By Jared Chausow
By Katie Toth
By Elizabeth Flock
By Albert Samaha
By Anna Merlan
By Jon Campbell
By Jon Campbell
By Albert Samaha
The things that have been done to Colleen Kelley's brain sound like scenes out of a retro psych ward where ice-pick lobotomies are still the norm and Nurse Ratched doles out electroshock. Her brain has been scanned, doused in experimental drugs, magnetized, and electrified. She has been cut open, prodded, and implanted with foreign objects. Her memory has been erased.
But Kelley isn't a "psychiatric survivor" fighting to ban electroshock, or a memoirist detailing her horror stories of a time long ago. She is an educated woman, never hospitalized or locked in a mental ward, who has spent the last decade volunteering for treatments that her doctor calls the "experimental edge of psychiatry." Kelley has submitted willingly and continues to offer her brain up for experimentation. "I want my brain drained," she wrote to the Voice during a series of e-mail and phone interviews detailing her years as a guinea pig for psychiatric experiments in Maryland and New York. She suffers from a severe, stubborn depression that doesn't respond to medication. Her doctor of 15 years describes her as chronically suicidal, and Kelley talks about offing herself as easily as others might speak about trouble with their in-laws.
She has a loving partner, a comfortable house half a block from the Anacostia River in Cottage City, Maryland, and, until her depression became debilitating, a satisfying career in graphic arts and desktop publishing. She insistsand her doctors agreethat her depression is biological, rooted in a dysfunctional brain. Her brain has turned against itself, eating itself from the inside out with thoughts of death. Kelley likens the suicidal urge to "a finger constantly wiggling at the back of your throat. You know you wouldthat you willfeel better if you only puke."
In addition to dozens of antidepressants, antipsychotics, and all manner of off-label and experimental drugs, she's also tried yoga, acupuncture, dietary changes, supplements, Lyme-disease treatment, mercury-amalgam removal, and flower essences. "The ignorant hope that there is something I can do to alleviate this misery keeps me going," she says.
To treat medication-resistant patients like Kelleythere are an estimated four to eight million of them in the U.S.neurologists and psychiatrists are increasingly turning to the one tool they know directly changes brain function: electricity. The most infamous form of this is shock treatmentnow called electroconvulsive therapy, or ECTbut new modes of electromagnetic-based treatments, broadly called brain stimulation, are being tested on willing patients at New York State Psychiatric Institute and Columbia University Medical Center.
Dr. Sarah Lisanby, who runs the brain-stimulation lab at the medical center, admits that the stigma from the old days of ECT still lingers, despite significant improvements in the procedure. "If you only see portrayals like [One Flew Over the] Cuckoo's Nest, naturally people would be afraid," she says. But ECT, as demonized as it is, has inspired strange and promising new treatments, such as surgery to implant electrodes in the brain or neck. In one configuration, wires under the skin connect electrodes to a pacemaker-like device implanted in the chest that administers regular pulses of electricity to the brain. Other, nonsurgical forms of experimental brain stimulation are less invasive, but no less fascinating: One treatment uses magnetic fields to cause a seizure similar to ECT, while another directs very-low-voltage currents to the brain while the patient is awake. In all of these treatments, the idea is essentially the same: to reboot the brain, changing the way it actually functions.
For some, the experimental therapies have had astonishing results: Patients with Tourette syndrome abruptly stop having tics, and depressed people snap back to life. Despite these promising results, doctors admit that much of what worksand what doesn't, and whyis still a mystery. They warn that these treatments are not cures, that they are very experimental, and that the long-term side effects are still unknown. But the patients who end up at the brain-stimulation lab are often willing guinea pigs, impelled there by the mystery of their illnessthe causes of most psychiatric disorders are still poorly understoodand the desperate desire to fix their malfunctioning brains.
"It is a win-win situation," said Kelley. "You either die a hero during the procedure, thus donating your body to science while still alive, or you survive the surgery with an iota of a chance that the wacky theory and device just might work."
Kelley's journey into the labyrinth of experimental treatments began 15 years ago, when she was officially diagnosed with major depressive disorder at age 29. She had known for years that something was wrong: In college, where she graduated magna cum laude with degrees in English literature and fine arts, she consumed espresso by the pot, alcohol by the liter, and clove cigarettes by the carton, self-medicating the unnameable thing that kept her awake all night and numb all day. After accepting that it wasn't simply the blues, or hormones, or a dozen other ailments she was tested for, Kelley started on a pharmaceutical merry-go-round, trying out scores of antidepressants and other meds, none of which helped very much. Previously the chatty, likable life of the party, Kelley was transformed into an erratic and hostile mess. Deb, her partner of 23 years, remembers coming home to find Kelley slashing a stuffed animal with a razor blade or silently sitting in the closet.
Throughout those early years of her depression, Kelley was able to hold down a job in downtown DC working as the publications director for a trade association. But when that became unmanageable, she began working from home as an independent contractor, where her insomnia and bizarre sleeping habits would go unnoticed by clients. After several years, the depression obliterated her ability to concentrate and Kelley quit working altogether. She went on Social Security disability in 1998.
Deb, an elementary-school teacher, got into the habit of calling home four times daily just to make sure Kelley was still there, still alive. She would arrive home each evening with her heart in her throat, afraid of what she would find on the other side of the door.
After exhausting a long list of antidepressant medications, Kelley began "volunteer work" as a pharmaceutical lab rat, hoping that some experimental drug might ease her depression. She started off close to home, at a drug trial at the National Institute of Mental Health (part of the National Institutes of Health) in Bethesda, Maryland. After a doctor there refused to let her go home one day, afraid that Kelley would harm herself, she was referred to an experimental treatment that was supposed to be a kinder, gentler form of electroconvulsive therapy.
While ECT runs electricity broadly across the brain and induces a seizure, this newer treatment, called transcranial magnetic stimulation (or TMS), uses magnetic fields that induce much weaker, more focused electric currents directly to the area of the brain responsible for mood regulation (called the left prefrontal cortex). It's much more focused than ECT, doesn't cause seizures, and doesn't require anesthesia, so the process is considerably less intimidating.
Before receiving TMS, Kelley underwent a series of brain-imaging scans that were used to pinpoint the specific area to be targeted. She was injected with radioactive fluid to "light up" her brain and directed to lay down on a table, where researchers placed a polymer mask on her face to keep her from moving during the scan. The mask, still warm and malleable ("like a sci-fi facial," she says), hardened as it cooled. After reviewing the scans, researchers held a magnetic coil shaped like a figure eight over Kelley's scalp. When turned on, the stimulator emits a clicking sound over the noise of a vacuum cleaner. As it pulses on and off, it delivers little rubber-band snaps of electricity to the scalp for 30 minutes to an hour. These treatments are normally done multiple times over a period of weeks. Various recent studies have shown TMS to benefit about 30 percent of depressed patients, according to Lisanby.
At the time that Kelley was receiving TMS treatments in Bethesda, the brain-stimulation lab in New York began testing the procedure as well. Today, the lab is a leading center for TMS studies. In addition to being tested to treat depression, the brain-stimulation lab has studied its memory-enhancing effects on sleep-deprived soldiers and Alzheimer patients. The lab has also been a major player in the quest to get the FDA to approve the treatment.
Neuronetics, the Pennsylvania-based firm that manufactured the TMS device, presented the results of a study conducted in part at the brain-stimulation lab to an FDA advisory panel in January. Dr. Lisanby told regulators that she believed in the device: "As a psychiatrist that specializes in treating patients with medication-resistant depression who are frequently hopeless, I know that the only thing worse than no hope at all is false hope, and it's my personal evaluation of the data that TMS is not false hope."
Twenty years of Colleen Kelley's memory was erased by electroconvulsive therapy, but she is still trying new forms of electro-magnetic treatment to ease her severe depression.
"After being hospitalized, trying more than 30 different kinds of antidepressants that caused me to suffer major side effects, experimenting with other kinds of medications, attending about two years of psychotherapy and definitely not even considering ECT for the bad reputation associated with it," Frankel said, she decided to participate in a TMS trial led by Lisanby. "At first, TMS was painful," Frankel reported. "It felt like an intense snapping of a rubber band on my head. However, in a short time I became accustomed to the sensationit was quite relaxing and usually put me to sleep." After a series of sessions, Frankel felt the depression lifting, and she urged the FDA to approve the device so others could be similarly helped.
Another patient, who said he'd lost more than 17 jobs because of debilitating depression, told the panel: "When TMS showed up on my horizon, I decided I would try that and then ECT, and if neither worked, I would strongly consider suicide." TMS chased the suicidal thoughts out, he said.
Despite these glowing testimonies, the hearing didn't go well for Neuronetics. The FDA advisers recommended against approval, citing worries that the device hadn't been proven significantly effective and wanting to see further study. So, for now, TMS remains an experimental treatment that can only be administered to patients in clinical trials. In the past year, the brain-stimulation lab has used TMS to treat about 30 people and continues to test it on patients with depression, depersonalization disorder, obsessive-compulsive disorder, and schizophrenia, and hopes to tweak it to be more effective for treating a whole range of psychiatric disorders. In the meantime, psychiatrists continue to send thousands of their clients for the more invasive but available treatment: ECT.
And that's what happened with Kelley after TMS eventually proved ineffective for her. At that point, "she had tried pretty much everything I or others could think of," said Dr. Suzanne Griffin, Kelley's psychopharmacologist of 15 years. From the start, Kelley was horrified at the thought of ECT. "She went into it kicking and screaming," recalled Deb.
No wonder, considering ECT's contro-versial history. It has been used to "treat" homosexuality, was given to punish uncooperative psychiatric patients, and was sometimes performed without anesthesia. But in 1999, the year that it was recommended for Kelley, ECT was in the middle of a comeback. The U.S. surgeon general had just released a controversial report promoting it as a highly effective treatment for the most severely depressed patients, and psychiatrists were touting the many improvements they had made to a once-barbaric treatment. ECT is now administered with anesthesia, oxygenation, respiratory support, and muscle relaxation. It uses lower currents, and scientists have tweaked the placement of the electrodes to minimize side effects. It has recently gained the vocal support of Kitty Dukakis, who co-authored a 2006 book detailing how ECT changed her life. Even as the shock treatment gained new followersan estimated 100,000 Americans now receive ECT annuallymany critics still call for it to be banned outright because of its devastating side effect: memory loss.
Kelley began getting three treatments a week. Her suicidal depression was replaced by a mindless stupor. After the first treatment, a nurse wheeled Kelley out looking disheveled and disoriented. She was sent to the cafeteria, where she sat "drooling milk out the sides of her mouth," Deb said. At home, Kelley couldn't empty the dishwasher because she couldn't remember where the dishes went. The only thing she was able to do was veg out on the couch watching football.
After 33 sessions, Kelley pulled the plug on the treatment when it was apparent that the side effects were lasting. She had lost 20 years of memory. Everything she knows about her life from the years 1979 to 1999 comes from photographs, medical records, and overheard conversations. After her mother died last year, friends and family tried to console her by saying that she would always have her memories, but she wasn't able to admit to them that she actually couldn't remember much about her mother. "I have a photograph of the two of us, but I can't emotionally connect," Kelley says. "I don't recognize my mother, and I don't recognize myself."
Nevertheless, she was alive and no longer suicidal. "When you get knocked senseless by a two-by-four, you're not thinking about how depressed you are," Kelley wrote. "At this level of depression, most doctors are elated that you are still alive after they treat you. They congratulate themselves on saving another [void-of-quality of] life" (her aside).
Kelley stopped the ECT in April 1999. By November of the same year, she was already searching for something else. What she found was even more shocking.
A sculpture made by Peter Bulow, a researcher at the Columbia brain-stimulation lab, with a device attachedcalled the transcranial direct current stimulator.
Kelley applied for the brain-stimulation lab's VNS study in November 1999. Researchers called her on Christmas Eve and told her to be ready for surgery on January 10 at New YorkPresbyterian Hospital. The news came at a crucial time: Her doctor described her as "chronically suicidal [and] severely despondent" when she entered the study. As before, she wasn't eating, sleeping, or bathing. The energy she did have was devoted to medical appointments.
Deb remembers thinking that "[Kelley] agreed to do it because her hope was that someone would mess up during the operation and she would die and then it wouldn't be suicide; it would be donating her body to science. I, on the other hand, was hoping beyond hope that it would work."
During the course of the study, Kelley stayed with relatives in New Jersey and commuted to the Washington Heights hospital. Although one of the eligibility requirements was that patients live in the vicinity, she was surprised to learn that several other participants were also temporarily living with nearby relatives or traveling long distances. Among them was Michele Merdinger, a Philadelphia resident with bipolar disorder. Like Kelley, she had tried dozens of medications and ECT, all to no avail. Her life had been ravaged by the illness: She lost numerous jobs, was hospitalized more times than she cares to remember, and could barely maintain friendships.
For both women, the surgery was uneventful. The procedure, usually about $15,000, was free to them as subjects of a clinical trial. The $12,000 battery-operated stimulator, donated by Cyberonics, the manufacturer, was inserted into the chest just below the skin. Electrical leads were connected to the left vagus nerve. The surgery took less than an hour and barely left a scar.
During the hours the two women spent together on weekly follow-up visits to the lab, Merdinger and Kelley compared notes on how the VNS was working. It was unclear at first if the device was doing anything but making them uncomfortable. Every time the stimulator fired, a 30-second pulse of electricity was sent up the wire and to the electrode on the vagus nerve, giving them a jolt that they could feel.
"I would get excruciating pain through my jaw and through my teeth," Kelley said, although that was fixed by a minor adjustment to the device. "I would make these weird moo-like sounds in my sleep because I had it turned up so high. It was rattling my vocal cords."
After about nine months, Kelley was the first of the two to feel her depression begin to lift. Unlike some medications, which painted over the depression with a chemically induced detachment or energy, the VNS actually seemed to sweep the depression away. "It was a complete remission," she said. Meanwhile, Merdinger was improving at a much slower pace. "It almost crept up on me," she said. "There was never one day where I could pinpointI just remember being able to look back and say, 'I feel a hell of a lot better today than I did a couple months ago.'"
Both women were among the 29 percent in the study who felt their depressions melt away within a year after surgery. In 2002, Lisanby and her colleagues published those findings in the journal Biological Psychiatry, describing the results as slow-acting compared to ECT, which can have an antidepressant effect almost immediately, or medication, which usually takes a couple of weeks to kick in. Despite the snail's pace, both researchers and their successful subjects were excited that the radical new treatment was effective on people who'd never responded to anything else. Re-energized and feeling alive again, Kelley testified at a 2004 FDA hearing for the device.
"I am not going to idealize nor sentimentalize the device," she told the panel. "I know I am one of the third who have responded to it. I know there are others who continue to suffer the burden of treatment-resistant depression. I see it in their faces as I sit in the lobby and wait my turn at my site. I know that pain I suffered it prior to the VNS. Still, I have windows of it now and again." But the option to receive this potentially life-saving surgery, she added, should be made available to others.
The FDA approved VNS as a treatment for depression in November 2005, and the brain-stimulation unit ( in collaboration with New YorkPresbyterian Hospital ) became the first place in the metro area to provide it. Soon after the FDA approval, both Merdinger and Kelley had replacement generators implanted, which were donated once again by Cyberonics. The new devices provided a much longer battery life.
Unfortunately, Kelley's FDA speech turned out to be prescient of what was to come. Soon after, those windows of depression that she'd hinted at became more frequent. "I'd have three good weeks and then three bad weeks. We'd adjust the parameters, and then I'd have three good months and then three bad. More adjustments." After she'd maxed out the settingsthey were so high that she had to endure air obstruction, jaw pain, hoarseness, and muscle spasmsshe went back on medication. Lisanby has a few theories about why the device stopped helping Kelley, but ultimately, she said, "it's a mysterywe simply don't know."
Steve Blackman receives treatment for Tourette syndrome.
Kelley turned the device off last year as a prerequisite to enter another drug trialwhich also failed to help herand hasn't turned it back on since. Now, two years after VNS was approved for depressionand seven years after Kelley and Merdinger were implanted a new controversy is brewing over the device. In February, the Centers for Medicaid and Medicare joined Blue Cross/Blue Shield in its decision not to cover VNS to treat depressed people. (Many health-insurance carriers don't have clinical guidelines for VNS coverage, and patients have reported that they were only able to get coverage after a lengthy appeals process.) The insurers weren't sold on the effectiveness of the device, and the FDA had concerns that subjects in some VNS trials were reported to have attempted or committed suicide. (Lisanby said that she knew of one suicide by a patient at the brain-stimulation lab, but declined to comment further for fear of giving any identifying characteristics. It's unclear if that patient was in a VNS study or had undergone a different treatment.) Even the U.S. Senate got involved in the debate, with Republican Senator Charles Grassley of Iowa ordering an investigation into the initial VNS review process.
At a panel hearing to review the device after FDA approval, representatives of Public Citizen's Health Research Group and the National Research Center for Women and Families spoke out against the VNS approval, concerned that the device hadn't been proven effective for a significant portion of depressed patients. "When treatments don't work and the person being treated is depressed, that can contribute to the depression, because it contributes to that sense of hopelessness and failure," warned Diana Zuckerman, president of the National Research Center for Women and Families. "If [VNS] fails, that could actually contribute to the depression, make them feel more hopeless, and even potentially contribute to suicide down the road."
Despite having given up on VNS herself, Kelley remains adamant that it should be made available to others. "I don't care if only 20 percent of the people respondI could be one of those 20, and you can't take options away from people who are this sick." She is clearly still suffering from her own illness and looking for other options, especially since her depression returned with a vengeance this spring. She would go days without showering or dressing; eating seemed like a pointless chore. She spent her time isolated on the porch, not doing or saying anything. When she did talk, it was often about her plan to drive her car off a bridge.
"Years ago, I tried to argue with it and fight with it," Deb said, but she has learned that arguing doesn't work. Now, she just listens, sheds tears along with Kelley, and does what she can to comfort her.
At one point a few months ago, Kelley began taking her medication more frequently than directed, perhaps in an attempt to overdose, when Deb confronted her about it: "It wound up being my pure, blunt emotion of just crying and saying, 'Please don't do this!'and she stopped." For the next two weeks, Deb stayed home from work, scared to leave Kelley alone.
"I don't know how she hasn't offed herself," Deb admitted quietly. "It got to the point where I said to her, 'If that's what needs to be done, if you can't stand it anymore, I will support you.' It's so frustrating and hard to watch someone suffer like that."
Merdinger feels the frustration as well. "One thing about depression is, once you leave it, it's difficult to remember how bad it was. . . . Sometimes, when I look at her, I almost want to say: 'Snap out of it!' But I know that never worked for me. . . . We sat there side by side, and I almost expect her to be a success too, because we went through this together. It's hard to watch somebody you care about, to almost leave them behind as you go forward. I feel guilty."
Despite the frustration of so many failed treatments, both Deb and Merdinger have urged Kelley to keep looking for a new experiment. "I want her to keep going, to keep trying," says Merdingerand there is one thing left that she has yet to try
Psychiatric brain surgery has come a long way since the lobotomy. If Kelley were a clinically depressed patient in the 1940s, that early form of psychosurgery may have been attempted, and most likely would have left her brain-damaged. Back then, psychiatrists just destroyed the general area of the brain they found problematic. Today, they can pinpoint the specific area associated with the neurological or psychiatric disorders and carefully alter it. That's the idea behind deep-brain stimulation, a surgical procedure that places electrodes in the brain.
In deep-brain stimulation, or DBS, a pacemaker-like device in the chest provides a steady flow of electrical pulses to two electrodes implanted deep within the brain. The placement of the electrodes depends on the ailment they are meant to treat: For years, patients with Parkinson's disease have undergone FDA-approved DBS surgery, and researchers have recently begun using experimental DBS to treat other neurological and psychiatric disorders.
A polymer mask used during brain-imaging scans
In addition to depression, DBS has also produced successful results for Tourette patients. Probably the example closest to home of a post-DBS patient that Kelley can look to is Steve Blackman, a Monticello, New York, resident who underwent the surgery at Yale to control a severe case of Tourette syndrome in 2004. He was the second person in the world to get DBS for Tourette. His case provides a fascinating link between the world of movement disorders and psychiatric disorders, since Tourette can arguably be categorized as both.
Blackman was diagnosed with Tourette at age three. He used to have vocal tics that were sometimes nonstop. "I was screaming, I was yelling, I was just totally out of control," he recalled. Now the vocal tics have disappeared; what persistsalthough at a much-reduced rateare the physical tics. At irregular intervals, Blackman's head snaps forward forcefully and then back, as if he's in an invisible car crash over and over again. He has chronic whiplash and permanent spinal damage from the tics. He uses a leg brace and cane to get around, and has had several surgeries to relieve the neck and back pain caused by the tics. Before the DBS treatment, he had up to 2,000 of these neck-jarring tics each day; now he usually has fewer than 100. "It's saved my life," Blackman said.
Since childhood, he has experienced only a brief period when he was completely tic-freejust after the DBS surgery in 2004. For a few weeks immediately after the device was implanted, but before it was actually turned on, Blackman's tics completely disappeared. His doctors were stunned, since he wasn't receiving any electrical stimulation yet. "It is still not understood exactly how DBS works," said Dr. Alain C.J. de Lotbiniere, Blackman's neurologist.
On a sunny August afternoon, when Blackman came to see de Lotbiniere in his White Plains office, it was apparent that much of DBS is still in the trial-and-error stage. As in most of the brain-stimulation studies, the device's manufacturer works closely with researchers to develop and test the stimulators. Blackman's brain stimulator was made by Medtronic, and a representative of the company attended the doctor's appointment to help de Lotbiniere figure out why, over the last month, Blackman's tics had gotten worse. Despite the combined total of eight fancy acronyms after their names and decades of experience, both admitted that they still don't know exactly how DBS works, or why, in this instance, it was faltering. After they ruled out a flagging battery in the stimulator, the tweaking began.
Blackman sat in the middle of the office, with de Lotbiniere and the Medtronic rep standing over him. The duo conferred over a "physician programmer," a touch-screen remote control for the deep-brain stimulator that looks like an oversize Palm Pilot. Rather than controlling a calendar, however, this programmer controls the electricity going into Blackman's brain. Press a button and the voltage goes up; touch another and the pulse width goes down. The Medtronic rep directed the doctor through multiple choices on the tiny screen. They tweaked and debated, then announced that they had turned up the voltage.
"Is anything happening?" de Lotbiniere asked.
"I can't open my right eye," Blackman said. "Is my eye open?" He grimaced as his neck and head snapped forward uncontrollably.
The settings were adjusted again.
"Whoa! I don't know what you're doing, but I feel somethingI don't feel good . . . I'm having a lot of problems moving my eyes. My actual eyeball is hard to move," Blackman told them.
A final tweak, and de Lotbiniere and the Medtronic rep declared the adjustment complete. They had changed the width and frequency of the electrical pulses and amped up the voltage. Meanwhile, Blackman had regained most of his eye movement (apparently, his electrodes are implanted near an area of the brain that controls this). If the adjustment doesn't minimize his tics, he may have another round of surgery to get an additional two electrodes implanted in a different part of the brain.
"It's hard to accept that this is the best we can do," said Dr. James Leckman, another of Blackman's doctors and a Tourette specialist at Yale who has collaborated with the New York brain-stimulation lab. "He's a good example of how ignorant we still are."
Researchers at the lab will look into prior research on Blackman and the Toronto patients to replicate and improve DBS for depressed patients. Kelley has been anxiously awaiting her chance to enroll in that study.
When DBS was explained to her, Deb said, she "was scared to death with the thought of somebody cutting open [Kelley's] head and sticking rods in it and playing with her brain," adding: "It's not only experimental, it's dangerous experimental. But when you are that sick and nothing else works, you'll do whatever. If someone said to her, 'You have to cut off your right arm and left leg to be well,' she would probably do it."
Suicidal thoughts, Kelley said, are still a "constant companion." She feels as if it's the one true way to end her depression, the only one that won't disappoint her. "I just need reliefI'm so tired of treading water," she said. "If the DBS study falls through, I am going to have to re-evaluate my reasons for living." Kelley has already made arrangements for her death: In a fit of morbid activity last year, she did all the paperwork necessary to donate her brain to Harvard for postmortem research into depression.
Lisanby said she doesn't know when enrollment for her DBS study will begin, but she has urged Kelley to hold out. "Despite going through all those disappointing treatments, she keeps trying. The field is right there with her, trying to find solutions. She shows that one can bear it and maintain hope," Lisanby said. "There is a reason for that hope."