Pam Harrison

April 07, 2016

PHILADELPHIA ― High-frequency deep transcranial magnetic stimulation (TMS) that targets signaling pathways involved in obsessive compulsive disorder (OCD) is showing promise as a novel approach for the treatment of this challenging disorder, new research shows.

"OCD unfortunately is a very disabling disorder for many of the people who have it, and about half of patients who have OCD are not able to recover adequately with currently approved treatments," Aron Tendler, MD, chief medical officer of Brainsway, told Medscape Medical News.

"In this feasibility study, we were trying to figure out which stimulation parameter would be most effective — low-stimulation frequency, at 1 pulse per second, or high-stimulation frequency, at 20 pulses per second," he added.

"We found a dramatic difference between the 20 pulses per second and the 1 pulse per second and between sham controls, so we now have an ongoing, multicenter study where we will be comparing the high-frequency 20-Hz stimulation to sham."

The research was presented here at the Anxiety and Depression Association of America (ADAA) Conference 2016.

Custom Coil

Researchers initially had to design a special coil capable of penetrating deep into the anterior cingulate cortex in order to provide electrical stimulation to the area. Conventional TMS coils used in the treatment of depression do not provide adequate stimulation to this particular area, said Dr Tendler.

A total of 40 patients with OCD that was unresponsive to medical therapy were involved in the study. Prior to receiving the electrical simulation, patients were provoked by whatever their compulsion was to ensure that circuits in the brain were activated when they were targeted for treatment.

Patients underwent five TMS treatments per week, each lasting about 18 minutes, for 5 weeks.

At the end of 5 weeks, patients treated with the 20-Hz stimulation protocol had a 27% decrease in scores on the Yale-Brown Obsessive Compulsive Scale (YBOCS) relative to baseline (P < .001) compared with only a 12% decrease among those who received the 1-Hz stimulation protocol.

Patients receiving sham treatment showed a 6% decrease in the YBOCS, the difference between the high-frequency stimulation protocol and sham control protocol being significant at P = .009.

Dr Tendler and colleagues also assessed patients before and after treatment using the Stroop test to see whether changes in scores on the YBOCS correlated with changes in electroencephalography (EEG) findings. As Dr. Tendler explained, patients with OCD show increased error-related negativity.

 

In the Stroop task, patients follow written instructions that show that a task is either congruent or incongruent. An incongruent task represents another type of provocation for OCD patients, he added.

"When looking at EEG activity over the anterior cingulate cortex, we saw that we had enhanced EEG activity in the high-frequency group, so TMS was making this area more active," Dr Tendler said.

"While this might be a stretch, we think we might be making patients more able to tolerate provocations through increased plasticity, which is always good."

Asked by Medscape Medical News to comment on what gave them the idea that electrical stimulation of the anterior cingulated cortex might relieve symptoms of OCD, Dr Tendler noted that in times gone by, physicians would perform an anterior cigulotomy as a way of treating severe OCD.

"Nowadays, we would do a functional cingulotomy using an electrode, but it's a much more invasive approach for what is a pretty common disorder," he said.

At least half of all patients with OCD do not respond well to medication. "All these patients can't go to surgery, so that's why we wanted to treat these patients with something that can be done in a doctor's office, which is TMS," Dr Tendler explained.

The new device designed specifically for OCD is currently available only for researchers who wish to use it in the setting of a clinical trial.

Unexpected Finding

Commenting on the findings for Medscape Medical News, Eric Hollander, MD, clinical professor of psychiatry and behavioral sciences, Albert Einstein College of Medicine, New York City, said that treatment-resistant OCD is a common and disabling disorder and that many patients fail to respond to first-line treatments.

"This study is of interest because it uses a new TMS coil [deep TMS] to target brain structures that are deeper in the brain (the anterior cingulate cortex) than current TMS targets," he said.

The anterior cingulate cortex is of interest, Dr Hollander added, because it is activated when patients get stuck in reacting to conflicting information — an action that may play an important role in OCD.

"It was unexpected that the higher-frequency stimulation would be more effective than the lower-frequency stimulation. But perhaps this works by allowing the frontal lobes to better regulate striatal hyperactivity that drives obsessive thoughts and compulsive behaviors," he said.

Dr Hollander also noted that the EEG findings from the study are "potentially important" because they could lead to the development of biomarkers that identify which patients are likely to improve with treatment and help track treatment response as well.

Dr Hollander has received a research grant from Brainsway. Dr Tendler is the chief medical officer of Brainsway Ltd, in Bala Cynwyd, Pennsylvania.

Anxiety and Depression Association of America (ADAA) Conference 2016: Abstract 122, presented April 1, 2016.

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