Conference Coverage

Deep transcranial magnetic stimulation alleviates OCD symptoms



– High-frequency deep transcranial magnetic stimulation (dTMS) directed at the anterior cingulate cortex and medial prefrontal cortex proved to be a safe and effective nonpharmacologic treatment for symptoms of obsessive-compulsive disorder in an international, randomized, sham-controlled, double-blind clinical trial that earned the device clearance for that indication from the Food and Drug Administration.

Lior Cormi, PhD, of Chaim Sheba Medical Center in Ramat Gan, Israel Bruce Jancin/MDedge News

Dr. Lior Cormi

The operative word here is “deep,” lead investigator Lior Carmi, PhD, explained in presenting the pivotal trial results at the annual congress of the European College of Neuropsychopharmacology.

“Deep TMS is a relatively new form of TMS that allows direct stimulation of deeper neuronal pathways than standard TMS. It induces a direct effective field at a depth of 3-5 cm below the skull, compared to less than 1.5 cm for the standard TMS figure-eight coil,” said Dr. Carmi, of Chaim Sheba Medical Center in Ramat Gan, Israel.

The brain circuitry involved in obsessive-compulsive disorder (OCD) is very well known. Multiple potential targets for intervention are available. Dr. Carmi and coinvestigators focused on the anterior cingulate cortex and medial prefrontal cortex, because this is an area that’s very much involved in OCD – it’s the generator of increased error-related negativity on the Stroop task – and it can be stimulated by dTMS, whereas standard TMS can’t reach it.

This was not only the first major clinical trial to successfully target the anterior cingulate cortex and medial prefrontal cortex using any form of TMS, it also was the first study to employ individually tailored symptom provocation using photos or a written script immediately before each treatment session. At the first patient encounter, the investigators created a list of what distressed that particular individual – for example, touching a public bathroom door handle or experiencing doubt about whether the stove had been left on – and then prior to each treatment session they deliberately provoked each study participant using representations of those triggers. The treatment, real or sham, didn’t begin until a patient’s distress level measured 4-7 on a visual analog scale.

“The idea is to deliver the treatment when the brain circuitry is aroused and not while the patient is thinking about the shopping he needs to get done after the session is over,” Dr. Carmi explained.

He was first author of the recently published pivotal study (Am J Psychiatry. 2019 May 21. doi: 10.1176/appi.ajp.2019.18101180) in which 99 adults aged up to age 65 years with OCD refractory to at least one selective serotonin reuptake inhibitor underwent real or sham dTMS every weekday for 5 consecutive weeks, plus four sessions during week 6. That’s a total of 29 sessions, featuring 2,000 magnetic stimulations per session. The study was conducted at 11 centers in the United States, Canada, and Israel. Participants had to remain on an approved drug therapy for OCD or engaged in psychotherapy throughout the study.

The primary efficacy outcome was the change in scores on the Yale-Brown Obsessive Compulsive Scale (YBOCS) from baseline to 6 weeks. Patients who received dTMS averaged a 6.0-point reduction, significantly better than the 3.3-point reduction in the sham-treatment group. The treatment response rate, as defined by at least a 30% reduction from baseline in YBOCS score, was 38% with dTMS, compared with 11% in controls. One month after the final treatment session, the response rate was 45% in the active-treatment arm, compared with less than 18% in the sham-treatment group.

In addition, 55% of patients in the active-treatment group achieved a partial response of more than a 20% reduction in YBOCS score, a rate slightly more than twice that in the sham group.

To put those findings in perspective, Dr. Carmi highlighted treatment effect–size results from OCD drug trials involving fluoxetine, fluvoxamine, sertraline, and paroxetine, all FDA-approved for treatment of OCD. The placebo-subtracted mean change in YBOCS scores in the pharmacotherapy trials were similar to the sham treatment–subtracted result in the dTMS study, with one important distinction: “In terms of change in YBOCS, it took 10-12 weeks to get those results in the drug trials, while we have shown this in a 6-week period of time,” he noted.

The only adverse effect associated with dTMS was headaches. They occurred in about one-third of the dTMS group and in a similar proportion of controls early on in the study, but they became a nonissue later.

“I have to say, we recruited 99 patients for the multicenter study, but only 2 of them dropped out because of side effects,” Dr. Carmi noted.

He reported having no financial conflicts of interest regarding the study, sponsored by Brainsway, which markets the dTMS device for the FDA-cleared indications of treatment-resistant depression and OCD.

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