A Jolt to the System

Tony Abdo aabdo at SPAMwebtv.net
Wed Mar 28 11:36:37 MST 2001


Speaking of frankenstein ag and frankenstein medicine...  meet Dr. John
Rush and Houston firm, Cyberonics.

Tony
___________________________
A Jolt to the System

This small electrical device may be the last hope for the chronically
depressed
By Lisa Singh

Everything was dark. Her eyes. Her clothes. The very core of her being.
The psychiatrist asked how she felt.

"That's the thing," said Lauri Sandoval, scrunching her face. "I don't
feel."

That numbness. Sandoval knew its source: the depression that had been
her life's shadow and had led to two suicide attempts, one at 20 when
she downed pills from her mother's medicine cabinet and slit her wrists,
the other in 1995 when she swallowed some tranquilizers with alcohol.

Now, her accomplishments, being a ballet dancer for 15 years, and later,
an assistant to former Secretary of State James Baker, didn't matter.
Her illness had dragged her down; her focus was shot, her fatigue heavy,
and she had ballooned to a size 18, all because a common
anti-depressant, Remeron, had fueled her appetite but done nothing to
quash her illness. As for her two-year job as Baker's assistant, it
ended badly. On one of his world missions, she put him on the wrong
flight. He was kind about the misstep and simply said that mistakes like
that couldn't happen. But she cried inconsolably in his presence. She
still had a job, but she was slipping into a place so dark she didn't
know if she could emerge.

Soon, she quit her job and found the only work of which she was capable:
cleaning dog cages and people's homes.

"I'm real tired," she said to Dr. Lauren Marangell of Houston's Baylor
College of Medicine. "Life's a job. I just wonder if it'll ever be easy.

"Maybe," she continued, "if this device works for me and other people,
it would be like being given a gift."

She was speaking of an experimental treatment, a mere 3-ounce device
placed in the chest beneath the skin. The size of a small pocket watch,
it sends electrical impulses to a crucial nerve in the neck.

The vagus nerve, as it's called, is an information superhighway that
goes to parts of the brain that control emotion, sleep, appetite, the
very things that can be affected by depression. For a decade, the vagus
nerve stimulation (VNS) device had been used to treat epilepsy, a
condition for which the Food and Drug Administration approved its use in
1997.

Along the way, scientists also noticed a curious side effect, that it
lifted some patients' moods. The next step was to try it on those
suffering from treatment-resistant depression, some of the one million
people nationwide for whom a slew of medications, therapy, and, in some
cases, electroconvulsive therapy, hadn't worked.

Sandoval was ready, hoping that the device could bring her the lasting
peace that anti-depressants hadn't. "I'd love to feel joy," she said,
tearing up. "Just to be able to feel that."

"You know that this is experimental," said her doctor of the device that
some see as a brain pacemaker, a way to regulate mood as a mechanism
might similarly manage the heart. "We don't know if it'll work or not."

Sandoval nodded. "It might work," she said, "but if it doesn't, I won't
be worse off...knock on wood." She let out a nervous laugh.

"There's no wood here," Marangell said.
It's been about two years since Sandoval and 29 other people, about half
from the Dallas area, joined doctors trying to answer one of the most
pressing questions facing the world of psychiatry: Could the VNS device
be a last-ditch hope for the chronically depressed and succeed when all
other therapies had failed? There were four hospitals in the study, in
New York, South Carolina, Houston, and at Dallas' University of Texas
Southwestern Medical Center. That initial trial offered encouraging
results; after 10 weeks, 40 percent of the patients showed a significant
improvement in mood. Of that number, about 17 percent even said their
depression was now totally gone.

Of the remaining 60 percent who saw no improvement, only two became
worse, but that, as Southwestern's Dr. John Rush says, is only because
of the nature of depression itself. "It waxes and wanes," he says,
adding that no one attempted suicide or has since.

Of the success rate, Rush, who was chosen by the device's manufacturer,
Cyberonics, to lead both studies, says: "We would have been excited if
we would have gotten anything over 10 percent. It was surprising."

Now, doctors are seeking to determine if those results were merely a
fluke or if they can be replicated. A second, larger trial, this time a
controlled, double-blind study, is under way. About 210 patients, at
both UT Southwestern and 19 other medical sites, are receiving implants,
and as before, Rush is leading the entire study. "To my knowledge, it's
the only device currently under investigation," he says, "and it's the
only device that is being developed for depression. So it's pretty
cutting-edge."

In the current study, half of all the patients' devices will be
activated for 10 weeks while the remainder stays off. At a later point,
the second group will have its devices activated, but the patients won't
know when. "We're certainly very excited," says Dr. Mustafa Husain, a
lead investigator of the trial at UT Southwestern, "but we want to
approach it in an objective way. Our main interest is the safety of the
patient."

Patients in the pilot study had commonly gone from one anti-depressant
to another with fleeting or no improvement in mood. About half had even
tried electroconvulsive therapy--popularly known as shock therapy. Of
what results VNS may bring, Rush says, "Our impression so far is that it
at least holds over time. It may increase a little bit."

As with the first study, the second trial is funded by Cyberonics, a
Houston-based company founded in 1987 that developed and holds a patent
on the $15,000 VNS implant and markets it and other medical devices
primarily for the treatment of epilepsy and other neurological
disorders.
Results should be known by 2002, with possible FDA approval to follow.

For Sandoval, six months after the device was implanted, she felt a
definite change.
One day, she came to Marangell's office looking like a new person. She'd
lost more than 50 pounds and wore, for the first time in many months,
light-colored clothes.

"It's changed my whole life," Sandoval said, smiling and sounding as if
she were in an infomercial.

"Let me play devil's advocate for a minute," Marangell said. "How do we
know that it's not by chance that you're feeling better?"

"Because in my 41 years, the normal pattern has been that I might feel
better for a few weeks, a few months, then I'd slip back into
depression. Now, there are no signs," Sandoval said.

"Any thoughts of death?"
She shook her head. No.
Sandoval said she'd become more productive. Having moved to Santa Fe to
live with her mother, she was now working at an antique shop. "I have
energy. I can be with people. It's totally different."

Was she happy? Marangell asked at another point.

"It's not happy," Sandoval said. "It's content. I don't feel sad
anymore. I feel everything is going to be OK."

Sandoval now says that like her mother and grandmother, she suffers from
a hereditary condition. She came from a stable family; her mother was a
teacher, her father was an environmental engineer, and the family lived
on a Nevada farm. But early on, Sandoval showed signs of depression. She
was withdrawn, a poor student. On weekends, she often sat in a rocking
chair for hours, swaying in silence. Her family never understood her
dark moods, and she later came to welcome the physical illnesses that
befell her: her three bouts with cancer, the sarcoidosis that robbed her
of 30 percent of her lung. It was easier at those times to get
compassion from people. Of her depression, her family often told her:
"Go for a walk. You'll feel better." Or, "What do you have to complain
about?"

Sandoval recovered from the cancers and the lung ailment, but the
depression stayed. The only thing that has helped pull her back from the
brink is the contraption lodged in her chest. Doctors, however, don't
know what the long-term effects of VNS might be. It could, for instance,
lead to paralysis of the vagus nerve or the growth of a tumor. Sandoval
doesn't dwell on such possibilities. "I can have a life without the
depression," she says now, speaking by phone from Santa Fe.

Throughout the hour's conversation, she occasionally laughs heartily and
says that last year, she wrote a Christmas letter to all of her friends
and family, telling them about VNS. As if in some rags-to-riches tale,
she has even landed a job as an assistant to a movie star in Santa Fe,
where she oversees his 6,000-acre ranch.
Sandoval says she'll carry that device for the rest of her life. Her
only fear: If the FDA eventually approves it, she'll have to assume the
financial responsibility for its upkeep, which includes changing the
battery. Typically, the device stimulates the vagus nerve at timed
intervals, every hour of the day, seven days a week, until the battery
runs out anywhere from three to five years later.

Cyberonics continues to pay for Sandoval's trips to Houston every three
months for her checkup. "I don't know what I would do if I couldn't get
another battery," Sandoval says, then adds with a laugh, "Doesn't that
sound weird?"

If someone told Jimmie Carson that taking a hatchet knife to her hand
would end her mental pain, she'd do it. When she tells you this, you
believe her. There's something about the way she says it, how she
manages eye contact, if only briefly. Most of the time, she has to force
herself to focus, all because she lives in a drugged state, her body
pumped with four different anti-depressants and Ritalin to boot.

In her Grapevine home, this 57-year-old woman stumbles before an easy
chair, before finally managing to take a seat. Those pills, she says,
confound her equilibrium. That would be a small price to pay if only
they'd work. These days, their way of ending her illness--she thinks it
began in 1974 when she spiraled into pospartum depression following
childbirth--is to numb her. "It hasn't stopped my depression," she says,
"but made it livable...at least I don't spend time thinking how to kill
myself."

More than a year ago, she had the VNS device implanted. She wishes she
could say it's helped her depression, but all she can offer is a slim
maybe. She says it probably has helped rid her of something else: the
panic attacks that she says are worse than depression itself.

And for that single reason, she says of the device: "I'll never let them
take it out."
She still worries, knows that she's becoming less independent, that one
day her depression will win. Before its onslaught, she could handle
life, the management of the businesses, the bowling alley, the casinos
both here and abroad that she and her husband owned.

That tough-minded person she once was, "that person is still inside,"
she says, her eyes teary, "but I can't do the things I used to." Each
day, she sets a goal for herself. Today's: Vacuum before the reporter
comes. Now divorced, living alone in a three-bedroom home, everything
around her seems in place; antiques and intricate decor fill her home.

The place seems tidy, but she says that's only because she barely moves.
She knows, too. "It's dirty," she says, frowning. She often sits on the
large easy chair, her television tuned to the TV Guide channel. By the
time she's finished scrolling the list of programs, she's already
forgotten what she's decided to watch, so the television remains on that
station all day. That's her problem, she says: "CRS--Can't Remember
Shit." She'll often lounge around for days on end in a nightgown. Today,
though, she has managed to don makeup and a velvet shirt and pants. If
she leaves her home, which is rare, it is to see her doctor, the one who
recommended her for the VNS study.

Why some patients have responded better to VNS than others, no one can
say for sure. "I can give you speculation," Rush says. "Depression
probably has different biologies and a lot of different genetics, so
it's not just one illness. We don't have one treatment that works for
everybody."

For a man who's regarded as one of America's leading depression
investigators, it's the closest he or anyone can come to a definitive
answer.
Rush had once thought he'd be a mathematician, until the day, as a
Princeton undergraduate, he was confronted with a problem he couldn't
solve. When another classmate beat him to it, he knew that it was time
to switch his major.

For the past three decades, Rush, an affable, unassuming man of 58, has
tried answering a larger, vexing equation: the mystery of mental
illness' roots.
But in all his years in psychiatry, he's never encountered what he did
nearly two years ago, when he met the patients in the VNS pilot study.
"They were the most poorly functioning set of outpatients with
depression I've ever seen," he says. "This is not the happy-go-lucky
characters that go to a psychotherapist to complain about their
problems. They've been to hell and back with the treatments, and they're
not well." Many couldn't hold down jobs. All were referred to the study
by psychiatrists who'd exhausted all of their options.

When Rush began his career, there were only a handful of drugs, as well
as psychotherapy and electroconvulsive therapy, available to patients.
Now, the whole of neuroscience is massively different than it was even
10 years ago, as it's grown to include knowledge of neurotransmitters.
Rush postulates that the VNS device may affect the production and
activity of the neurotransmitter in the brain that is linked to
depression. Studies so far have shown that VNS can change blood flow to
certain parts of the brain that are known to be related to the illness.

The VNS surgery takes about two hours, and for about eight weeks, the
electrical current stays the same. It is adjusted, if necessary, based
on the patient's response. Once the device is set, the charge
determined, it goes for years, until the battery runs out. To date, only
one person in the pilot study has had the device removed, and the
remainder continue to check in with doctors involved in the trial.

As for improvements, Rush has seen a range of responses. Some didn't see
results for weeks. For others, it took several months. "It varies from
person to person. Sometimes a person will say I feel less anxious. Or
I'm concentrating better...but what you see is these symptoms of
depression gradually get less and less severe."

Joanne Tesoriero was one who saw results.

"I felt it was a gift from God, my last hope, really," says Tesoriero, a
52-year-old mother of seven who was the last person accepted into the
30-patient pilot program. Someone had dropped out, which was the only
reason she was admitted. Her psychiatrist had been to a conference where
Rush was speaking about VNS, and was "100 percent for it."

"And so was my husband," Tesoriero adds. "It's hard on the family.
Because you don't take pleasure in the things you used to. Can't
connect." Not with her pets. Not with her children.

These days, she's added five more kittens to her home. "They're lovable,
they're huggable. You feel a lot when you hold them," she says, smiling
broadly.
Before VNS, Tesoriero's depression, which she attributes to postpartum
depression, got so severe that she stopped eating. "I just left it in
God's hands," says this devout Catholic, whose home is filled with
Christian relics, such as the cross hanging over her kitchen door. At
her worst, she had said, "Take me, Lord. If you want to save me, save
me, but I'm not going to do anything to survive."

As her weight dropped, she was hospitalized for three weeks. During that
time, she was given six electroconvulsive therapy sessions, which
helped. But "it felt like something from the Middle Ages. Just the
thought of it," she says. And it affected her memory. VNS, in contrast
to electroconvulsive therapy, delivers small charges of electricity over
years of time. The amount of electricity is less than the charge of a
single battery one would put in a flashlight. "A trivial amount of
electricity," Rush says. "You can't feel it."

"I don't mind showing you," says the tall, lanky man, lifting his blue,
button-down shirt. "I've shown everyone else."
There, beneath the skin's surface, is the visible outline of the VNS
device.

Seated in an office at his father's Fort Worth business, this
48-year-old father of two recalls in his soft-spoken voice how no
anti-depressant, no therapy ever worked. VNS was a last hope.

"It'll be two years this February," Tucker Davis says. As he tucks his
shirt back in, this well-groomed man describes his lifelong, chaotic
struggle with depression, which landed him in the hospital two times.
Whether his illness was the result of genes or from life, he can't say.
"We'll never be able to peel the onion to know the entire truth," he
says, but offers possible explanations rooted in both.

There's a sister diagnosed with bipolar disorder, a stepfather whom
Davis says was "physically abusive" toward him as a boy, and the family
business that went bust in the late 1980s. (His uncle and one-time
murder suspect Cullen Davis also had a share in it.)

As early as 11, Davis was feeling what would become a constant in his
life: worthlessness. There was the day he decided life wasn't worth
living and, in his bedroom, impulsively threw himself on a pocket knife.
But the tip broke off, and he only succeeded in creating a small wound
below his belly. He never told anyone about it. "When I was depressed, I
didn't see myself as part of the human race," he says.

He married at 24, was a father of two by 30, and was the heir apparent
to his father's hugely profitable mining and truck manufacturing
business, Ken Davis Industries. There was usually some job, some hobby
to help keep his feelings in check. When those inevitable "blue days"
got too much, he'd do karate, skydiving, or deep-sea diving. Jogging,
too. He'd usually feel that "runner's high," the rush of endorphines,
the pain-relieving substance in the brain that can cause a surge in
mood. But the high never lasted for more than a few hours, and
eventually he turned to alcohol. In the early 1980s, life threw its
share of bad breaks at him and his family. The business was in decline,
exacerbated by both the fall in copper prices and the publicity
surrounding Davis' uncle. "That sure didn't help my stress level," he
says. The business held on for a few years with borrowed money, but it
finally went into bankruptcy.

By the mid-1990s, Davis was facing his worst bouts of depression and
suffered two panic attacks so severe that during one of his two hospital
stays, he woke with a memory so impaired that it took about a month to
recover it. The doctors had suggested shock therapy, but the thought of
its most scary side effect, memory loss, kept him away.

For years, those words--darkness, hole, hell--couldn't describe life for
him. Thoughts of death were never far away. "I didn't see it as a
selfish act," he says. "I thought it was no different than dying of a
terminal disease and wanting to be euthanized."

By then, he was talking about suicide almost daily. He assured his wife,
Jilynn, that he wouldn't act on those feelings, but that didn't ease her
fears. Then one night, she saw that he'd written a detailed note on his
computer about his funeral wishes. "When you live with someone suffering
from depression," she says, "it affects every aspect of your life." And
there were many times the two came close to divorcing.

"Living with death daily" is what she calls her years of watching her
husband slip deeper into a depression. She lost a life partner, someone
with whom she could confide in, to share her own worries and fears.

Davis was seeing a psychiatrist in late 1998, when his doctor said that
Rush of UT Southwestern had called, inquiring if he had any patients
who'd run out of chances. "Pure serendipity" is what Davis now calls
that moment.

Davis filled the bill. Soon, he met with Rush and his team. He weighed,
as best he could in his "haze," VNS' side effects, the most serious of
which seemed to be hoarseness of voice, because the device also
stimulates one of the nerves that affects speech.

Several months after the implant, Davis began feeling some slight
changes. The world looked less bleak. The panic attacks stopped. He knew
it wasn't circumstantial; his anti-depressant dosage hadn't been
increased. In fact, it was lower. When a stressful situation would
arise, he no longer felt as if the walls were closing in on him, that he
was about to die.

"I still go through mood changes," he says. "I have my blue days and
good days, but there are a lot more good days now."

His main side effect has been the hoarseness, which comes every five
minutes for a few seconds. At those times, it sounds as if he's being
strangled, but he says that he doesn't feel pain, just slight pressure
on his larynx. If he wants to shut off the device, he can, with the use
of a magnet strapped to his wrist. And though doctors have yet to
attribute use of the device to constipation, Davis says that's also been
a factor.

Whether or not the FDA approves the device, Davis says he's not worried:
"It works for me." Still, he occasionally questions what the long-term
effects of continually stimulating the vagus nerve might be. "I do worry
about that," he says, then quickly adds, "not worry, think about it."

His wife, after all those years of seeing him go from one treatment to
another, was reluctant to believe something was finally triggering
improvement. "When depression becomes a part of your life, it never
leaves," she says. Yes, she sees a change in him, a "return of
confidence," but she still can't conceive of depression ever vanishing
from their lives.

"I have this thing of not looking directly in the eyes," she says,
"because I think people can see inside me, and that makes me ashamed."

Seated near a large window, this woman of 48, who asks that she not be
identified, clutches the sides of her chair. Dressed in a gray, baggy
sweater and full skirt that cover most of her, she all the while averts
the gaze of a stranger.

The shame. Only at the age of 39 in the confines of a therapist's office
was she finally able to speak of her past, of her childhood in the
Midwest, of how she and two other sisters were molested by both her
father and two older brothers. Of the abuse, she says that by "today's
standards," it would be considered rape.
"I'm an incest survivor," she says. "I've been in psychotherapy for 10
years and probably will be the rest of my life." And she's on
medication, which, she says, does little to improve her moods. "After a
length of time, the body becomes immune to it," she says. When not at
work or at home, she's usually in therapy, group and individual.

She finally told her mother about the abuse when she was an adult, and
the answer was swift: "We don't talk about our secrets. Not to
strangers."

Her husband simply told her that the past should remain the past.
They're now divorced.

This woman, who holds a steady, professional job, hides her depression
well. From her clean-cut appearance, her firm handshake, no one at work
would know what she does: that she's tried nearly every anti-depressant
there is, that there's not a day that goes by, not even today, when she
doesn't wish for death, that on weekends, she finds refuge in 18 hours
of sleep at a time. And there was that time, several years ago now, when
she downed a batch of anti-depressants and showed up at her therapist's
office on the verge of an overdose, only to be taken away by ambulance.

Whether her depression is triggered by life events, she can't say. All
she knows is: "After a while, depression becomes its own illness."

"I look at death as peace from torment," she says. But now she knows
that she won't do it, can't, she says, because she doesn't want her
grown children and grandchildren to bear the pain. They're her only
"saving grace."

Almost two years ago now, she turned on the evening news and heard of
the pilot study at UT Southwestern. A participant, a grandmother like
herself, spoke of not finding pleasure in life. "That struck a chord,"
she says. "There are fleeting moments of happiness, but they're always
short-lived.

"When I look at flowers," she says softly, tears just beneath the
surface on this gray, rainy day, "I think, 'How long will they live?'"

The next day, after that show, she called UT Southwestern and soon sent
them her medical records. For nearly a year, she didn't hear back. The
wait, she says, was pure hell. And then, one day, she got the letter.
She was in.

"I look at it as a chance, a piece of hope," she says. She's silent a
moment. "But I do remind myself every day that it may not work."

But what of those childhood memories?

"I don't expect the device to take away the memories," she says
defensively, looking out the window and pointing to a nearby skeleton of
a tree.

"I want to see that tree out there," she says, her eyes narrowing, "and
not see it bare and dead in the wintertime but that in two months it
will have leaves on it.

"I don't have any hopes that it [the device] will make me forget," she
adds. "That's impossible, but it might give me enough of a chemical
boost to give me a different perspective."

Days later, she calls, mentions that her surgery is scheduled for early
March. She sighs. "I'm still trying to hold on for that."














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