Transcranial magnetic stimulation is gaining ground as a therapy for treatment-resistant depression.
Sharon Gray* has had depression for most of her life. She was first diagnosed at 30, but she believes her depression started much earlier. Now 61, the retired police lieutenant from Columbus, Ohio, has seen clinical psychologists and psychiatrists and taken antidepressant medication for most of the last three decades. The treatments have left her functional, she says, but still mildly depressed. Every so often, she’s suffered periods of more severe depression.
In 2007, desperate for a new option, she flew to Atlanta for a therapy that, at the time, was still experimental: transcranial magnetic stimulation, or TMS. Just past the halfway point in the monthlong course of treatment, “I had what I thought were miraculous improvements,” Gray says. “I went to sleep on a Tuesday night depressed, and woke up Wednesday morning not depressed.”
To celebrate, she went jewelry shopping. If that sounds trivial, think again: “I had not been interested in my appearance for so long,” she says.
The following year, in 2008, the Food and Drug Administration (FDA) approved TMS as a treatment for people with major depression who have failed to respond to at least one antidepressant. Initially, the agency approved just one TMS device, called NeuroStar, made by the company Neuronetics. In 2013, the FDA approved a second device, manufactured by Brainsway.
In the years since FDA sanctioned the therapy, TMS treatment centers have been popping up across the country. Slowly, insurance companies have begun to cover the non-invasive, though costly, treatments. But plenty of questions about TMS still linger, including how best to deliver it, which patients make the best candidates and even what, exactly, the device is doing in the brain.
Despite that, the therapy is gaining support from patients and mental health providers alike. “I think it’s a promising treatment,” says William McDonald, MD, a psychiatrist at Emory University School of Medicine who was involved in the clinical trials that led to the approval of the NeuroStar device. “I’m a skeptic. But if I had significant depression and I had failed one or two antidepressants, I’d have to consider TMS.”
Changing neural networks
TMS is typically administered by a physician or a nurse. The procedure involves a non-invasive machine placed against the scalp. The device sends short but intense magnetic pulses into the brain, where they generate an electric current. The pulses are centered over the left prefrontal cortex, an area that often shows abnormal electrical activity in depressed patients. A typical course of TMS therapy involves 20 to 30 sessions, generally given in three to five treatments per week for four to six weeks. The full course of therapy with the pricey machines can cost $6,000 to $12,000. During the treatments, patients remain awake and alert, seated in a chair while a physician or a nurse places the device against the scalp.
TMS has become a promising treatment alternative for the estimated 30 percent to 50 percent of people with depression who don’t respond sufficiently to antidepressant medications. One option commonly offered to such patients is electroconvulsive therapy (ECT), a procedure in which electrical currents are sent through the brain to trigger a short seizure. ECT has been available in the United States for more than 70 years. Administered several times per week over three to four weeks, ECT can be effective at alleviating major depressive disorder.
However, ECT has some significant drawbacks. It can cause confusion and memory loss. Plus, it must be administered under anesthesia, which comes with risks of its own and adds preparation and recovery time to each session.
Gray had tried ECT, but her doctor discontinued the treatment after she experienced serious memory loss. “I have no recollection of that entire two-plus weeks,” she says. “I live alone, and it was scary.”
TMS, by contrast, is administered while patients are awake. “You sit in a chair, it takes about 30 minutes, and then you can get up and drive yourself home,” says McDonald. Side effects are minimal; headache and muscle soreness are the most common complaints. Though there is a small risk of seizure, it’s reportedly comparable to the seizure risk associated with antidepressant medications. Compared to ECT, Gray says, “TMS is a walk in the park.”
But like antidepressant medication and ECT, it’s not entirely clear how TMS is acting on the brain. “The theory is that when this stimulation occurs in the left frontal brain, it spreads to the underlying deeper areas of the brain that are involved in regulation of mood. When we do it over and over again, it normalizes the neuronal circuits involved in depression,” says Ananda Pandurangi, MD, a psychiatrist at the Virginia Commonwealth University School of Medicine.
Like ECT, TMS appears to reset the system. But instead of jump-starting the entire brain, as ECT does, the magnetic therapy is much more targeted, says Megan Schabbing, MD, a psychiatrist at OhioHealth Riverside Methodist Hospital who treated Gray with TMS. “That’s undoubtedly why it’s so well tolerated,” she says, “but this treatment provides a novel approach to the transformation of neural networks.”
Everything’s a question
While TMS shows promise, it’s certainly no miracle cure. Some of the patients who responded positively to TMS have experienced remissions lasting months or even years, but follow-up booster sessions every few weeks or months may help prevent a relapse.
About six months after her incredible improvement in 2007, Gray says, her depression began to resurface. She underwent a second course, this time at a clinic in Vancouver, Canada. While she felt better, her improvement was more modest the second time around.
Gray had paid out of pocket for the pricey therapy and was quickly burning through her retirement savings. She couldn’t afford another round, even after her depression resurfaced months later. “So I puttered along until a few years ago, when I had another deep depression,” she says.
By then the treatment had been approved by the FDA. Still, it took Gray multiple applications over several years before her insurance company agreed to cover the treatment. She finally underwent a third course of TMS in 2014. “I feel pretty good,” she says. “I’ve had two pretty bad pieces of news in the last couple weeks and I didn’t crumble.”
Now Gray is planning to have a maintenance course of TMS every month or so, in hopes that it will keep her depression at bay. She’s still not sure if her insurance will pay for those booster sessions — and that’s not the only thing that remains unclear about maintenance TMS.
French researchers recently reported that patients who received maintenance TMS were significantly less likely to relapse than those who did not receive boosters (Journal of Affective Disorders, 2013). But the study was small, and the best way to administer such treatments is far from settled. “The protocols for maintenance boosters don’t exist. Nothing has been approved by the FDA, so we devise our own protocols,” Pandurangi says.
In fact, he adds, when it comes to TMS, “almost everything is a question.” What’s the best frequency and intensity of the magnetic pulse? How many total treatments should patients receive, over how many days or weeks? Where on the scalp should the current be directed?
Researchers are a long way from fine-tuning the technique, George agrees. “All the things we did in the first studies used a good first approximation, and it turned out that it worked,” he says. “However, it would be inconceivable that the first approximations were also the best approximations.”
There’s some evidence the total amount of brain stimulation is what matters, rather than the number of calendar days spent in treatment, George says. In a recent pilot study, George and his colleagues tested TMS as a treatment for patients hospitalized during a suicidal crisis. Patients received nine TMS treatments in just three days. They experienced no serious side effects from the rapid-fire course of treatment, George says, and those who received TMS showed more improvements on the first day than did control subjects who received a sham treatment (Brain Stimulation, 2014).
“They got unsuicidal very quickly,” George says — though he acknowledges that more research and larger samples are required to fully test the approach.
While many questions remain, scientists who study the device say it’s a valuable tool for psychologists to keep in mind when referring patients with difficult-to-treat depression. “Psychologists should know it’s a good treatment option for patients who have failed to respond to or tolerate antidepressant medication,” Schabbing says.