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

Figures & data

Table 1 Clinical Trials and Meta-Analyses of Vagus Nerve Stimulation (VNS) in the Treatment of Major Depressive Episodes

Study	Publication	VNS+TAU (N)	TAU (N)	Design	Study Duration and Follow-Up
D-01	Rush et al. (2000);^Citation16 Sackeim et al. (2001)^Citation17	60	–	Open-label, prospective, single arm	24 months
D-02	Rush et al. (2005)^Citation15	235	–	RCT, sham-controlled (10 weeks), then single arm, open label	24 months
D-03	Schlaepfer et al. (2008)^Citation49 Bajbouj et al. (2010)^Citation50	74	–	Open-label, prospective, single arm	24 months
D-04	George et al. (2005)^Citation51		124	Open-label, prospective, single arm	24 months
D-21	Aaronson et al. (2013)^Citation75	331	–	RCT of VNS dosing (3 arms)	12 months
D-23	Aaronson et al. (2017)^Citation18	335	301	Open label, two arm, prospective registry	60 months
Meta-analysis	Berry et al. (2013)^Citation20	1035	425	Meta-analysis of D-01, D-02, D-03, D-04, D-21, D-23	–
Combined D-21 and D-23 with 5 year follow-up	Aaronson et al. (2017)^Citation18	494	301	Open label, two arm, prospective registry	60 months
Meta-analysis	Bottomley et al. (2020)^Citation19	1171	409	Meta-analysis of 22 studies	–

Notes: The D-prefix in the study identifier indicates that the study population comprised depressed patients, and the subsequent number identifies the particular study within this indication. For example, D-01 was the first, pilot study of VNS in treatment-resistant depression using the NeuroCybernetic Prosthesis (NCP^®) System (LivaNova USA, Inc.).

Abbreviations: VNS, vagus nerve stimulation; TAU, treatment-as-usual; RCT, randomized controlled trial.

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