I came across an article written recently concerning the use of Vagus Nerve Stimulation (VNS) to treat difficult-to-treat depression (DTD) and other mood disorders (Sackeim, et al. 2020). However, there is a conflict of interest with all the authors, as reported by PubMed:

Professor Sackeim serves as a scientific adviser to the MECTA Corporation and Neuronetics Inc., as well as LivaNova PLC, which manufactures the Vagus Nerve Stimulation Therapy® System. He receives honoraria and royalties from Elsevier, Inc. and Oxford University Press

Dr. Dibué is an employee of LivaNova PLC, manufacturer of vagus nerve stimulators and holds stock options.

Dr Bunker is a former employee and a current consultant of LivaNova USA PLC.

Professor Rush has received consulting fees from Akili, Brain Resource Inc., Compass Inc., Curbstone Consultant LLC, Emmes Corp., Holmusk, Johnson and Johnson (Janssen), LivaNova USA PLC, Neurocrine Biosciences Inc., Otsuka-US, and Sunovion; speaking fees from LivaNova; and royalties from Guilford Press and the University of Texas Southwestern Medical Center, Dallas, TX (for the Inventory of Depressive Symptoms and its derivatives). He is also named coinventor on two patents: US Patent No 7,795,033: Methods to Predict the Outcome of Treatment with Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S, Wilson AS; and US Patent No 7,906,283: Methods to Identify Patients at Risk of Developing Adverse Events During Treatment with Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S.

When looking at the "similar articles" at the bottom of Sackeim, et al. (2020), the bottom one doesn't seem relevant to me, but except for the 4th suggestion, they all have team members in the originating article who have conflicts of interest, and with the 4th one (Bottomley, et al. 2020):

J Bottomley, C LeReun, A Diamantopoulos and S Mitchell have received consultancy payments from LivaNova. B Gaynes has received consultation payments from LivaNova addressing models of treatment resistant depression.

Looking at Google Scholar,

the conduct of the study was partly funded by the manufacturer of the (VNS)TherapyTMSystem, Cyberonics Inc., Houston, TX, USA.

Dr. O'Reardon has received research support from and is on the speakers bureau for Cyberonics.

My question

Are there supporting research papers which are free from any conflicts of interest? What is the actual efficacy of VNS to treat depression?

I am after some research which has not had the possibility of being influenced by funders who have anything to do with the manufacture(s) of VNS equipment. All those I have seen so far have been funded wholly or in part by Cyberonics (now LivaNova) who manufacture the equipment used in the research. Basically it is like the related question I have asked before in MedicalSciences.SE but more refined where I am looking at the possibility that there could be research funded independently from those who would have a financial gain from said research.


Bottomley, J. M., LeReun, C., Diamantopoulos, A., Mitchell, S., & Gaynes, B. N. (2020). Vagus nerve stimulation (VNS) therapy in patients with treatment resistant depression: a systematic review and meta-analysis. Comprehensive psychiatry, 98, 152156. https://doi.org/10.1016/j.comppsych.2019.152156

O'Reardon, J. P., Cristancho, P., & Peshek, A. D. (2006). Vagus nerve stimulation (VNS) and treatment of depression: to the brainstem and beyond. Psychiatry (Edgmont), 3(5), 54. https://www.ncbi.nlm.nih.gov/pubmed/21103178

Sackeim, H. A., Dibué, M., Bunker, M. T., & Rush, A. J. (2020). The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders. Neuropsychiatric disease and treatment, 16, 3081-3093.

Schlaepfer, T. E., Frick, C., Zobel, A., Maier, W., Heuser, I., Bajbouj, M., ... & Hasdemir, M. (2008). Vagus nerve stimulation for depression: efficacy and safety in a European study. Psychological medicine, 38(5), 651-61. https://doi.org/10.1017/S0033291707001924


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