[SymphonicHealth] F.D.A. Considers Implant Device for Depression (fwd)

[Guest guest]

Damn, the allopaths are at it again!

Talk about WIRING up people!

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May 21, 2005

F.D.A. Considers Implant Device for DepressionBy BENEDICT CAREY

The Food and Drug Administration may soon approve a medical device that would be

the first new treatment option for severely depressed patients in a generation,

despite the misgivings of many experts who say there is little evidence that it

works.

The pacemaker-like device, called a vagus nerve stimulator, is surgically

implanted in the upper chest, and its wires are threaded into the neck, where it

stimulates a nerve leading to the brain. It has been approved since 1997 for the

treatment of some epilepsy patients, and the drug agency has told the

manufacturer that it is now " approvable " for severe depression that is resistant

to other treatment.

But in the only rigorously controlled trial so far in depressed patients, the

stimulator was no more effective than surgery in which it was implanted but not

turned on.

While some patients show significantly improved moods after having the $15,000

device implanted, most do not, the study found. And once the device is

implanted, it is hard to remove entirely; surgeons say the wire leads are

usually left inside the neck.

Proponents say that many severely depressed patients do not respond to

antidepressants or electroshock therapy and that those patients are desperate

for any treatment to relieve their suffering.

" These people have no other options, so we need to consider anything that shows

potential to help, " said Dr. Harold A. Sackeim, chief of biological psychiatry

at the New York State Psychiatric Institute, who consults for Cyberonics Inc.,

the Houston company that makes the stimulator.

But Dr. Thase, a psychiatrist at the University of Pittsburgh who

consults for the company, said there was " simply not a good enough basis in

evidence " for approval. While the device is promising, Dr. Thase said, " the

shaky state of the evidence means we have to be very cautious with this and

prepare for the possibility that the hoped-for benefit isn't there. "

The drug agency has given mixed signals about the stimulator. In August 2004, it

told Cyberonics in a letter that the treatment was not approvable, saying more

information was needed. But in February, after the company provided more data,

the agency changed that position, informing the company that the stimulator

could now be approved. The company's stock price has fluctuated as investors try

to anticipate the agency's decision, which the company is hopeful will come by

the end of the month.

The Senate Finance Committee recently began looking into the F.D.A.'s potential

reversal, but Cyberonics officials say they have been assured by the agency that

this will have no bearing on its final decision.

In a conference call with reporters and analysts on Thursday, Cummins,

the company's chief executive, said no other treatment had been deemed

approvable by the drug agency for stubbornly depressed patients. Clearly, he

said, " the status quo for millions of Americans, their families, psychiatrists

and payers is neither safe nor effective. "

Still, some patient advocates and other experts are now questioning how the

device has come so close to approval with such limited evidence for its

effectiveness.

" I've never seen anything quite like this, " said Dr. Lurie, deputy

director of health research at Public Citizen, a nonprofit group that is a

frequent critic of the F.D.A. and the drug and medical-device industries. " What

we could be setting ourselves up for is an epidemic of implantation of a device

with no proven effectiveness. "

Experts who were involved in the approval process say they were moved by the

desperate prognosis for severe depression and by powerful testimonials.

At a critical meeting of an F.D.A. panel last June, six patients with chronic

severe depression said they felt much better that the stimulator had been

implanted, as part of an investigational study. At that meeting, the panel voted

5 to 2 to recommend that the device be approved.

One patient, Donovan III of St. Louis, said the stimulator had saved his

life. " I went from being a complete mental-health vegetable to someone who had

the energy and confidence to do this book, " Mr. Donovan said in an interview.

But the panel did not hear from patients who did not benefit from the

stimulator, according to the transcripts. One of them, Coram, 57, of

Silver Spring, Md., signed up for the trial after seeing a newspaper

advertisement about it.

" Believe me, when you're depressed for long enough, you get to a stage where

you're willing to try almost anything, " Ms. Coram said in an interview.

In the study, doctors implanted the device in 235 severely depressed people. The

stimulator sends timed pulses of electricity to the vagus nerve, which has wide

connections throughout the brain.

Half of the patients then had their stimulators turned on. The investigators did

not know which of their patients had their stimulators on.

After three months, researchers " unblinded " the study and compared levels of

depression in the two groups based on standard measures of disease severity, the

F.D.A. documents show. They found that 17 of the 111 patients who had implants

turned on and completed the trial showed significant improvement. But 11 of 110

who had no stimulation and completed the trial also felt significantly better.

The difference between the two groups was small enough to be attributable to

chance.

Alan Totah, vice president of regulatory affairs for Cyberonics, said at the

meeting, " The primary endpoint did not reach statistical significance. " But Mr.

Totah said " the results did show a positive trend in favor " of the stimulator.

Hoarseness was a common complaint. Many patients who have had a stimulator on

also said that it put a quiver, rumble or other odd inflection in their voices.

" I certainly knew mine was on, " Ms. Coram said. " I could feel it. You get this

constricting pain in the back of the throat. I couldn't talk sometimes. "

Ms. Coram said that she was slightly more functional at work after the surgery

but that it did not last. Later, she said, after she took a doctor's advice and

had the stimulator's pulse turned up higher, " my life fell apart. "

" I was very anxious and agitated, much more so than before, " she went on. " I

felt suicidal for a while, worse than I had been in 8 to 10 years. "

But several members of the panel that voted for approval said that given the

alternatives for people like Mr. Donovan and others who did well, the

insignificant difference between the two groups was cast in a different light.

" The feeling was that anything that gives these people hope is potentially

worthwhile, " the chairwoman, Dr. Kyra Becker, a neurologist at the University of

Washington, said in an interview. " But the whole meeting was uncomfortable, and

everyone wanted to see another trial done, no question about it. "

Dr. Becker said that if she had voted her conscience, solely on the basis of the

evidence, she would have voted not to approve.

A member who voted against approval, Dr. Malone, a psychiatrist at

Drexel University College of Medicine in Philadelphia, said he was bewildered by

the recommendation.

" I walked out of there thinking I was nuts, " Dr. Malone said in an interview.

" It was stunning, but then I find much of life is stunning. "

The F.D.A. usually follows the recommendations of advisory panels.

Another reason some psychiatrists are intrigued by the device for depression is

a finding in the evidence that some people with the implant might do better over

time. In follow-up data, Cyberonics reported to the drug agency that about 30

percent of those in the study showed significant improvement on one measure of

depression after six months or more.

" The effect appears to be sustained, which is very significant in these

patients, who almost always relapse, " Dr. Sackeim said.

But other experts say it is extremely difficult to interpret this long-term

evidence. Many patients in the study were taking psychiatric medications, or had

electroconvulsive therapy, both of which can improve mood. These and other

factors are difficult to control for, despite the company's efforts to do so,

they said.

Cyberonics says that the long-term evidence it has provided to the federal

agency satisfies requirements for approval, and that senior agency officials

have told the company as much.

The agency has a higher standard of proof for approving new drugs than it does

for devices. Devices require a " reasonable assurance " that they are safe and

effective and that potential benefit outweighs the risk.

F.D.A. officials said they could not comment on any product that was pending

approval. But Dr. Donna-Bea Tillman, director of the agency's office of device

evaluation, said " it is not the kiss of death " if a product's effectiveness is

not supported by a well-controlled clinical trial.

" We consider safety and effectiveness in relation to the alternatives that

patient population has, including whether they have any alternatives at all, "

Dr. Tillman said.

If a device is approved, the agency specifies precisely which patients should

have access to it, she said. Whether to recommend it is then left to doctors'

judgment.

And that is a prime concern among critics of the approval process, like Public

Citizen and other groups concerned about patient protection. Once a product has

been approved, the manufacturer can promote it aggressively, and some doctors

may recommend it to any patient, whether severely or moderately depressed.

Some people may not wait for approval. Sue Wanemaker, 51, who lives near Denver,

said she had a vagus stimulator implanted last April for her depression. Ms.

Wanemaker, who also has epilepsy, said she had noticed little benefit, and added

that when turned up high the stimulation made her feel suicidal.

She has since had the device turned down. " I'm going to hang in there, " she said

in a phone interview, " because why not, I've got it in now, and - there it

goes! " With that, her voice trilled for a few moments.