Rebooting depression 

Sitting in front of the television a quarter-century ago, “Jay,” a tall, athletic-looking college senior with dark hair, was hit by a bolt of anxiety so powerful that death seemed a mere screen flicker away. His pulse raced. The world went into retreat. “A heart attack,” he told himself. The emergency-room doctor, however, was unimpressed. Jay was too stressed, the doctor said. Other than that, he was “fine.”

Jay returned to his apartment and tried to resume his life despite the unexplained explosions of panic that began to overwhelm him on a regular basis. “I ended up just going through and grinning and bearing it,” he said. Soon he started to find it hard to concentrate. His memory was slipping. He obsessed over his deteriorating condition to the point that the undiagnosed anxiety disorder mutated quickly into deep-seated depression. But unlike many individuals diagnosed with Major Depressive Disorder — about 14.8 million adults in the United States, according to the National Institute of Mental Health — Jay says he never considered suicide. For 25 years he watched the research, trying every new drug he could get hold of, certain that one day someone would create a way out of his torment.

That day arrived on December 16, 2008, when the U.S. Food and Drug Administration cleared, in a less-than-glowing endorsement, a non-chemical, non-surgical depression treatment called Transcranial Magnetic Stimulation. During TMS, bursts of electromagnetic current are directed at an important emotional center of the brain known as the dorsolateral prefrontal cortex. Local researchers believe the creation of a mild electrical current in this area increases blood flow and the uptake of blood sugars. Dr. Fermin Briones, the only doctor in San Antonio currently offering TMS therapy, says the process may also release critical mood regulators like serotonin and dopamine that are typically scarcer in depressed patients. While the FDA, National Institutes of Health, and the American Medical Association have issued statements in support of the technology, there is much scientists still don’t understand about it: What’s the most effective way to deliver TMS? How long do the results last? How does it even work?

Such nagging questions didn’t keep Jay from signing up as quickly as he could. He watched as TMS was approved in Canada several years earlier and even tried to join an ongoing clinical trial at UT Health Science Center at San Antonio, but he couldn’t get off of his psychiatric meds in time. When he hooked up with Dr. Briones’s Institute of Healthy Minds in San Antonio’s medical district in February, he knew as well as he could what he was getting into. The changes began almost immediately. “It was almost like rebooting a computer in my mind,” the middle-aged San Antonio businessman, who asked that his real name not be used, told the Current last week. “The first time I went, I didn’t feel much better. The second day, I got up `and` it was like I felt normal for the first time in 25 years for a brief period of time.”

Magnets have been used as medicine since ancient times in a variety of cultures, including China and Ancient Greece. During the Middle Ages, magnets were prescribed for everything from baldness to arthritis. An explosion of interest followed the discovery of the link between electricity and magnetism more than 100 years ago. While modern science remains skeptical of many of the claims being made in alternative-health circles today, one clinical success appears to be the ability of magnets to help reduce arthritis pain. (Perhaps there was something to that baldness thing, as well?) Magnets were used in the treatment of mental disorders in the West for almost 200 years until the rise of the pharmaceutical industry at the close of World War Two. Magnetism, however, still had contributions to make. It was critical in the development of several medical devices, like Magnetic Resonance Imaging systems, or MRI. But the FDA was forced to think about magnets again — TMS specifically — as not only a diagnostic tool but a therapeutic force because of pioneers like Eric Wassermann at the NIH, Mark George and the Medical University of South Carolina, and Alvaro Pascual-Leone at Harvard Medical School. All three contributed significantly to the body of evidence that eventually got Neuronetics’ NeuroStar device through the FDA approval process. While some federal reviewers were initially skeptical of the therapy’s relatively low level of effectiveness when compared with traditional electroconvulsive therapy (formerly known as electroshock therapy) the reduced risk of damaging side effects played to its favor in the end.

When Dr. Briones — one of the younger-looking psychiatrists I’ve met — has me over to chat, I’m startled by how elegant the TMS chair is. This isn’t one of those steampunk-looking programming devices portrayed in films like A Clockwork Orange or City of Lost Children. It’s not remotely thuggish in a One Flew Over the Cuckoo’s Nest sort of way. It’s as sleek as any high-end dental chair, minus the spit sink, two-tone blue on white. Jay’s head is clamped in place to prevent movement, but his arms and legs are free. “You try to treat at the lowest possible level,” says the young nurse as she programs the device through an attached touchscreen monitor while downing most of a bag of Chewy Skittles. “You’re not trying to zap them. That’s what `electroconvulsive therapy` is for.”

If the sound of the dental chair is the drill’s angry whine, Neuronetic’s recliner is a loud staccato tapping, like a hungry woodpecker attacking a grub-packed gasoline can. “Ah…” Jay says, smiling in earplugs, his neat golf shirt nearly matching the cornflower blue of the device. “There goes the dopamine.” During a typical session, the bursts repeat every 26 seconds for just over half an hour. Once, while the nurse rushes back and forth between Jay, the monitor screen, and her station computer in the front office, the machine beeps, alerting her that the magnetic coil has slipped out of position. As she readjusts, it’s obvious Jay is enjoying the last treatment of a nearly six-week regime. He jokes with the nurse, as she, polishing off her Skittles, teases him back. When I ask how much he has spent on his TMS therapy he responds immediately: “Eight thousand.”

“Wow,” the nurse replies from the other room. “You didn’t have to go for the higher numbers.”

“Six thousand to eight thousand,” he responds, with a whiff of a shrug.

If you were wondering why this miracle cure hadn’t swept the country yet, you just found the first pitfall. Most insurance companies still don’t cover the procedure. But Jay says he plans on fighting for reimbursement anyway. And in the very near future, TMS is expected to become a regular addition to the psychiatrist’s tool belt. Research around the country is probing TMS’s ability to treat a variety of maladies beyond depression. TMS has shown positive preliminary results in the treatment of auditory hallucinations, epilepsy, obsessive-compulsive disorder, migraines and chronic pain, Parkinson’s, and phantom limb disorder. It has definitely captured the imagination of researchers at the University of Texas Health Science Center at San Antonio, who are working to increase the effectiveness of TMS for depression by refining the way it is delivered with their own patented system.

In the basement of the McDermott Clinical Science Building, a research subject in white T-shirt and Frankie Valli hair is lying on his back bouncing electrode-tipped fingers in rapid succession on a tabletop. He introduces himself as David. Taped to a screen above him is an outline of his left hand. Each finger is numbered. His wired fingertips click out a memorized pattern, their rhythm like primary-school tap students. One and two-and-three-four. Two and two-and-three-four. “Of course, I’m very experienced. You can tell that,” he laughs.

After completing several four-minute tapping exercises, a research assistant in a white lab coat binds David’s head against a rigid two-by-four with a nylon strap. She then attaches a double coil of conducting wire that resembles a capital letter B to a robotic arm, combs the pen-shaped tip of a mechanical digitizer through his pompadour, feeding coordinates to the computer, and guides the arm into place above and to the right of the his forehead. Soon the room is filled with the sound of mechanical taps; the woodpecker is on the loose. The magnetic pulses fire with a metronome’s regularity into David’s brain. But in this exercise they aren’t trying to stir the seat of emotional well-being. Instead, researchers here are targeting the motor cortex, the part of the brain associated with voluntary physical movement. David wears earplugs to dampen the noise. But apart from the risk of headache and a remote chance of seizure, there are no other side effects reported in the scientific literature on TMS.

David is one of four people receiving magnetic stimulation to the portion of his brain’s motor cortex associated with hand movement. Another four participants, the “control” group, go through all the same motions, hear the sets of clicking, but don’t receive the bursts of electromagnetic energy.

Dr. Shalini Narayana, head of the electrophysiology division of UTHSCSA’s Research Imaging Institute, expects the stimulation of the brain’s motor cortex will improve the performance of manual tasks, in this case a choreographed finger dance. If the motor-skills trial is successful, Narayana says she hopes they’ll next target sufferers of Parkinson’s Disease. Other possible applications include better diagnosis for the many returning soldiers with symptoms of post-traumatic stress disorder and traumatic brain injury.

Dr. Narayana is also working with Dr. Peter Fox, the director of the Research Imaging Institute, and Dr. Pedro Delgado, the head of the psychiatry department, with a small group of volunteers suffering from depression. Though FDA-approved for two years for sufferers of Major Depressive Disorder, TMS still only offers respite for about 40 percent of patients, Narayana says. Part of the reason those numbers remain under 50 percent could be the imprecise way TMS is delivered. The dorsolateral prefrontal cortex, an important center of emotional activity often found to be lethargic among depressives, is a tough spot to eyeball. By contrast, the motor cortex is a fairly obvious group of neural fibers that cross from the top of the brain behind the ears, and to the back of the neck. For that reason, clinicians preparing to give TMS therapy are instructed to first find the motor cortex by eliciting finger movement with a magnetic burst and then move the coil five centimeters forward.

“It’s a very crude way of targeting,” Dr. Narayana said. “What we’re saying is, yes, we know TMS works, but if you target it better, if you apply it better and more accurately and more consistently, we are saying you will have a better outcome.” With use of a robotic arm to guide delivery, she thinks positive results can be boosted above 50 percent.

Dr. Pedro Delgado, chair of the school’s department of psychiatry, is more guarded.

“TMS is safe. It’s easy to use. And it provides a very different mechanism of action than other treatments,” he said. “That combination makes it of interest because it opens the possibility that some subset of people that wouldn’t ordinarily respond to a medication … could benefit from this.”

That’s the good news. Younger people, who can experience suicidal thoughts as a side effect of some anti-depressants, should be offered TMS before chemical therapy, Delgado said. Pregnant women, who shouldn’t be on any such drugs, are also good candidates for TMS.

“I think the biggest problem with TMS is … there’s daily or every-other-day trips to the doctor to get it, and that’s over several weeks,” he added. The high cost is partly driven by the device’s only existing manufacturer, which charges $100, half of the typical cost for the service, for a non-reusable pad intended to keep the muscle on the side of head from contracting. “At this point, even if you had the device for free, you’d still be stuck paying the stupid $100 for Neuronetics,” Delgado said.

And yet, for some patients, dollar-to-dollar comparisons may favor the TMS chair over pharmaceuticals. When Jay walked out of Dr. Briones office last week, it was unclear when — or if — he’ll need to return for follow-up treatments. “Exactly how long people will continue doing well, or whether there’s a subset that actually stay better longer with this is unclear,” Delgado said. “So far, the data have actually been better than expected.”

With enthusiasm returning to his life, Jay has a hard time putting away his animosity for the lost years. The psychiatrists were ever eager to offer him new pills (he estimates he’s tried about 15 over the years) and hope for that “Hail Mary” pass, but no one had a solution for him. “Even in the age of Prozac and all the new drugs that are supposedly revolutionary that came out, none of ’em ever really worked,” he said. “They actually made me feel much worse.”

For years, he followed closely the developments he saw happening at the Medical University of South Carolina and waited. “What I was looking for was exactly what TMS was. It was kind of looking for a key to get out of hell free. Well, not free, but basically get that key that gets you better to a point where you feel much better about your place in life.” As more research papers are published about the possible applications of TMS, Jay wonders why nobody tapped into it sooner. “It’s such an easy treatment that I cannot believe that somebody never thought about this or pushed this or commercialized it. It was like a miracle. It’s a cure.” •

A conversation with Dr. Narayana at UTHSCSA.



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