15 October 2008—Neuronetics, a medical-device firm in Malvern, Pa., has won approval from the U.S. Food and Drug Administration (FDA) to market its repetitive transcranial magnetic stimulation (rTMS) therapy for treatment of depression in the United States. The device delivers tightly focused pulses of an MRI-strength magnetic field through the skull to produce current within a small portion of a person’s brain. At the end of Neuronetics’ clinical trial of patients with depression who had not responded to at least one drug therapy, one in two showed a significant improvement, and one in three were practically depression free. Neuronetics’ NeuroStar system is one of only three device-based psychiatric treatments that can be marketed in the United States.
Depression affects at least 14 million adults in the United States each year, but nearly 30 percent of patients with depression do not benefit from or are unable to tolerate antidepressant drug therapy. Device-based therapies such as rTMS are intended to treat those patients for whom drugs haven’t worked.
Neuronetics’ transcranial magnetic stimulation device is, at its heart, a big capacitor that discharges thousands of amperes per pulse into the coil of an electromagnet, which generates the magnetic field. The coil is maneuvered to a spot on the patient’s head where the magnetic pulse will penetrate a region of the brain above and behind the eyes that has been linked to depression. Patients need no anesthesia or sedation during the 40-minute outpatient procedure, and they are usually treated daily for four to six weeks.
The decision by the FDA comes more than a year after the clinical results of the device were met with strong skepticism by the agency’s advisory panel. Under FDA rules, Neuronetics had to prove that the risk-to-benefit ratio for their rTMS technology was equivalent to that of a technology already in use, in this case electroconvulsive therapy. Electroshock carries a number of risks, not the least of which is memory loss, but it’s also highly effective. In fact, it’s the go-to treatment to snap patients out of serious depression when other treatments fail.
In the Neuronetics trial, and indeed in the dozens of trials using rTMS, the risk was very small. However, the company had a hard time proving that the benefit was real without statistical maneuvers, including the removal of several patients from the data set, which seemed to put off the FDA’s advisers.
Neuronetics spent months consulting with the FDA about its data. The turning point may have come when the rTMS trial results were published in the prestigious World Journal of Biological Psychiatry , and the statistics behind them were generally accepted by the academic community, suggests Dr. Mark S. George, the psychiatrist and neurologist who pioneered rTMS in psychiatry and an unpaid adviser to Neuronetics.
Neuronetics’ stimulator now becomes only the second psychiatric device to go through the agency’s approval process, which is one of the toughest in the world. Vagus nerve stimulation (VNS), a therapy used for years to treat epilepsy by implanting a pacemaker-like device to electrically stimulate a nerve in the neck, was initially rejected by the FDA. But after months of consultation with Cyberonics, the stimulator’s maker, the regulator reversed course. (Electroconvulsive therapy predates the FDA’s governance over medical devices, so it never had to go through an approval process.)
Despite its approval, rTMS still faces some hurdles. Insurers balked at paying for VNS, which requires surgery and can cost $25 000, greatly reducing the market for the therapy and damaging Cyberonics’ business. George suspects that insurers will be willing to pay for rTMS, for two main reasons. First, the base of evidence supporting rTMS—several dozen trials have been performed using Neuronetics’ and other stimulators—is much larger than that of the single Cyberonics-funded VNS trial. Second, rTMS doesn’t have VNS’s high upfront costs. ”Insurers could agree to pay for a few weeks [of rTMS] to see if it’s working,” then decide whether or not to continue treatment, says George.
Even with an rTMS device approved, there is still a lot of fundamental research to be done on how the therapy works, why it works for some and not others, and how to make it work better. ”This is but one baby step in a long process,” says George, who is director of the brain stimulation laboratory at the Medical University of South Carolina. ”But it’s an important one.” New electromagnetic coil technology will allow doctors to stimulate a smaller portion of the brain or to electrify areas deeper within the organ. Where the electromagnet is placed on the head, how long a treatment session lasts, how frequently it is delivered, and other aspects of the treatment are also in need of refinement. Those parameters ”are from some early assumptions I made in 1993, and many of those are unexamined,” says George.