Vagus Nerve Stimulator battles drug resistant depression and more

Clinical and Investor Update

How can a nerve in your neck be recruited to combat depression and other maladies? The Vagus is an extremely long nerve that wanders from the brainstem (the part of the brain responsible for basic life functions such as heartbeat and breathing) all the way down to the bowels. A Vagus Nerve Stimulator (VNS) is a surgically implanted pacemaker-like device. A small, steel cylinder (shaped like a hockey-puck) is placed in a person’s chest, near the clavicle (collar bone) and contains a battery and sophisticated electronics (which can be controlled from outside the body). A wire electrode emanates from the puck, snakes under the skin and wraps around the Vagus nerve in the neck. The VNS device can be programmed to send various signals up from the nerve in the neck, through the skull and into the brain.

A pair of 2025 reports detail the power of VNS in combating drug resistant depression. A Multi Institutional consortium of scientists evaluated almost 500 people, who were suffering from depression. Not just regular depression, either. Their depression was severe and remained so despite various treatments such as multiple drugs and psychological counseling therapy. The doctors then randomly assigned patients to have their vagus nerve stimulated by the implanted electrodes or else undergo sham stimulation.

The researchers evaluated the patients over the course of a year’s time. Results showed that VNS, compared to sham stimulation, led to significant improvements in depressive symptoms, daily functioning, and quality of life. The treatment was well-tolerated, positioning VNS as a promising long-term intervention for treatment resistant depression, with benefits extending beyond symptom relief to enhance overall psychosocial outcomes.

VNS has also been used to fight numerous other maladies such as epilepsy, tinnitus, stroke, rheumatoid arthritis, multiple sclerosis, Crohn’s disease and diabetes. Some intrepid doctors also use VNS to control appetite in obesity (like ozempic, but without pills or injections). Others have pushed the VNS envelope as far as reversing heart failure, fighting the pain of fibromyalgia and the agony of migraines.

The total market size for VNS is currently estimated at 667 million dollars. The VNS market is projected to grow at a CAGR of 5.5–10.9% from 2023–2032, driven by epilepsy, depression, and emerging applications like stroke and inflammation. Implantable devices will continue to dominate, but non-invasive VNS is a challenge to future growth.

Let’s say you want to invest. Where can you put some cash to work? Several companies are involved in the production of implantable VNS. The key players include:

LivaNova, the gorilla in the VNS room, currently holds the largest market share, estimated at 50–60% of the implantable VNS market. This is due to their long-standing presence, extensive patient base (>125,000 treated), and approvals for epilepsy and depression. Cyberonics, once a pioneer in VNS for epilepsy, was gobbled up by LivaNova in 2015. Their legacy devices are now under LivaNova’s portfolio, which includes the ‘VNS Therapy System’ (e.g., SenTiva, SenTiva DUO). Their implantable VNS devices have FDA and CE Mark approvals for epilepsy and depression. LivaNova is publicly traded (NASDAQ: LIVN). Its current valuation is somewhere around two billion dollars.

MicroTransponder Inc produces the Vivistim Paired VNS System, FDA-approved in August 2021 for stroke rehabilitation. Specifically the Vivistim Paired VNS System targets moderate to severe upper extremity motor deficits (arm weakness) associated with chronic ischemic stroke, expanding the application of VNS beyond epilepsy and depression. MicroTransponder Inc. holds a 5–10% share of the implantable VNS market. MicroTransponder, not publicly traded, has an estimated value (based on typical valuations for medtech startups with a single approved product) ranging between likely 100–300 million dollars.

ReShape Lifesciences Inc. offers vBloc Therapy, an implantable VNS device initially developed for obesity management and related metabolic disorders. vBloc is also being explored for other indications. EnteroMedics initially developed vBloc VNS for obesity but is now integrated into ReShape. ReShape is currently estimated to garner 2–5% share of the implantable VNS market.ReShape Lifesciences is publicly traded on the NASDAQ under the ticker symbol RSLS. ReShape’s stock price has recently fallen 96% and current market cap is barely more than one million dollars.

SetPoint Medical Corporation is an emerging player with a focus on bioelectronic medicine for chronic inflammatory diseases. SetPoint is developing implantable VNS devices for inflammatory and autoimmune conditions, such as rheumatoid arthritis, multiple sclerosis and Crohn’s disease. The devices are in clinical trials and not yet widely commercialized. SetPoint isn’t publicly traded. The value is estimated at 50–150 million dollars based on venture funding rounds for bioelectronic medicine startups.

Beijing PINS Medical Co., Ltd. manufactures implantable VNS devices, primarily for the Chinese market, targeting epilepsy and other neurological disorders. Any valuation would be speculative due to regional focus.

BioControl Medical, Ltd. has developed an implantable VNS device called the CardioFit System, designed specifically for the treatment of chronic heart failure. CardioFit is not FDA-approved in the U.S., though it has received CE Mark in Europe (December 2008) for heart failure treatment. Biocontrol has suffered disappointing results from the INOVATE-HF Trial (2016): A phase III randomized trial (707 patients, 85 centers) tested CardioFit VNS against medical therapy. Terminated early as it failed to meet the primary efficacy endpoint (no significant reduction in death or heart failure. BioControl is privately held with a small market presence.

Want to learn more about VNS? Check out https://brain2mind.substack.com/p/a-nerve-in-your-neck-joins-the-fight