In a letter sent to the manufacturer, Cyberonics Inc., the FDA says that without additional information, the device is "not approvable." Cyberonics is a WebMD sponsor.
In June, the FDA's advisory committee on neurological devices recommended approval of the device, called a vagus nerve stimulation (VNS) system, in a 5-2 decision. But several committee members at the meeting said they weren't convinced that the device was effective.
VNS consists of a stopwatch-sized device that's surgically implanted in the upper chest. Tiny wires attach the device to the vagus nerve, which runs from the neck to the brain and is thought to stimulate areas of the brain involved in regulating mood.
The device is programmed to send electrical impulses to the vagus nerve every few seconds, thereby stimulating the brain in an effort to treat depression. The company says the device is intended only for adults with severe depression who have not responded to treatment with antidepressant drugs.
Depression Device Rejected
The device has been used since 1997 to treat patients with treatment-resistant epilepsy. Since then, the company says more than 22,000 patients have received the implanted device, called vagus nerve stimulation (VNS).
Data submitted by Cyberonics at the advisory committee meeting in June showed little improvement in depression symptoms after patients used the device for three months. But company officials point to data showing that 18 of 59 patients showed at least a 50% improvement in depression after one year of use. Twenty-five out of the 59 showed improvements after two years.
Officials argue that the improvements are especially beneficial since many severely depressed patients fail to reliably take medication and often do not show long-term improvements with antidepressant drugs.
"I think there are certainly hints to efficacy. I think it's not been proved," said Kyra J. Becker, MD, a neurologist at the University of Washington School of Medicine in Seattle and chairwoman of the FDA panel, at the meeting.
In addition, some experts expressed concerns that the company had not done enough to show that VNS was responsible for the improvements in depression symptoms. Many patients in the trial knew that they were receiving VNS stimulation, making them vulnerable to a placebo effect. Patients in the studies were also allowed to take antidepressant drugs and other medications, which could have skewed the results, they say.
Committee members also raised questions about the safety of the device. Up to two-thirds of patients using VNS for depression or epilepsy experience alterations in their voice because of the electrical pulses to the vagus nerve. Many patients also experience mild side effects including persistent cough.
Patients can deactivate the device with a magnet if they become uncomfortable or want to alleviate the voice alterations.
About 1% of patients using the device for epilepsy have to have it removed due to infection, according to the company.
But the experts were more concerned about suggestions that the implants may carry risks for some patients. In one study, 31 of 235 patients had episodes of deepening depression, and many had two or more episodes of worsening depression, according to the company.
Twenty-five patients using VNS also attempted suicide in several company studies. The experts acknowledge that suicide is a common risk in severely depressed patients but say they are still worried about the product's safety.
Cyberonics officials say they were "shocked" by the FDA's decision and are in the process of arranging a meeting with the FDA to discuss their letter and address their concerns.
With reporting by Todd Zwillich.