A Jolt to the System
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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