Vagus Nerve Stimulation for Depression: How VNS Works and Who It’s For

Key takeaways

• Vagus nerve stimulation (VNS) for depression uses an implanted device to stimulate the vagus nerve, sending signals to brain regions that regulate mood.
• VNS is a long-term treatment for chronic or treatment-resistant depression (TRD), indicated for adults who haven’t responded adequately to four or more antidepressant treatments.
• It’s not a quick fix. Benefits can take several months, and some people may continue improving after a year.
• The research is nuanced. While some trials have had mixed results, longer-term studies suggest VNS can improve symptoms, functioning, and quality of life for some people, with benefits that may be durable.
• VNS isn’t for everyone. Clinicians consider treatment history, medical and psychiatric health, urgency, and goals when deciding whether someone is a good candidate for VNS.

If you’re researching vagus nerve stimulation for depression, you may be wondering whether it could finally help after years of treatments that haven’t provided enough relief. And if the idea of having a device implanted sounds like a big leap, you’re not alone.

VNS is a long-term therapy that works differently from medications and other depression treatments — but it’s not brain surgery, and it’s not an overnight solution. Also, “vagus nerve stimulation” can mean different things, from implanted devices to non-invasive stimulators.

To be clear, this article focuses primarily on implanted VNS. We’ll explain how implanted VNS works, who may be a candidate, what the evidence says, how long it can take to feel better, potential risks and side effects, insurance coverage, and how VNS compares with other types of depression treatments — so you can make a more informed decision about your options.

What is vagus nerve stimulation (VNS) for depression?

Vagus nerve stimulation (VNS) uses a surgically implanted device to deliver electrical pulses to the left cervical vagus nerve, stimulating brain regions involved in mood regulation, according to research in the Journal of the Neurological Sciences. Though VNS was first developed for drug-resistant epilepsy, the FDA approved adjunctive VNS for treatment-resistant depression in 2005, as mentioned in Brain Stimulation.

Often called the wandering nerve, “the vagus nerve is the body’s longest nerve, stretching from the brainstem down through the neck to our internal organs like the heart, lungs, and gut,” says Martijn Figee, MD, PhD, director of the Mount Sinai Interventional Psychiatry Program.

How does implanted VNS work?

Scientists don’t fully understand how VNS therapy for depression works yet, but here’s what we know so far:

• It changes brain activity: VNS affects mood-related brain regions, including the anterior insular cortex and prefrontal cortex, according to research in the Journal of the Neurological Sciences. Stimulating the vagus nerve in this way “is thought to help balance the brain and body interactions that are important for managing depression and stress, like reducing inflammation, boosting neurotransmitters, and making brain networks interact more flexibly,” explains Dr. Figee.

• Changes may come before symptom relief: Brain imaging suggests adaptive changes may occur within 3-6 months before antidepressant benefits become apparent, per research in Contemporary Clinical Trials.

Vagus nerve stimulation therapy isn’t brain surgery, but implantation does require a procedure under general anesthesia. A small battery-powered pulse generator (about the size of a silver dollar) is implanted under the skin below the left collarbone. It's connected to lead wires that wrap around the left cervical vagus nerve, according to research in Neuromodulation: Technology at the Neural Interface.

After surgery, you’ll typically have 2-3 weeks to heal before your provider activates the device. Once turned on, VNS delivers intermittent stimulation around the clock — sending signals for approximately 30 seconds every five minutes, per Dr. Figee – with settings adjusted as needed.

Some clinical trials suggest higher electrical charge may produce a more sustained response, although some people respond to much lower settings, per research in Contemporary Clinical Trials.

Who is VNS for?

The FDA indicates VNS for adults 18 and older with chronic or recurrent depression who are experiencing a major depressive episode and haven’t had an adequate response to four or more adequate antidepressant treatments.

But meeting those criteria is only the starting point. Clinicians also consider your medical and psychiatric history, previous treatment response, overall health, goals, and how urgently symptoms need to be addressed.

For example, VNS isn’t appropriate for people with current suicidal intent or an acute risk of self-harm because its antidepressant effects can take 3-12 months to emerge, according to research in Contemporary Clinical Trials. VNS also hasn’t been studied for psychotic disorders and may not be appropriate for depressed individuals who are also experiencing psychosis.

For people who are good candidates, VNS is a long-term treatment option that works alongside other treatments to improve depression management. “VNS stands out from other depression treatments because it can provide long-lasting relief for patients with severe depression who haven’t responded to therapy, medications, ketamine, TMS [transcranial magnetic stimulation], or ECT [electroconvulsive therapy],” says Dr. Figee. “It can also help with other symptoms like anxiety and fatigue, which might be linked to the vagus nerve’s role in stress and inflammation,” he adds. 

VNS is also considered when patients respond well to interventions like TMS or ECT but their symptoms rapidly return. VNS can help you stay well longer and helps prevent future episodes from being as severe.

Does vagus nerve stimulation work for depression?

VNS shows promise as an add-on treatment for depression, but patience is part of the package. In treatment-resistant depression, the “long-lasting effects of VNS can take a while to kick in, sometimes up to six months or more after the procedure,” says Dr. Figee. 

The landmark RECOVER trial illustrates why the results aren’t exactly black and white. Its prespecified primary outcome, a depression scale score, didn’t significantly distinguish VNS from sham treatment, according to research in the American Journal of Psychiatry. However, other measures of depressive symptoms, functioning, and quality of life favored active VNS.

The trial also found that benefits could persist: More than 80% of participants who had meaningful improvements at 12 months maintained them at 18 and 24 months. About 30% of those without meaningful benefits at 12 months improved during the second year.

Other large trials suggest some people may respond only after 9-12 months or longer, experience quality-of-life gains (even without meeting the standard definition of an antidepressant response), and sustain benefits for 10 years or more, per research in Contemporary Clinical Trials. Even though some people who received the VNS continued to report depression symptoms, they reported their quality of life was better since having the VNS device implanted.

What are the side effects and risks of VNS?

VNS is generally safe and well-tolerated, but like any treatment, it comes with some risks.

Common side effects (during the 30 seconds every five minutes that the device is active) include bradycardia (slow heart rate), hoarseness, cough, and nocturnal dyspnea (shortness of breath during sleep), according to research in European Journal of Neurology.

Rare surgical complications include hematoma, infection, and vocal cord palsy. One study — not specific to VNS for depression — puts the overall complication rate at around 2%, per research in the Journal of Neurosurgery. While uncommon, these risks are worth considering because VNS may require additional surgeries down the line (think: battery or lead replacements).

In other words, VNS can be a long-term commitment — not exactly a “set it and forget it” treatment. Talk with your provider about the potential benefits and risks so you can decide whether VNS makes sense for you.

How does VNS compare with TMS, ECT, Spravato, and ketamine?

VNS is a treatment option for depression that hasn't responded to four or more antidepressant treatments. Here’s how it compares with other commonly used treatments:

Transcranial magnetic stimulation (TMS): Magnetic pulses stimulate brain regions involved in mood.

• Invasive? No
• Anesthesia? No
• Initial burden? Standard TMS therapy typically involves 36 sessions over 4-6 weeks; accelerated protocols condense treatment into days or weeks
• How quickly? Some people improve within several sessions, while others take longer.
• Maintenance? Some people need maintenance sessions
• FDA status: FDA-cleared for treatment of major depressive disorder and anxious depression

Electroconvulsive therapy (ECT): Electrical currents intentionally trigger a brief seizure.

• Invasive? No, though an IV is placed
• Anesthesia? Yes
• Initial burden? Typically 6-12 treatments, two to three times weekly
• How quickly? Often rapidly, with improvement sometimes emerging after several treatments, as mentioned in Experimental and Therapeutic Medicine
• Maintenance? Some people need ongoing or maintenance ECT, per research in JAMA Psychiatry
• FDA status: FDA-cleared for treatment of catatonia, or severe depressive episodes associated with major depressive disorder, bipolar disorder, or treatment-resistant depression in patients 13 years and older

Ketamine: An anesthetic medication used off-label for depression

• Invasive? No, though an IV is usually placed for administration 
• Anesthesia? No
• Initial burden? Often 6-8 doses over the first few weeks
• How quickly? Some people improve after just a few treatments, according to research in Therapeutic Advances in Psychopharmacology
• Maintenance? Often needed
• FDA status: Not FDA-approved; used off-label only

Spravato (esketamine): A ketamine-derived nasal spray

• Invasive? No
• Initial burden? Typically administered twice weekly for four weeks, with each session lasting two hours or more
• How quickly? Some relief can occur within hours, according to research in Pharmacy and Therapeutics, but Spravato’s antidepressant effects typically build over several weeks.
• Maintenance? Often needed
• FDA status: FDA-approved for treatment-resistant depression and major depressive disorder with acute suicidal ideation

Is VNS for depression covered by insurance?

Sometimes, but FDA approval doesn’t guarantee coverage. “In the US, VNS is covered by several commercial insurance and Medicaid plans for treating depression that hasn’t responded to at least four different treatments,” says Dr. Figee. “Medicare, however, only covers VNS for bipolar depression in a clinical trial right now,” he adds.

Coverage varies by insurer and requires prior authorization and other requirements. If you’re considering VNS, check with your insurer and treatment team about coverage, pre-authorization requirements, and your potential out-of-pocket costs.

What about non-invasive vagus nerve stimulators like GammaCore?

Unlike traditional VNS, which requires an implanted device, non-invasive vagus nerve stimulation stimulates the vagus nerve through the skin, either at the neck or outer ear. Several vagus nerve stimulation devices use this approach. One example is GammaCore, a handheld stimulator FDA-approved for migraine and cluster headaches — not depression. It may be prescribed "off-label" for conditions influenced by vagal nerve stimulation, like depression, anxiety, and PTSD.

“A few studies have shown that non-invasive VNS, through an electrode clipped to the ear, can be effective for mild to moderate depression,” says Dr. Figee, adding, “but for more severe cases that don’t respond to other treatments, implanted VNS might be needed.”

The bottom line

VNS isn’t a fast fix or a one-size-fits-all solution. It’s a long-term option for people with difficult-to-treat depression, with benefits that may take time to emerge but can be durable.

A clinician can help determine whether VNS, Spravato, or another neuromodulation therapy (like TMS or ECT) best fits your diagnosis, urgency, treatment history, health, and preferences. If you’re considering VNS, you can explore depression treatments at Radial by connecting virtually or in person with a licensed clinician to see whether VNS is right for you.

Frequently asked questions (FAQs)

Can a VNS device be turned off or removed?

“The clinician can turn off the VNS using a programming tablet, or the patient can pause it by holding a magnet over their chest stimulator,” says Dr. Figee.

The device can also be safely removed or replaced, according to research in Acta Neurochirurgica.

Does VNS require battery replacement or ongoing maintenance?

Yep. “The VNS battery needs to be replaced surgically after about 7-10 years, depending on the stimulation settings,” says Dr. Figee.

Can VNS be used alongside medication, TMS, ECT, or other depression treatments?

“VNS can be safely used with medication, TMS, ECT, and any other antidepressant treatments, except for deep brain stimulation (DBS),” says Dr. Figee.

‍