition's effect on regular activities [P = 0.050]) used as continuous variables, with a similar trend for Q-LES-Q (P = 0.061). Active VNS was superior to sham in time spent in clinically meaningful benefit (categorical analyses) using the Q-LES-Q (P = 0.029), Mini-Q-LES-Q (P = 0.011), and WPAI item 6 (P = 0.039). The WHODAS 2.0 (P = 0.304) and EQ-5D visual analog scale (P = 0.125) failed to reveal between-group differences.

Conclusion: Active VNS was superior to sham VNS in improving QoL and psychosocial function in patients with TRD. VNS has a broader therapeutic impact than symptom improvement alone in patients with marked psychosocial impairment.

Keywords: Efficacy; Function; Quality of life; RECOVER trial; Treatment-resistant depression; Vagus nerve stimulation.