Adults who suffer from depression may be able to try a new type of therapy, transcranial magnetic stimulation (TMS), when antidepressant medication fails to work. Neuronetics (Malvern, Pennsylvania), a private device company, said the FDA has cleared its NeuroStar TMS system for the treatment of depression.

Mark Demitrack, MD, chief medical officer at Neuronetics, told Medical Device Daily that there were two primary driving factors behind the development of the NeuroStar system.

"One is, quite frankly, the fact that major depression is an illness that remains substantially underserved," Demitrack said.

Most patients treated with pharmaceutical antidepressants don't get better, Demitrack said. In fact, he added, only one in three patients treated with pharmaceutical antidepressants do get better. He said side effects and intolerability is a big reason why these drugs don't work for many patients, while a significant number don't work simply because they don't work.

"Usually what the doctor will do is attempt to mix and match treatments, it's a trial and error, often months will elapse and a patient is still in middle of an illness," Demitrack said.

Another major driving force behind the development of NeuroStar, he said, is the fact that the therapy is noninvasive (no surgery required) and non-systemic meaning it doesn't circulate the blood so patients don't experience the array of side effects that often accompany pharmaceutical antidepressants, such as weight gain and sexual dysfunction.

The NeuroStar system consists of power electronics, a touch-screen control panel, an electromagnetic coil, a single-use treatment link that is placed between the coil and the patient's scalp, and a treatment chair that looks a lot like a dentist's chair. During a treatment session the TMS coil is placed over the patient's left pre-frontal cortex an area of the brain involved in mood regulation and repeatedly energized. Each time the coil is energized an MRI-strength magnetic pulse enters the cortex and briefly introduces an electric current to flow, according to Neuronetics.

The treatment, prescribed by a psychiatrist, is usually administered daily for four to six weeks in a psychiatrist's office. Each treatment session lasts about 40 minutes, the company noted.

The NeuroStar system is indicated for the treatment of major depressive disorder in adult patients who have failed to achieve satisfactory improvement from one prior antidepressant medication at or above the minimal effective dose and duration in the current episode.

"Depression is a debilitating illness, and existing treatment options are frequently ineffective or intolerable due to side effects," said Bruce Shook, president/CEO of Neuronetics. "The availability of NeuroStar TMS therapy means that patients suffering from this disease now have an entirely new non-systemic and non-invasive treatment option that has been proven safe and effective."

Demitrack said Neuronetics began its clinical trial in early 2004, completed the trial in 2005, and submitted the data to the FDA in 2006. But getting the system cleared was easier said than done, as is often the case with the U.S. regulatory process.

Early in 2007 an FDA advisory panel, without formally voting, gave the device a thumbs-down, questioning among other things the fact that the company filed the application with electro-convulsive therapy (ETC) serving as the predicate device (Medical Device Daily, Jan. 30, 2007).

"ETC is not an appropriate predicate device for TMS because TMS is so strikingly different," Demitrack said.

The panel also recommended to the agency and the company that it dive deeper into its clinical data to determine which subset of patients benefit most from the therapy, which led to the device being indicated for patients with major depressive disorder who have failed to benefit from one prior antidepressant treatment in their current episode.

"In that patient population, the outcome really is remarkable," Demitrack said.

The company resubmitted the data to the FDA about a year ago, Demitrack said, which is what led to the recent clearance of the TMS system. While the advisory panel that examined the device last year raised many questions about the therapy, he noted that there was never any doubt about the safety of it.

"Clinical neuroscience advances have greatly improved the diagnosis and treatment of depression, but much more is needed. These disorders lead the world in producing disability, and more than half of the millions being treated for clinical depression currently fail to achieve wellness," said John Greden, MD, professor of psychiatry and clinical neurosciences and executive director of the University of Michigan Comprehensive Depression Center (Ann Arbor). "Before now, few options have been available for them other than complex and often unproven combinations of medications. Now, with the FDA clearance of NeuroStar TMS therapy, there is new hope."

According to the company, a six-week, randomized, placebo-controlled, double-blind, study was conducted to evaluate the safe and effective use of NeuroStar TMS as a monotherapy. The study population was comprised of 164 patients with unipolar, non-psychotic major depressive disorder. Almost all of them (97%) had suffered previous depression episodes, the company noted.

These patients also had an extensive treatment history without a satisfactory improvement. They had received a median of four total prior antidepressant treatment attempts in the current episode, one of which achieved treatment adequacy at or above the minimal effective dose and duration. Some 48% were unemployed due to their depression, 35% had a co-morbid anxiety disorder, and all had moderate-to-severe depressive symptoms, Neuronetics said.

"In the randomized controlled trial conducted for FDA clearance, NeuroStar TMS therapy demonstrated statistically and clinically significant treatment effects," said Phil Janicak, MD, professor of psychiatry at Rush University-Chicago and a principal investigator in the NeuroStar TMS therapy clinical trials.