Depression: The Current Approach
Transcranial magnetic stimulation was 'a magical curiosity' when it was first used to study the human motor system. Now, some scientists regard it as a promising new treatment for patients who don't respond to antidepressants.
The Bethesda woman had tried pretty much every depression treatment out there.
She suffered postpartum depression after the birth of her first child 35 years ago. With a baby at home, she wanted a quick fix and opted for electroconvulsive—aka “shock”—therapy (ECT) and medication. She felt better at first, but her depression returned many times over the decades. Then, after one of her grown children died several years ago, no medication could relieve her despair.
Her psychiatrist suggested the newest treatment on the market: transcranial magnetic stimulation, or TMS. In 2011, she decided to try it.
A noninvasive, outpatient procedure that appears to have fewer side effects than antidepressants, TMS has been shown in studies to help three or four out of every 10 patients who previously received no relief from medication. It’s expensive—amounting to more than $10,000 in the woman’s case, and not covered by her insurance—as well as time-consuming.
The Bethesda woman had to drive to Dr. Wagdi Attia’s Gaithersburg office in afternoon rush-hour traffic five days a week for six weeks. Once there, she sat in a chair and a coil that emitted electromagnetic pulses was placed on her scalp near an area of the brain believed to play a role in mood regulation. The pulses, comparable to those generated by MRI machines, induced small electric currents in her brain. Less than an hour later, she drove home.
“You get to a point where you’re desperate,” says the woman, who asked not to be identified. “Somebody is offering you a lifeline, you do it.”
Transcranial magnetic stimulation didn’t start out as a treatment for depression. Scientists in England and the United States began using it in the 1980s as a laboratory tool for studying the physiology of the human motor system. Depending on where the TMS coil was placed on the scalp, “you could disrupt ongoing activity like speech,” explains Dr. Eric Wassermann, a Bethesda resident who’s on staff at the Behavioral Neurology Unit, Division of Intramural Research at the National
Institutes of Health’s National Institute of Neurological Disorders and Stroke.
In those early days, TMS was “almost a magical curiosity,” Wassermann writes in a 2012 article in the journal Pharmacology & Therapeutics.
Dr. Mark George, a psychiatrist who was formerly a fellow at the National Institute of Mental Health (NIMH), part of NIH, wondered in the early 1990s whether TMS might be useful in treating depression.
“Way back then we thought there might be a ‘there’ there,” says George, who has been on the faculty of the Medical University of South Carolina in Charleston since his NIMH fellowship ended in 1994.
Using PET scans, an imaging tool that helps show how organs are functioning, George observed that the frontal cortex of depressed patients’ brains—particularly the left side—wasn’t as metabolically active as in healthy individuals. Perhaps targeting that part of the brain with TMS could rev up metabolism and lift depression, he thought, in the same way ECT effectively treats the illness by passing electric currents through the brain.
Of course, ECT is administered under anesthesia and uses more intense currents that cause a brief seizure. Many scientists and doctors assumed that the seizure itself played a key role in improving patients’ moods. Nonetheless, George and Wassermann decided to test TMS in six depressed patients for whom antidepressants hadn’t worked. They reported the results in 1995: Two patients experienced a marked improvement after receiving TMS for several days. Two experienced slight improvement, and two didn’t improve at all.
George went on to lead the first multisite, randomized TMS trial ever conducted without the involvement of a company interested in marketing the treatment. The NIMH-funded study randomly assigned 190 patients with major depressive disorder who weren’t taking antidepressants to one of two treatment groups. One group received TMS for 37½ minutes daily, Monday through Friday, for three weeks. The other group received sham TMS with a metal insert blocking the device’s magnetic field. Neither the researchers nor the patients knew who was in which group.
About 14 percent of the patients who received TMS experienced a remission of their depression, compared with about 5 percent of those who got the sham therapy, George’s team reported in 2010 in the Archives of General Psychiatry. The remission rate more than doubled to nearly 30 percent among patients who opted to continue in the study’s second phase, where everyone received TMS.
The NIMH-funded trial confirmed the results of a study conducted by Neuronetics, a Malvern, Pa., company whose NeuroStar system in 2008 was the first—and, until this past year, the only—TMS device to be cleared by the Food and Drug Administration. The agency OK’d the device only for the treatment of medication-resistant depression in adults.