When patients with severe depression don't respond to medication, they are often prescribed electroconvulsive therapy, or ECT, in which an electric shock is used to simulate activity in the prefrontal cortex -- frequently easing their symptoms.
It's effective, but it has significant side effects. The reason is that there is no way to confine the current to the prefrontal cortex. The electricity, delivered to the skin, floods the entire brain, stimulating areas that trigger seizures and memory loss. And ECT has a long, dark history, from an era when voltages were much higher than now used, which still makes it intolerably scary for many patients.
It's also expensive, in part because it requires a physician's supervision. Psychiatrists have long sought something better.
Many now believe they have found it. The treatment is repetitive Transcranial Magnetic Stimulation, or rTMS, in which the prefrontal cortex is stimulated with a magnetic field -- rather than an electrical shock. The shape of the field can be controlled so it's confined to where it's needed, eliminating the side effects of ECT.
rTMS is also much less expensive than ECT. But is it cheap and effective enough to justify its use as routine treatment for depressed patients resistant to medication?
Mark S. George, MD, a brain imager, psychiatrist, and neurologist at the Medical University of South Carolina, was the first to use rTMS for depression, in the early 1990s. Then at the National Institute of Mental Health, he began by exploring the use of TMS as an experimental tool to study neuronal circuits related to mood. Later, he investigated its use as an antidepressant. By 1993, he had found that daily treatment with TMS over several weeks could treat depression that hadn't responded to medication.
He did the first large NIH study on the technique, showing "clearly, convincingly that it has effects" in the treatment of depression, he says. He found about a 15-20% remission rate in active groups, compared to only 5% in those who received sham treatment. For George, that was good -- but not good enough. "Most people were still sick," he says. "It was kind of disappointing."
One of the subsequent discoveries was that continuing treatment for a longer time produced better results. So did the addition of adjunctive medication. In 2008, largely because of his work, the FDA approved the use of rTMS for depression. The protocol specified that it should be given five times a week, for 6 weeks, with medication.
"When it's used for six weeks and adjunctively, you can get remissions to 30-40%, he says. There have now been about 15 meta-analyses of the data that support its effectiveness, he says. "If you ask psychiatrists who are informed about depression, they will say it's a great tool."
The FDA approved rTMS in 2008, based on experiments George did with a machine from a company called Neuronetics, based in Malvern, Pa. Since then, three more devices have received FDA approval.
rTMS strengthens circuits in the prefrontal cortex in much the same way that weightlifting stimulates and strengthen muscles. A single set of bicep curls does little to build up muscle mass. But continue that for a period of weeks, and those muscles bulk up and get stronger. It's much the same with rTMS. The magnetic field produces currents in neurons in the prefrontal cortex, but daily, repeated applications of the field are necessary to product an effect. Many patients feel little or no change until after a few weeks of treatment. But then their depression often starts to lift, a consequence of a stronger, bulked-up prefrontal cortex. New neurons are being made and new circuits turned on.
The treatment continues to improve. George just completed a trial in which some patients could be maintained as outpatients without medication.
The side effects are minimal. Some patients report a mild headache on the skin near the coil. Others say they feel something like a woodpecker tapping on their foreheads.
Determining whether rTMS is a wise buy requires juggling a number of factors. The treatment itself costs about $200-300 per daily session. That's 3,000-5,000 magnetic pulses over a period of about 20 minutes. Multiply the cost by five sessions a week (with weekends off) for 4 to 6 weeks, and the price tag ranges from about $5,000-$10,000. Patients who need adjunctive medication or psychotherapy will face additional charges. Medication for 6 weeks might cost "a couple of hundred bucks," George says.
ECT costs about twice as much, he says. Patients are anesthetized, so they need an anesthesiologist. Many of these severely ill patients also require hospitalization. And the patients need to be driven home from the treatment. In contrast, patients who receive rTMS can jump in their cars afterwards and drive home themselves.
ECT patients also need a physician's supervision. rTMS needs physician supervision initially, but once a psychiatrist has determined the dose, nurses, or technicians can do the follow-up treatments, George says.
Linda L. Carpenter, MD, a professor of psychiatry and human behavior at Brown University, opened a clinic with a Neuronetics device in 2009 and now has two devices running full time from 7:30 in the morning until 6:30 at night. "Half of the people who come to my clinic have been hospitalized," she says. "Many have had ECT." Some are barely holding on to their jobs and can't check into a hospital.
A course of rTMS costs them $6,000-$12,000 at her clinic. But the savings are significant, too. "We can eliminate hospitalizations," she says. "Our clinic's response rate is 60%." Hospitalization for ECT costs $10,000 to $20,000, she says.
Kit Simpson, a professor of public health at the Medical University of South Carolina, has analyzed the costs of rTMS in terms of QALYs, or quality adjusted life years. In the U.S., the benchmark for whether a treatment is cost effective is whether the cost of a QALY comes in at less than $50,000. For TMS, producing one QALY costs $36,000, according to Simpson's analysis.
"This is a good deal. This is a wise buy," she says. That's true for insurance companies and it's true for patients themselves. They have a good chance of not being depressed.
"A substantial portion of consumers who have health insurance have access to a policy that covers at least a portion of rTMS treatment," says Mark Demitrack, MD, a psychiatrist and the chief medical officer at Neuronetics. "And Medicare covers it in most jurisdictions."
Demitrack estimates that some 30,000 people have been treated with TMS and that about 4 million could benefit from it. "We're at exceedingly small clinical penetration," he says. In contrast, about 100,000 to 150,000 people are treated with ECT each year, he says.
Demitrack won't say what one of his rTMS machines costs, but, he says, "Our intent is to price the technology in a manner in which the costs are appropriate for the practitioner. Our primary customer is the practicing psychiatrist."
George is convinced that the cost of treatment will come down as a result of further research. "What if we could do it so they only had to come half that time, or could come for one day and get well? I've been working from a scientific viewpoint to make it more efficient -- less time in the chair," he says.
Others are looking at the many other conditions that might one day be treated with rTMS or similar brain-stimulation techniques.
Sarah H. Lisanby, MD, a psychiatrist and the director of the Division of Translational Research at the National Institute of Mental Health, is looking at a technique called CTMS, or controllable transcranial magnetic stimulation, in which the shape of the magnetic field can be adjusted, and DTMS, for deep TMS, in which the field penetrates more deeply into the brain. She's also experimenting with its use to create seizures (magnetic seizure therapy or MST), perhaps more safely than is done with ECT.
"We're in the early stages, learning how to optimize the dose of the treatment," she says. "It was approved with a dose that worked to a moderate degree," she says.
She has just completed a study of the use of rTMS with bipolar disorder. (The results have not yet been released.) She's also studying transcranial direct current stimulation, or TDCS, "which is looking very promising" as a treatment for depression, she says. And it's even simpler. "It's a box with a battery in it," she says.
Carpenter says rTMS is now being studied with a variety of disorders, including stroke rehabilitation and Parkinson's disease. She's involved with a trial that synchronizes pulses with a patient's own alpha waves, perhaps to entrain those waves and more quickly restore healthy communication between neurons.
All of which suggests one more possibility: Could rTMS be used one day to enhance brain activity in people who are not sick, but who want a zippier brain?