The vagus nerve is a long nerve that does many things. It communicates with the brain about sensations in your gut. It conveys information about taste and speech from your mouth. And it affects the actions of smooth muscles that control the circulatory system, your breathing and your digestion. The word vagus comes from Latin, which means "wandering," and wander it does, passing from the brain stem through the neck and chest to the abdomen.
Scientists have long reported that electrical stimulation of the vagus nerve can reduce the rate of seizures in epilepsy. In 1997, the FDA approved this treatment, known as vagus nerve stimulation (VNS), for forms of epilepsy that get no better with drug treatment. In the summer of 2005, the FDA also approved VNS for treatment-resistant depression (TRD), which is defined as a long-lasting depression that has not improved even after four adequate trials of antidepressants.
Why Is This a Treatment for Depression?
Researchers started trying VNS for depression when they noticed that some patients being treated for epilepsy showed an improvement in mood, no matter how well the treatment worked for their seizures. In a way, this was not so surprising because anti-seizure medications have been helpful to some depression sufferers. VNS also appears to change the function of the nerve circuits and brain regions that are involved in depression.
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Does It Work?
The early studies of VNS for depression were open trials in patients with treatment-resistant depression. About one-third to one-half reported some benefit, and almost 30% were described as having completely recovered. For 90% of patients, whatever degree of improvement they achieved persisted. In contrast, more than half of patients treated with electroconvulsive therapy (ECT) relapse within a year.
In open trials, researchers are aware of the therapies that patients receive; treatments are not selected randomly, so valid comparisons of therapies cannot be made. Open trials are easily subject to bias, usually unintentional. So we need to temper our enthusiasm for benefits that appear quite impressive.
VNS is a unique procedure that requires surgery. So it is difficult to come up with a control or sham procedure that would allow for a randomized study. Also, a relatively small number of people are treated with VNS, so there are limited opportunities to study outcomes. Available studies have shown varied results. A few studies show no clear benefit, but some studies have shown small, but significant differences in favor of the VNS group. The study of VNS may also share the same problems we see with other depression treatments: It may be that it is quite helpful for a small subset of patients with depression, but it is difficult to predict in advance which people will benefit most.
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Getting the Treatment — What's Involved?
Since 1997, tens of thousands of patients have had the VNS device implanted (although these individuals have mostly been treated for disorders other than depression). A surgeon must wrap electrodes around the left vagus nerve as it passes through the neck and implant a pulse generator on the left side of the chest. The procedure takes an hour or so. The pulse generator is similar to a pacemaker — it is thin and light and about the size of a pocket watch. The generator is programmed by passing a wand over the chest wall. A stimulus is applied for about 30 seconds roughly every 5 minutes and the generator battery lasts 5 to 10 years.
In addition to the possible complications of surgery (post-operative pain and an infection rate of about 1%), patients can have symptoms associated with the stimulation. The cost of the equipment and procedure is $20,000 or more, which may or may not be covered by insurance. The most common effects are neck, throat, jaw and dental discomfort, as well as headache, hoarseness, alteration of the voice, cough and difficulty swallowing. These problems can be improved by reducing the intensity of the current. Researchers say that patients find the stimulation more tolerable as time passes.
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Is It a Treatment Worth Considering?
VNS does not appear to be a dramatically effective treatment for patients with treatment-resistant depression. But the research to date demonstrates that there is a small group of patients who may benefit.
Anyone considering VNS treatment should be aware of its limitations. VNS has not been proven useful in the acute phase of depression. The merits of long-term treatment also have yet to be confirmed effective by rigorous, randomized, controlled trials.
VNS should be used only when a person has not responded to several other types of treatment for depression. The person must fully understand the pros and cons because this form of therapy requires a commitment to have surgery and to use the device for at least one year. It takes that long to assess how useful this therapy has been. If no improvement in symptoms of depression is seen after 12 months of use, it is unlikely that continued use will lead to a better result.
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The Bottom Line
It is always useful to have a novel treatment available for patients with the toughest forms of depression. But we need more research to determine which patients are most likely to benefit from this relatively less researched and costly treatment.
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Michael Craig Miller, M.D., is the editor in chief of the Harvard Mental Health Letter. He is also associate physician at Beth Israel Deaconess Medical Center and assistant professor at Harvard Medical School. He has been practicing psychiatry for over 25 years at Beth Israel Deaconess Medical Center. He is an active teacher in the Harvard Longwood Psychiatry Residency Program.