The Food and Drug Administration (FDA) has cleared the first transcranial
magnetic stimulation (TMS) device for treatment of medication-resistant
depression, the device manufacturer Neuronetics Inc. announced last month.
The device, known as NeuroStar TMS Therapy system, is indicated as a daily
monotherapy for adults with major depressive disorder who have failed to
respond to at least one course of antidepressant treatment with an adequate
dosage and duration.
The device works by applying repeated, high-frequency magnetic pulses at a
specific location outside the cranium to provoke electrical currents inside
the patient's brain, thus activating the neurons in the prefrontal cortex.
The procedure, which is noninvasive and painless, is conducted in the
outpatient setting. Unlike electroconvulsive therapy (ECT), patients need no
anesthesia or sedation. The patient remains awake and alert during a 40-minute
session of stimulation, in which the device delivers 3,000 pulses per
In a randomized, sham-controlled, double-blind clinical trial of the TMS
device conducted from January 2004 to August 2005, more than 300 patients with
major depression who had failed previous pharmacotherapy were randomized to
receive either active or sham stimulation every day for six weeks. Patients in
the study had previously failed a median of four courses of antidepressant
The TMS treatment was shown to be significantly more effective than sham
stimulation in reducing depressive symptoms at weeks 4 and 6 as measured by
the Montgomery-Asberg Depression Rating and Hamilton Depression Rating scales.
Clinical trial results were published in the December 1, 2007, Biological
Psychiatry by John O'Reardon, M.D., and colleagues.
Some of the patients in the randomized clinical trial continued with
active, open-label treatment for up to 24 weeks. Relatively few adverse
effects were reported. The most common treatment-related adverse events were
headaches and scalp pain or discomfort, which were transient and mild to
moderate in severity. There were no deaths or seizures, according to a summary
of the safety data from these trials published in the February Journal of
Clinical Psychiatry by Philip Janicak, M.D., and colleagues. No memory
loss or cognitive changes were seen in patients in the trials. Less than 5
percent of the study sample discontinued treatment because of adverse
One serious adverse event reported in the trials was left-sided facial
numbness in one patient, which was related to irritation of the trigeminal
nerve. The event resolved after the treatment was discontinued. First-degree
burns in two patients and severe pain at the treatment site in one patient,
all due to device malfunction, occurred in the first trial.
"Those early events in the clinical trial were caused by a technical
issue with a prototype of the device," Mark Demitrack, M.D., the medical
director of Neuronetics, told Psychiatric News. The problem was
remedied in the redesigned commercial version of the device and did not occur
again in the clinical trials.
The device stimulates a specific area of the brain—the left
dorsolateral prefrontal cortex. The stimulation over time, however, is likely
to lead to beneficial changes in other regions involved in depression, Sarah
Lisanby, M.D., chief of the Columbia Brain Stimulation and Therapeutic
Modulation Division, told Psychiatric News. Lisanby, a professor of
clinical psychiatry at Columbia University and the New York State Psychiatric
Institute, was one of the investigators involved in the Neuronetics trials of
the device. She is also the chair of APA's Task Force to Revise the Practice
of Electroconvulsive Therapy.
"One of the goals of studying TMS has been to see if it can offer
help for patients when medications fail and to find out where it may fit into
the overall treatment for depression," she said, noting that TMS is not
invasive and has fewer cognitive side effects than ECT and thus may present a
second option after pharmacotherapy, but before initiating ECT.
In January 2007, an advisory panel told the FDA that the device is safe,
but that its efficacy may not be "substantially equivalent" to
ECT. Thus it was not approved for a premarket 510(K) notification sought by
the company. 501(K) is an accelerated market-approval process in which the
applicant needs only to prove that a device is "substantially
equivalent" to another marketed device in safety and efficacy. Thus the
FDA had requested additional analyses of the clinical trial data and issued
the clearance nearly two years later.
TMS treatment is "vastly different from ECT," said Demitrack.
He emphasized that the appropriate indication for the device is for use in
patients who have failed a course of drug therapy with an adequate dose and
duration, which is not the same as the first antidepressant drug tried
unsuccessfully by a patient. Because of tolerability problems, many patients
have to try several antidepressant drugs for months before completing one
course of pharmacotherapy at minimum effective dose and duration, he
In a study published August 13 in Neuropsychopharmacology online,
Lisanby and colleagues analyzed the clinical trial data and found that
patients who had failed one adequate course of antidepressant treatment
responded significantly better than those who had failed multiple courses of
full-dose, f ull-duration antidepressant treatment.
The TMS device will be available at a limited number of treatment centers
at first, but its availablity will be expanded in the next year, according to
the company's announcement.
An abstract of "Efficacy and Safety of Transcranial Magnetic
Stimulation in the Acute Treatment of Major Depression: A Multisite Randomized
Controlled Trial" is posted at<www.journals.elsevierhealth.com/periodicals/bps/article/S0006-3223(07)00146-1/abstract>.
An abstract of "Transcranial Magnetic Stimulation in the
Treatment of Major Depressive Disorder: A Comprehensive Summary of Safety
Experience From Acute Exposure, Extended Exposure, and During Reintroduction
Treatment" is posted at<www.psychiatrist.com/abstracts/abstracts.asp?abstract=200802/020807.htm>.
An abstract of "Daily Left Prefrontal Repetitive Transcranial
Magnetic Stimulation in the Acute Treatment of Major Depression: Clinical
Predictors of Outcome in a Multisite, Randomized Controlled Clinical
Trial" is posted at<www.nature.com/npp/journal/vaop/ncurrent/abs/npp2008118a.html>.▪