Brain Stimulation Techniques Promising for Resistant OCD

Pauline Anderson

May 22, 2015

TORONTO – Brain stimulation techniques ― either deep brain stimulation (DBS) or deep transcranial magnetic stimulation (dTMS) ― are increasingly in the spotlight as potential treatments for psychiatric disorders, and one of the main areas of interest is in obsessive-compulsive disorder (OCD).

New research on both interventions for OCD was released here at the American Psychiatric Association (APA) 2015 Annual Meeting.

One recent meta-analysis showed that DBS has a moderate effect in patients with OCD.

"The data are encouraging," said Steve Kisely, MD, PhD, professor of psychiatry and epidemiology, University of Queensland, Australia.

"It's a reversible surgical procedure that might be considered in nonresponsive cases, with the appropriate consideration of ethics and legal contraindications," he added.

History of Brain Manipulation

Dr Kisely noted that invasive brain manipulation in psychiatric patients dates back to 1891. In early prefrontal lobotomy programs, doctors performed the proceduring using an icepick under the eyelid through the roof of the orbit.

Between 1945 and 1955, 50,000 psychosurgeries were performed in the United States alone, and the discovery of the therapeutic value of prefrontal leucotomies won the Nobel Prize in medicine in 1949.

But by the 1970s, the intervention had fallen out of favor, partly because of concerns about cognitive side effects and increased mortality risk.

Now, though, there appears to be increasing interest in using the treatment in a number of psychiatric illnesses, including depression, Tourette's syndrome, and anorexia nervosa, as well as OCD. The resurgence, said Dr Kisely, can be attributed in part to better imaging techniques and tools.

"This is certainly a frontier being revisited."

The meta-analysis carried out by Dr Kinsely included five studies, all on OCD. He found no randomized, controlled studies of the use of DBS for depression. The studies were carried out between 2003 and 2010 and were of short duration.

"Ethically, you can't randomize people for months and months and months" and not provide a treatment, said Dr Kinsely.

The studies were small and included four to 16 patients; there was a total of 44 patients in the analysis.

The studies involved stimulation of the anterior limb of the internal capsule, the nucleus accumbens, or the subthalamic nucleus. They all compared active treatment against sham treatment.

Reduction in Symptom Severity

The analysis showed a mean reduction in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), a kind of gold standard for measurement for OCD symptom severity and type, of -8.93 (95% confidence interval, -12.21 to -5.65) for patients receiving active treatment as opposed to sham treatment.

"That's not remission; that is a moderate response," said Dr Kinsely. "It's not a cure by any stretch of the imagination."

A total Y-BOCS score of 8 to 15 is considered mild; 16 to 23, moderate; 24 to 31, severe; and 32 to 40, extreme.

Some studies showed a mild response in comorbid depression, as seen on the HAM-D scale. Only two studies looked at anxiety; the response was not significant.

A third of the patients in these studies experienced some postoperative problem. Although many adverse events were transient and generally mild, a small number of patients had severe side effects, such as an infections or hemorrhage.

"It's important to emphasize that this is not a treatment without risks," said Dr Kisely.

He also warned against the media "hype" surrounding DBS. "It's important that patients actually have a full and frank discussion and provide informed consent."

Dr Kisely noted that Australian guidelines recommend trying various treatments ― including exposure or ritual prevention therapy, two high-dose SSRIs, high-dose clomipramine (Anafranil, Covidien), and an MAO inhibitor ― before considering DBS.

OCD patients might want to consider less invasive transcranial magnetic stimulation before they opt for DBS.

A Less Invasive Technique

Elsewhere at the meeting, researchers from Israel revealed positive results using deep transcranial magnetic stimulation (dTMS) of the cortico-striato-thalamo-cortical (CSTC) circuit, an area known to be involved in OCD.

Compared with standard TMS, dTMS penetrates deeper into brain tissue ― 5 cm instead of 1 to 2 cm, according to Lior Carmi, PhD, a neuropsychologist in the Department of Psychology at the University of Tel Aviv, who presented the findings.

The pilot study included 40 OCD patients treated with dTMS at high frequency (20 Hz), low frequency (1 Hz), or no frequency (sham). The treatments lasted about 15 minutes and were administered daily for 5 weeks for a total of 25 treatments.

Prior to the treatment, the researchers succeeded in arousing symptoms of obsessiveness in the patients. For example, if a person's obsession had to do with making sure his doors were locked, Dr Carmi would press that patient about the possibility of having left the door open.

This, said Dr Carmi, is similar to the exposure/response prevention technique used in cognitive-behavioral therapy.

The high-frequency group had a 28% reduction in YBOC scores (from about 28 to 20). Scores in the low-frequency group were decreased by 12% (about 25 to 22), and those in the sham group had a 5% reduction in scores (about 26 to 25).

The improvement in the high-frequency group continued for 3 months.

Researchers took EEG measurements before and after the stimulation. They found that the error-related negativity (ERN) signal, which is aroused when any patient makes a mistake but even more so in OCD patients, was increased most in the high-frequency group.

The researchers had expected that a reduction in symptoms would correlate with a reduction in the ERN signal. "What happened was exactly the opposite," said Dr Carmi. "We changed the ERN, but we increased it, and this increase in ERN was correlated with reduction in symptom severity. It was an inverse correlation."

He thinks that the magnetic stimulation, in combination with the preceding provocation, might be increasing the plasticity or flexibility of the brain, allowing patients to be better able to change their behavior.

Dr Carmi believes that dTMS should be offered to OCD patients after treatment with medications fails but before trying DBS.

As with any treatment for OCD ― be it drugs, diet, DBS, or dTMS ― maintenance is "crucial," stressed Dr Carmi. "You have to keep the routine."

Dr Carmi and his team are now planning a study of the dTMS in 12 centers in the United States. They will compare the 20-Hz frequency coil with a sham to see whether results after 6 weeks of daily treatments are even better than results after 5 weeks.

Encouraging Results

Commenting on the dTMS study for Medscape Medical News, Daphne Voineskos, MD, a psychiatrist and clinical research fellow at the Center for Addiction and Mental Health (CAMH), in Toronto, said the results support previous research.

"We have seen some encouraging results, and this study is among them." She noted that this intervention has been used more for depression, but that researchers are now "starting to explore" it in OCD. CAMH investigators, too, are looking at transcranial magnetic stimulation in OCD patients, she said.

She noted that it makes sense that studies have shown that OCD patients who undergo dTMS have less depressive symptoms in addition to reduced obsessions and reduced symptoms of compulsive behaviors.

"One of the definitive parts of OCD is that your obsessions and compulsions are distressing to you, so if those are being decreased, your mood may get better."

In terms of areas of the brain involved in TMS, depression studies typically target parts of the dorsal lateral prefrontal cortex. In OCD, it is mostly the cingulate cortex, an area involved in the limbic system.

"This area integrates your thoughts and your emotions with your behaviors," said Dr Voineskos. "You can see on a theoretical level that it would be a pretty good target in that in the sort of pattern of OCD, these distressing behaviors are triggered by emotions and thoughts."

The dTMS study was funded by Brainsway. The authors report no relevant financial relationships.

American Psychiatric Association (APA) 2015 Annual Meeting. Presented May 16 and May 20, 2015.


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