A technique that uses a device similar to a pacemaker to reduce depression has significant benefits that remain undiminished for at least two years.
That is the result of a follow-up study reported on Sunday by Mark George of the Medical University of South Carolina and on Monday by his collaborator, A. John Rush of the University of Texas Southwestern Medical Center in Dallas, Texas at the annual meeting of the American College of Neuropsychopharmacology held in Waikoloa, Hawaii.
The technique is called vagus nerve stimulation, or VNS. It involves implanting an electronic device in the chest and connecting it to the left vagus nerve in the neck. The device sends intermittent signals to the nerve, which carries them to the brain. The vagus nerve is a major nerve that carries sensory information to the brain from the heart and other internal organs.
VNS was developed by Cyberonics, Inc. of Houston, Texas to treat epilepsy. The device was invented by Dr. Jake Zabara.
While attending a Lamaze class with his wife, Zabara began wondering how controlled breathing could affect pain levels. Exploring this connection led him to the vagus nerve.
When animal studies showed that electrical stimulation of the vagus nerve could stop epileptic seizures, he founded Cyberonics, which developed the VNS device. It was approved for treatment of severe epilepsy in Europe in 1994 and in the U.S. in 1997, and now has been implanted in more than 14,000 epilepsy patients worldwide.
Because of anecdotal evidence that the device has a positive side effect on improving patients' moods and the fact that it connects to the brain in areas known to regulate mood, Cyberonics commissioned a pilot study to assess the device's effectiveness in treating depression.
The study was conducted by a team of researchers including Rush, George, Harold Sackeim at Columbia University and Lauren Marangell at Baylor College of Medicine. The researchers recruited 30 adults who exhibited both bipolar and unipolar forms of severe depression and had failed to respond to at least two medications. After positive initial results, they added another 30 people to the study a year later.
"In the eight weeks after VNS treatment had been added to their existing medication, 30 to 40 percent reported some improvement," said George, "but what really made us sit up and take notice was the fact that the symptoms completely vanished in about 20 percent of the patients. I've been treating these kinds of patients for more than a decade and I've never seen anything like it."
The technique worked best with those who had failed two or three medications: Sixty percent showed improvement. However, none of the most treatment-resistant -- those who had failed eight or more medications -- showed any benefit, the researchers report.
The study was conducted without a control group so the researchers could not rule out the possibility that some of the positive effects might have been due either to the surgery or to a placebo effect. There was also the question of tolerance. A major problem with antidepressant drugs is that over time, they lose their efficacy with some individuals.
"We really don't know the cause of tolerance in these drugs, so we were worried about the possibility of a 'Flowers for Algernon' effect, that the improvements would prove too temporary," said George.
So the researchers conducted a two-year follow-up study with the patients in the pilot study.
"The results of the follow-up study not only indicate that those who responded initially to VNS therapy continued to stay well, but also that some of the subjects who did not respond initially improved later on," Rush said.
"There has been no evidence of a tolerance effect. If anything, patients have continued to improve. Several, acting against the advice of their doctors, have even stopped taking antidepressant drugs and seem to be doing quite well," the researchers report.
VNS is still considered an experimental treatment for depression in the United States, but the results of the pilot study were enough to get it approved as a treatment for depression in Europe and Canada. Cyberonics is currently conducting a double-blind clinical trial of the effectiveness of VNS for treating depression; the results should be announced in the spring.
The study was funded by Cyberonics, Inc. George and Rush state that they do not have any financial stake in the company and its products beyond serving as paid consultants.
The American College of Neuropsychopharmacology (ACNP), founded in 1961, is a professional organization of some 600 leading scientists. Members are selected primarily on the basis of their original research contributions to the field of neuropsychopharmacology, which involves the evaluation of the effects of natural and synthetic compounds upon the brain, mind and human behavior.
The principal functions of the College are research and education. ACNP's annual meeting is limited to participants from around the world who have made major research or clinical contributions in the field.
[Contact: Dr. Oakley Ray, Mark George, A. John Rush, Kathy Latimer]