As reported by The Hartford Courant, July 6, 2006.

A Last Resort

New Method Offers Hope for the Treatment-Resistant

By Jesse Leavenworth

Many people with severe depression have watched their hopes wither again and again.

"I've seen patients who have been on literally every known antidepressant on the market and whose lives are still being devastated," said Dr. Andrew Winokur, a psychiatrist and director of psychopharmacology at the University of Connecticut Health Center. "We have an obligation to find anything else that can legitimately work for those people."

The health center recently began offering a new and still-controversial remedy for patients with so-called treatment-resistant depression. Vagus (pronounced like "Vegas") nerve stimulation, or VNS, uses a device surgically implanted in the patient's chest, with wires attached to the left vagus nerve in the neck.

Similar to a pacemaker for the heart, the pocketwatch-size device sends an adjustable electrical impulse to the nerve, which is connected to parts of the brain involved with mood and emotion. The constant impulses are supposed to stimulate production of beneficial brain chemicals, including the neurotransmitter serotonin.

The U.S. Food and Drug Administration approved VNS last year as a treatment for people 18 and older who have not responded to at least four other courses of treatment.

"The important thing to recognize, to put this in context, is that VNS is for a sub-population of individuals for whom there are not good options presently," Dr. Leighton Huey, head of the health center's psychiatry department, wrote in an e-mail.

Of the approximately 18.8 million Americans suffering from depression, 20 percent to 25 percent have not responded to other depression treatments, and many of them remain prime candidates for suicide.

UConn is the main center in the state performing VNS implants and evaluations, said Huey. The health center has implanted four patients with the VNS device, and at least three others are awaiting the procedure.

"We have a group of academic psychiatrists who specialize in mood disorders, so this is a natural extension of that expertise," Huey wrote.

Joan, who asked that her real name not be used, received her implant in April and says she already feels better. Now 54, Joan has suffered from depression since 1974 and had tried 44 different types of medications and still had suicidal feelings. But lately she's been feeling more hopeful. "For the last few weeks, I've not been suicidal," she said.

She says the tone of her voice has changed from low monotone to upbeat. "I feel more optimistic and happy," she said. "My sense of humor came back."

The health center is part of a national 5-year-long effort tracking 1,000 people with treatment-resistant depression who have had the VNS device implanted and 1,000 others, also with severe depression, who do not have the device, Huey wrote.

At the health center, VNS will be used in tandem with other treatments, including medication and electroconvulsive therapy, Leighton wrote. Both he and Winokur said they are heartened by recent studies that show VNS is effective for a significant portion of people with treatment-resistant depression.

"The more recent data are suggesting that response is being seen earlier than the first studies, sometimes in the first three months," Huey wrote.

However, other psychiatrists and scientists have not been convinced. The FDA approval last July came over the objections of 20 agency staff members who said the procedure's effectiveness had not been proven.

"Pancreatic cancer is a hopeless condition" with a much higher death rate than chronic depression, said Philadelphia psychiatrist Richard P. Malone, a member of the panel that voted against approval. "And we have as much evidence that this works for pancreatic cancer as it does for depression. Why not use it for that?"

Also, a majority of insurance companies have found insufficient evidence that the device works and have refused to pay for the procedure. A report by Harvard Pilgrim Health Care, an influential mental-health insurer in Boston, called VNS "experimental, investigational and unproven." The device costs about $12,000, and the surgery bill can approach $15,000.

But Winokur said studies have shown that positive response to VNS improves over time. In a recent issue of the journal "Psychiatry," three physicians from the VNS Clinic at the University of Pennsylvania call the nerve stimulator "an important new addition" to available treatments for severe depression. The authors cited a study that showed VNS, used with medication and other treatments, was two to three times more effective than those other treatments alone. They acknowledged that a higher proven effectiveness, particularly for a treatment involving surgery, would be desirable.

"However, this is unfortunately a nave and unrealistic expectation in the setting of severe [treatment-resistant depression]," Drs. John O'Reardon, Pilar Cristancho and Andrew Peshek wrote, "analogous to expecting a newly adopted chemotherapy to deliver remission rates in excess of 50 percent in patients with advanced cancer."

Also, some patients who do not respond to medication have refused to undergo electroconvulsive therapy, or ECT. Although the treatment has advanced greatly since the treatment's depiction in the movie "One Flew Over the Cuckoo's Nest," so-called shock therapy still carries a stigma of shame and the risk of dangerous side effects.

"When patient reluctance to undergo ECT due to stigma is combined with some legitimate concerns regarding adverse effects of ECT on memory function, it means that our most effective treatment for severe depression is and will likely continue to be a much underutilized one," the physician authors wrote in "Psychiatry."

After outlining the available depression treatments and the limitations of each, they wrote, "Given all of the above, there is a clear need for additional treatment options for the severely depressed patient group."

So far, only a handful of patients at the UConn Health Center have had the VNS device implanted since January, Winokur said. The main side effect has been hoarseness, but people with the implant can use a small magnet to turn off the device when, for example, they have to make a public speech, he said.