Treatment of severe depression with magnetic stimulation is moving beyond large mental health centers and into private practices nationwide, following more than two decades of research on the treatment. Yet even as concern about its efficacy fades, one potential side effect—seizures—continues to shadow the technology.



Called repetitive transcranial magnetic stimulation (rTMS), the noninvasive technique uses electromagnets to create localized electrical currents in the brain. The gentle jolts activate certain neurons, reducing symptoms in some patients. Eight psychiatrists contacted for this article, all of whom use rTMS to treat depression, say it is the most significant development in the field since the advent of antidepressant medications. The prevailing theory is that people with depression do not produce enough of certain neurotransmitters, which include serotonin and dopamine. Electricity (administered in combination with antidepressants) stimulates production of those neurotransmitters.



Scope of the problem

A National Institute of Mental Health (NIMH) study released this spring shows that 14 percent of patients with drug-resistant major depressive disorder experience a remission of symptoms after rTMS treatment compared with a control group, which reported a 5 percent rate of remission. Physicians and researchers say those results are similar to the success rate of antidepressants. No notable side effects occurred during the study, according to its authors, who include Mark George, an early rTMS researcher and a professor of psychiatry, radiology and neurosciences at the Medical University of South Carolina in Charleston. They have suggested that higher levels of electrical stimulation might attain better results.



At the heart of this interest in rTMS treatment is the only such device cleared by the U.S. Food and Drug Administration (FDA). In October 2008 the government specified that Neuronetics, Inc.'s NeuroStar could be used to treat major depressive disorder that is resistant to at least one antidepressant medication. Since then, about 200 centers and clinics in the U.S. have purchased the $60,000 system, which resembles a contemporary dentist's chair with an electronics console.



The treatment joins talk, pharmaceutical and electroconvulsive therapies (the latter of which rTMS is an offshoot) as the only known methods of alleviating the debilitating symptoms of depression. Nearly 7 percent of U.S. adults, or 14.8 million people (predominantly women), are afflicted by major depressive disorder each year, according to the NIMH. In fact, the NIMH says the disorder is the leading cause of disability in the U.S. for people aged 15 to 44. George says that about half of all patients suffering from serious depression resist at least one antidepressant.



Changing brain chemistry

Unlike with electroconvulsive, or electroshock, therapy, where patients must be unconscious and administered muscle relaxants in order to prevent seizures, patients receiving rTMS (which involves trains of pulses during each session, hence the "repetitive" modifier) remain conscious and seated in outpatient settings. Highly focused magnetic pulses of up to 1.5 teslas induce an electrical current two to three centimeters deep in the left prefrontal section of the cerebral cortex. That region, which acts as an emotion modulator, appears to be underproducing neurotransmitters in depression sufferers. The rTMS pulses directly stimulate an area about the size of a quarter, although scientists are examining whether they affect other parts of the brain, too.



As with antidepressants, the electricity likely is changing the brain's chemistry, says rTMS pioneer Eric Wassermann, chief of the Brain Stimulation Unit at the National Institute of Neurological Disorders and Stroke in Bethesda, Md. He was among the first U.S. researchers to investigate rTMS as a way to alter mood.



Treatments typically occur five days a week for four to six weeks. FDA guidelines for first-time NeuroStar treatments call for 3,000 magnetic pulses delivered over 37.5 minutes (a rate considered low-frequency) by a C-shaped ferromagnetic coil held to the patient's scalp.*



*Correction (9/10/10): This sentence was edited after posting. It originally stated that the NeuroStar TMS Therapy System uses a figure 8–shaped magnetic coil.



Worries over seizures

The most common side effects of rTMS include transient headache, scalp discomfort and the sensation that something is tapping on the patient's head in time with pulses during sessions. (In contrast, electroshock, which even Neuronetics says is more effective than rTMS, could cause memory problems and diminished mental acuity.)



The side effect that draws the most concern is rare but serious: grand mal seizures. They trigger loss of consciousness and violent muscle contractions. "Seizures do occur, and they should not be brushed off," George says. The rate of seizures is on par with medication therapy, but hard data is difficult to find, he says, adding that no organization tallies these events globally. A show-of-hands survey during an rTMS conference in Italy this year indicated that some are underreporting seizures, according to George, a vocal proponent of rTMS. Still, he estimates that there have been fewer than 50 rTMS-initiated seizures worldwide since the mid-1980s.



Risks can be reduced by carefully vetting rTMS candidates according to the FDA-approved guidelines, says Jon Nilsen, who operates a NeuroStar at the McGrath Clinic in Orland Park, Ill. Nilsen also acknowledges that patients on antidepressants, which themselves carry a risk of seizure, as well as those with a history of seizures are more likely to have an rTMS-related event.



Wassermann says that overly cautious doctors and entrepreneurs are holding back the development of rTMS for depression. He was among the researchers who created laboratory guidelines in 1998 for applying rTMS—guidelines that he says were "cautious" in regard to minimizing the chance of seizures. Those protocols, he says have gone largely unexamined.



"It's asking a lot of a box that you plug into the wall to change your brain and your life" without hobbling its further development with timidity, Wassermann says.



Insuring treatment

It also asks a lot of people's pocketbooks. The McGrath Clinic charges a discounted rate of $265 per single-day session without insurance, Nilsen says, but it charges $300 to $350 per session if health insurance firms reimburse for treatments. Because insurance coverage for rTMS is spotty, some psychiatrists say they sometimes treat severely impacted patients for free.



As of August 3 Aetna health insurance refused to reimburse for rTMS, which it considers "experimental and investigational". Michigan's Priority Health Insurance Co. covers the initial six-week treatment. Priority, however, does not cover "maintenance" sessions used to prolong remissions and treat relapses, saying the efficacy of these regimens has not been proved.



Psychiatrist Denise Lin says the benefits she has seen in some of her severely depressed patients outweigh the risk of seizure. Lin, founder of Advanced Psychiatric Care of Santa Barbara, Calif., bought a NeuroStar in January.



All five people she has treated with rTMS have reported at least some improvement, Lin says. One patient had been assessed before trying rTMS as very severely depressed based on the widely used Hamilton Depression Rating Scale (HAM-D), a series of multiple-choice questionnaires that clinicians use to rate depression severity. After a six-week course the patient was judged to be in remission and rated "normal" on the HAM-D scale, Lin says.