Transcranial Magnetic Stimulation Gains FDA Clearance

Transcranial magnetic stimulation (TMS), a method of non-invasively stimulating the brain, has just recently gained clearance for the treatment of major depression. This is one of the first FDA clearances of TMS for a brain disorder. TMS has actually been around quite some time (since 1985) and has shown considerable promise for treating a variety of brain disorders. TMS has been used by scientists to deactivate or activate specific regions of the brain's outer layer (the neocortex) by sending multiple magnetic pulses through a person's skull using a TMS device. These magnetic pulses are able to create an electric current in a very targeted brain region. This electric current can then cause either an inhibition or an excitation of the underlying brain tissue depending on which frequency of the TMS pulse that is used. High frequency magnetic pulses are able to excite brain tissue while lower frequency pulses tend to decrease brain activity. So specific brain regions may be selectively activated or deactivated. Brain disorders often have hyperactive or hypoactive activity in specific regions, and TMS is able to selectively adjust this brain activity non-invasively.

I think approval for other conditions will follow after this success. Neuronetics, the company marketing the TMS device, had actually tried in 2007 to get approval but failed quite spectacularly. Neuronetics has previously showed the results from a different TMS trial to a board of several FDA advisors in 2007. For that specific trial, the clinical outcome was measured by a reduction in major depression scores on the Montgomery-Asberg Depression Rating Scale (MADRS) symptom score after undergoing a treatment with TMS for six weeks. Symptoms for major depression include profound sadness, apathy and an inability to experience pleasure.

In that previous trial the TMS failed to distinguish itself from the sham/fake TMS for improving depression symptoms. The mean decrease in the MADRS symptom scores was approximately 5.6 points in the active transcranial magnetic stimulation group of patients and about 3.2 points in the sham/fake TMS group of patients. Unfortunately for the company Neuronetics, the p-value after 6 weeks was just .058. A p-value (see statistics) that is less than .05 is the difference between the active and sham TMS that is considered statistically significant. So the difference between fake and real treatment was just not enough to prove efficacy. Neuronetics had also tried to compare the efficacy of TMS to ECT, which is a bad move. ECT has a much greater mood elevating effect than TMS and they are not comparable. TMS, though, has almost no side effects in comparison to numerous side effects with ECT or antidepressants, which is a huge plus. ECT causes a brain seizure and requires a person to undergo anaesthesia. ECT has a drastic effect on the functioning of the entire brain. TMS on the other hand can be performed on a person while they are totally awake and is fairly painless. So TMS does have advantages to both ECT and antidepressants. Neuronetics had to do another trial in order to get better results and satisfy the FDA. It appears that they were successful in convincing the FDA.

Neuronetics, Inc., a privately-held medical device company and a leader in the field of neuromodulation, announced today that the U.S. Food and Drug Administration (FDA) has cleared its NeuroStar TMS (Transcranial Magnetic Stimulation) Therapy system for the treatment of depression. NeuroStar TMS Therapy® is specifically 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. In clinical trials with NeuroStar TMS Therapy, these patients had been treated with a median of 4 medication treatment attempts, one of which achieved criteria for adequate dose and duration.

You can read the data from the clinical trial at this website. The success from the new trial seems to be partially due to "adjusting" the outcome parameters a little. Notice that the end point this time was 4 weeks and not 6 weeks. However, it is possible that they amped up the amount of TMS excitation that the patients received as well for a better effect.

The primary efficacy measure, the Montgomery-Asberg Depression Rating Scale (MADRS) symptom score change at 4 weeks, was statistically significantly superior to placebo (p=0.0006), among NeuroStar-treated patients. Similar results were observed with the Hamilton Depression Rating Scale (HAMD). NeuroStar TMS Therapy-treated patients had statistically significant response and remission rates, which were approximately twice the rate of placebo-treated patients. The response rate is the percentage of patients who had a greater than or equal to 50% improvement in symptoms, and the remission rate is the percentage of patients who achieved virtually complete symptom resolution. NeuroStar TMS Therapy also produced statistically significant improvements on the HAMD factor scores for core depression symptoms, anxiety symptoms, somatization, and psychomotor retardation.

In the future, neuronetics will probably get competition from brainsway, the company making the deep transcranial magnetic stimulation device. This recent Neuronetics TMS trial only targeted the left dorsolateral prefrontal cortex, but researchers may also be able to target the right dorsolateral prefrontal to gain an even greater antidepressant response. So I think this treatment will end up getting better as scientists are able to target more brain areas for activation/deactivation. I suspect Neuronetics had to do a lot of data manipulation to get the right outcome for this recent trial. However, TMS may still become more useful for brain disorders as time goes on.