Medical Magnetism

The Baltimore Sun

Sixteen years ago, Steve Zatuchni was a computer sales manager, making a six-figure income. Then all hell broke loose in his brain.

He became severely depressed, to the point that he could no longer work. He slept up to 18 hours a day, and when he was awake, felt so miserable he wished he were asleep. He tried dozens of medicines, in myriad combinations. Nothing worked. Distraught, he tried to kill himself several times.

Then, in 2004, he enrolled in a study of an experimental therapy called transcranial magnetic stimulation, or TMS -- a noninvasive treatment that sends magnetic pulses into the brain.

It worked. "Within a week, the depression was lifting," he says. "Within two months, it was gone. TMS saved my life." Zatuchni, 59, who lives in the Philadelphia area, no longer takes any medicine.

Stories like Zatuchni's are no surprise to a growing group of researchers, therapists and entrepreneurs. Proponents -- including scientists at Harvard, Yale and UCLA -- say TMS could transform treatment for depression as well as a range of other ailments, including schizophrenia, migraines, insomnia, epilepsy, chronic pain and Parkinson's.

"It's extremely promising," says Dr. Abraham Zangen, a TMS expert who does research at the Weizmann Institute in Tel Aviv, Israel. "TMS could revolutionize psychiatry. It's a completely new approach."

Meanwhile, over the past two decades, hundreds of small studies have found TMS both safe and effective. Among them:

Yale researchers reported that TMS can eliminate auditory hallucinations suffered by many schizophrenia patients.

Harvard scientists have shown that the treatment can reduce what was thought to be intractable chronic pain.

A team at Columbia University used TMS to improve memory in people suffering from sleep deprivation.

Although TMS is already used in several countries, including Germany and Canada, it is not yet approved in the United States. But that could change later this year if the Food and Drug Administration decides to allow it as a treatment for migraines.

Early last year, in response to an application from a TMS device maker, an FDA panel decided the treatment was safe, but didn't work better than a placebo. The company, Neuronetics Inc. of Malvern, Pa., plans to reapply later this year.

Maryland inventor Robert Fischell has put his efforts into a hand-held TMS unit (most are currently the size of a desktop computer). The device is undergoing a clinical trial for migraine treatment.

"With a little luck, it'll be on the market by the end of the year," says Fischell, who also started a company, called Neuralieve, to produce it.

Fischell, a former Johns Hopkins physics professor who lives in Howard County, has invented dozens of medical devices over the past 40 years -- including the rechargeable pacemaker, implantable insulin pump and a variety of stents to help unclog coronary arteries.

He says that in most cases his new invention can relieve a migraine with just two magnetic pulses delivered over a few seconds. "It says, 'Neurons, whatever you're doing, stop it,'" Fischell says.

In November, a nationwide trial sponsored by Neuronetics found that TMS improved depression in a significant number of subjects. (Zatuchni was part of this research.)

In the study, chronically depressed subjects received TMS for 35 minutes a day, five days a week, for four to six weeks. Depression improved significantly in a quarter of the volunteers -- double the rate of a control group that had a sham TMS treatment (subjects were hooked up to the TMS device but didn't receive magnetic waves).

Dr. John O'Reardon, an associate professor of psychiatry at the University of Pennsylvania and lead researcher in the study, says the 1-in-4 success rate is actually quite good, given that the subjects suffered from "treatment-resistant depression," i.e. they had tried many medicines and therapies without success.

"These are the toughest patients to treat," he said. "This was a significant improvement." He notes that once the control group was also given TMS, the success rate shot up to almost half of all subjects.

TMS was developed in the mid-1980s as a research tool to help scientists understand how the brain works. It uses magnets to generate a powerful field, creating an electric current that alters brain waves. Scientists soon realized that many patients in TMS studies seemed to improve, and increasingly researchers have focused on its therapeutic potential.

It is not entirely clear how TMS works, in depression or any other ailment. Researchers know the treatment can change electrical activity in targeted brain regions; low-frequency magnetic waves decrease neuronal firing, while high-frequency waves increase it.

In depression, researchers have focused on the left prefrontal cortex, a part of the brain that plays a large role in regulating emotion and memory. Treatment involves sending high-frequency waves into this area, on the upper left forehead.

In the migraine study, subjects place the 3-pound device at the back of the head when they feel a headache beginning. The press of a button sends two high-frequency waves into the brain. The lead investigator in the trial, Richard Lipton, a neurologist at Albert Einstein College of Medicine in the Bronx, says the pulses act as a kind of "reset" switch that stops the electrical storm causing the migraine.

If the FDA does give approval, TMS could change the treatment landscape. Lipton estimates that "millions" of migraine sufferers -- there are 35 million in the U.S. -- could eventually use the Neuralieve device.

Psychiatrist Scott Aaronson, director of research at the Sheppard and Enoch Pratt Hospital, estimates that a third of depression patients don't improve with current therapies -- and may be helped by TMS.

"We're likely to be able to treat people we haven't been able to help before," says Aaronson, who was one of the investigators in the Neuronetics trial.

Most depression patients are treated with drugs such as Prozac or Effexor; these medicines often don't work, and more than half of patients taking them suffer serious side effects, including drowsiness, weight gain and loss of libido.

For those who don't improve or can't tolerate the drugs, there are a variety of treatments that directly target the brain. The most effective is electroconvulsive therapy, or ECT, which works about two-thirds of the time. Although ECT is much safer than it was in its heyday 60 years ago, it still poses real risks -- particularly short-term memory loss.

Two other electrical therapies are sometimes used: DBS (for deep brain stimulation) and VNS (for vagus nerve stimulation). Both require surgery for permanent implantation of electrodes.

TMS, by contrast, is noninvasive and has almost no side effects. Some patients feel an uncomfortable tingling in their scalp during the first few sessions, O'Reardon says. But because it stimulates a specific brain area rather than the whole body, as drugs do, or the whole brain, as ECT does, TMS has far fewer unintended consequences.

TMS does have disadvantages. It is expensive: A round of treatment typically runs between $5,000 and $7,000. Even if the FDA approves it, insurance companies may be reluctant to cover the cost. And it can take time: an hour a day for several weeks for treatment of depression. Some worry that the improvements produced by TMS may not last more than a few days or weeks.

But many researchers -- and patients like Zatuchni -- say TMS patients may need repeated treatment to keep brain circuits working properly.

Zatuchni goes for such sessions every two weeks, which, he says, keep him stable and happy. Since his TMS treatment began, he has begun work on two novels; he's almost finished one and has hooked up with an agent.

"I just wish I had gotten it 15 years ago."

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