Posted by ttee on January 27, 2007, at 14:16:39
I was a subject in the Neuronetics Clinical Trial for rTMS and I am not at all surprised that the FDA advisory committee was not impressed. Although, I feared that they were going to just approve it anyway, since it doesn't appear to cause any harm, other than to the pocket book. Back to the drawing board on this one.
Repetitive TMS: Depression Indication Sought
By Richard A. Sherer, Psychiatric Times
URL: http://www.psychiatrictimes.com/article/showArticle.jhtml?articleId=192202875August 2006, Vol. XXIII, No. 9
Twenty-one years after its first application, transcranial magnetic stimulation (TMS) has become a hot topic in the expanding field of device-based treatment modalities.
For 70 years, electroconvulsive therapy (ECT) has been the sole devicebased intervention in common use in American psychiatric practice. Last year, it was joined by vagus nerve stimulation (VNS) as part of the emerging field of neuromodulation, as some of its adherents are calling it. TMS is seen as having advantages over both: unlike VNS, which requires a surgical implant, TMS is noninvasive; in addition, it is more focused and directed than ECT.
At press time, an application to certify repetitive TMS (rTMS) as a treatment for depression was pending with the FDA. FDA officials declined to comment on the review process, but advocates of rTMS are hoping to hear from the agency quickly. Meanwhile, according to an article in the Wall Street Journal in June, patients are going to Canada to receive rTMS treatments.
“We should know by the end of the year,” according to John P. O'Reardon, MD, director of the Laboratory for Transcranial Magnetic Stimulation in the department of psychiatry at the University of Pennsylvania. “It's already available in other countries,” he told Psychiatric Times in an interview. “There are a couple of private clinics in Canada, some in Australia and Israel, and Europe. We're hoping the United States will get to join the club.”
“Basically, the literature is supportive of the antidepressant effects of TMS in a clinical trial,” said Sarah H. Lisanby, MD, director of the Magnetic Brain Stimulation Laboratory, department of biological psychiatry, at the New York State Psychiatric Institute and associate professor of clinical psychiatry at Columbia University College of Physicians and Surgeons. “If TMS wins FDA approval, I believe the medical literature supports the appropriate use of rTMS in selected individuals. It shows great promise in an area where we need more treatment options.”
“The beauty of TMS is that it can be done in a doctor's office. A nurse can do it. Unlike ECT, it requires no general anesthesia. The side-effect profile is better than for an SSRI, and you do not need a neurosurgeon, as you would with VNS,” O'Reardon said.
In May, O'Reardon presented findings from a multicenter randomized controlled trial at the American Psychiatric Association meeting in Toronto. Based on a 301-patient sample from clinics in Australia, the United States, and Canada, the study compared patients receiving TMS treatment with those undergoing a placebo procedure. All of the patients had failed to respond to an antidepressant medication during the current episode of depression.
“TMS was administered in patients who were resistant to a previous round of antidepressant treatment. It was administered as a stand-alone procedure. The TMS was applied to the left pre-frontal cortex in daily sessions in a randomized, double-blind study to compare the active treatment versus a sham treatment. In the sham treatment, the magnetic stimulation doesn't get beyond the scalp. Patients could have received anything from 4 to 6 weeks of TMS in the double-blind phase. After 4 weeks, if patients felt they had no improvement, they could ask to exit the study. If the patients were doing okay, they were encouraged to stay in for the full 6 weeks.”
At the end of the 6 weeks, patients who remained in the study were referred to an open-label study for 2 more weeks. Following that, patients were enrolled in a 6-month maintenance study, in which they used 1 antidepressant medication and had TMS available as a backup.
“The patient group in the maintenance study was composed of 4 populations, 3 of which had responded to active TMS, and the fourth being patients who responded to the sham treatment.”
Patients were evaluated on the Hamilton 17- and 24-symptom scales and Montgomery Asberg Depression Rating Scale (MADRAS). According to O'Reardon, “The response rates in the 2 versions of the Hamilton Scale were significantly higher with active TMS at 4 weeks. Remission was higher at week 6.”
On all 3 scales, patients receiving active TMS showed at least twice the response rate of patients receiving the sham treatment.
At 4 weeks, 20.6% of patients who received TMS showed an improvement of at least 50% on the 17-item Hamilton scale, compared with 11.6% of the patients in the sham group. On the MADRAS scale, a 50% improvement was seen in 18.1% of patients receiving active TMS, compared with 11% of the patients receiving sham treatment.
The remission rate, which O'Reardon defined as a score of 7 or less on the Hamilton scales, was almost the same in the active and sham groups at 4 weeks, but at 6 weeks it showed a dramatic change. Patients in the sham group showed a remission rate of 8.2% on the Hamilton 24-item scale, compared with 17.4% for patients receiving active TMS.
O'Reardon noted that the results were based on a monotherapy and that patients in a clinical setting would be able to receive TMS in combination with another therapy. “During the open-label portion of the study, the response rate was 42% and the remission rate was 20%,” he said. “The company that sponsored the test would argue that the openlabel TMS phase is closer to actual clinical practice.” The study was underwritten by Neuronetics, Inc, 1 of 4 companies manufacturing and marketing TMS equipment.
He said the long-range effectiveness of TMS appeared to be significant in the study as well. “For folks in the maintenance study, if they previously responded to active TMS, two thirds did not need TMS again over the 6 months of the study. Of the one third that did need TMS during that period, two thirds of them responded again. If you went into the maintenance study, you had a 75% chance of surviving without a relapse.”
In addition, he pointed out, “the safety data came out strikingly good. The overall dropout rate in the study for active TMS patients was 7.8%; for the sham patients it was 8.2%. The dropout rate because of side effects from TMS was 4.5%; in the sham [group] it was 3.5%. The only common side effects were headache or scalp discomfort. We had no seizures, no systemic side effects. In this population, adherence was really excellent—over 90%. We had no serious adverse events. TMS did not differ from the placebo in any of those things. There were no changes in cognition or auditory threshold, and we had a very high adherence rate.”
Despite the experience in the trial, however, TMS is not totally without risk. Lisanby, who was on the team that drafted a consensus statement for the International Society of Transcranial Stimulation, told Psychiatric Times: “At excessively high dosages, rTMS carries a risk of seizure. Patients need to be screened for seizure risk factors, and dosage needs to be set following safety guidelines. Dosage should be individualized for each patient using a thresholding procedure to reduce risk of seizure. When following the safety guidelines, and [with] proper medical screening, the risk of seizure with rTMS is low, but not zero.”
Elaborating on the consensus statement's call for a physician to be available during the TMS procedure, she said: “We wanted people to be clear on these points. The appropriate context is a medical context. There need to be safety measures in place in case of adverse events.”
poster:ttee
thread:727178
URL: http://www.dr-bob.org/babble/20070125/msgs/727178.html