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What's on the Horizon for Refractory Depression Therapy?
by Susan Weiss, Ph.D., senior director, Research, NMHA

Although depression is a common and treatable form of mental illness, some people suffer from a form of severe and chronic depression that fails to respond to conventional treatment and medication. These people have "refractory depression," which is estimated to affect between 10 and 15 percent of people with unipolar or bipolar depression. 

One promising technique now offers hope to those with refractory depression. It involves the use of an implanted device called a vagus nerve stimulator (VNS), which is already used to treat severe epilepsy and now shows promise for depression treatment. The device, which is about the size of a pocket watch, is implanted under the skin in the upper chest region, and functions similarly to a cardiac pacemaker. It sends electrical signals to the vagus nerve, which communicates to the brain's wide-reaching neural networks. 

VNS development began in 1985 when animal research demonstrated that vagus nerve stimulation could inhibit seizures. Since the Food and Drug Administration's 1997 approval of VNS for refractory epilepsy, more than 9,000 people worldwide have been fitted with the device. 

Psychiatrists first noticed VNS as a potential depression therapy when some people using the device for epilepsy reported a substantial improvement in their moods—whether or not their seizures were reduced. The reasons why treatment for epilepsy and mood disorders overlap are unclear, but the brain areas involved in emotion and memory are also the most vulnerable to disruption by epilepsy. In fact, many mood stabilizers used for bipolar illness are also anticonvulsants that were originally developed to treat epilepsy. 

A recent clinical trial involving 30 patients with refractory depression shows that 40 percent showed marked improvement with VNS treatment. Among the most encouraging study results are the device's persistent antidepressant effect over time and, in many cases, an increased therapeutic benefit with long-term use (note that study participants took medication along with the VNS treatment). 

VNS has surprisingly few side effects—the most commonly reported problem is hoarseness. Some people with epilepsy have experienced side effects that required the device's removal, but no long-term effects have been reported. In addition, VNS patients can use a magnetic device to shut off the stimulator at any time by placing it over the VNS implant in their chest area, or the stimulator can be removed permanently, if necessary.             

Using VNS as a treatment for depression remains experimental but is being tested in a clinical trial designed to meet FDA standards for approval. Canada has already approved VNS for use in depression. 

Vagal nerve stimulation may be the first of a variety of approaches used to treat people with severe mental illnesses who do not respond to available therapies. And for people with treatment-refractory depression, these new possibilities bring hope for a better life. 

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