EXPERT ANALYSIS FROM THE ANXIETY AND DEPRESSION CONFERENCE 2017
SAN FRANCISCO (FRONTLINE MEDICAL NEWS) – Mounting evidence suggests that transcranial magnetic stimulation is an effective noninvasive therapy for obsessive-compulsive disorder refractory to first-line medications, Eric Hollander, MD, said at the annual conference of the Anxiety and Depression Association of America.
A novel treatment for obsessive-compulsive disorder (OCD) would be most welcome. This is a disorder that’s common – affecting 2%-3% of the population – debilitating, and notoriously tough to treat. Roughly half of patients with OCD don’t respond to first-line therapy, which is selective serotonin reuptake inhibitors, cognitive-behavioral therapy, or both, according to Dr. Hollander , director of the autism and obsessive-compulsive spectrum program as well as the anxiety and depression program at Albert Einstein College of Medicine in New York.
He has extensive experience with transcranial magnetic stimulation (TMS). Indeed, Dr. Hollander was a coinvestigator in the pivotal, double-blind, randomized, 212-patient multicenter clinical trial that earned deep TMS U.S. Food and Drug Administration approval for treatment of major depressive disorder.
Four companies now have FDA-cleared TMS devices indicated for treatment of major depression: Brainsway, which markets a dTMS device, and Neuronetics, MagVenture, and Magstim, which sell repetitive TMS (rTMS) devices that do not penetrate as deeply beneath the skull as dTMS and therefore target different brain structures.
TMS for OCD is, at present, off-label therapy. Yet, there is now sufficient experience derived from formal clinical trials and off-label use in clinical practice to be able to state that the standard target area for rTMS is the supplementary motor area (SMA), according to Dr. Hollander.
He was senior author of a randomized open-label pilot study involving 50 consecutive OCD patients refractory to SSRIs. Half were assigned to a popular second-line strategy: augmentation with antipsychotic agents. The other half received five 20-minute-long rTMS sessions per week for 3 weeks using low-frequency 1 Hz bilateral stimulation of the SMA.
At 3 weeks, the treatment response rate as defined by at least a 25% reduction from baseline on the Yale-Brown Obsessive-Compulsive Scale ( YBOCS ) was 68% in the rTMS group, compared with 24% in the control arm. Thus, rTMS was better than treatment as usual ( J Psychopharmacol. 2016 Jun;30:568-78 ).
“That’s considerable improvement after only 3 weeks of stimulation, which is a very short time, compared to other OCD treatments,” the psychiatrist noted.
In another study, Dr. Hollander and his coinvestigators used the same rTMS regimen targeting the SMA in 22 SSRI-refractory OCD patients. After 3 weeks of rTMS, 12 of the 22 were treatment responders and 3 patients were in remission.
Moreover, these effects were long-lasting. At 6 months, 13 patients were responders and 4 were in remission, and, at 12 months – nearly a year after their relatively brief course of rTMS – there were 12 responders and 3 remitters.
Participants also showed significant reductions on both the Hamilton Depression Rating Scale ( HAM-D ) and the Hamilton Anxiety Rating Scale ( HAM-A ), effects that were sustained during follow-up, although the improvement in OCD symptoms was more impressive, he said.
Other investigators also have reported positive results using rTMS for OCD, with the first publication coming from Italian investigators more than a decade ago ( Int J Neuropsychopharmacol. 2006 Feb;9:95-100 ).
Studies of dTMS for OCD are a more recent development. In 2016, investigators reported on 40 OCD patients treated double-blind with either high-stimulation dTMS at 20 Hz, low-stimulation at 1 Hz, or a sham magnetic coil daily for 5 weeks. The target areas were the medial prefrontal and anterior cingulate cortices, areas too deep to be reached using rTMS. At the 5-week mark, the patients who received high-stimulation dTMS showed a mean 26% improvement in YBOCS scores, compared with a 6% reduction in the low-stimulation and sham-treatment arms.
In this study, electroencephalogram evoked potential responses over the anterior cingulate cortex correlated with clinical response, thus providing a welcome biomarker of treatment efficacy.
How TMS works in OCD
TMS involves placing a coil on the scalp to create a magnetic pulse that passes through the skull and achieves predictable changes in neuronal activity in brain tissue, either exciting or deactivating target regions depending upon whether high- or low-frequency TMS is applied.
Brain imaging studies show that OCD is characterized by hyperactivation of the medial frontal cortex and the SMA. The dysfunctional circuitry of OCD has been worked out. It’s striatally based, involving frontal-striatal-thalamic circuits. The SMA sits right above the anterior cingulate cortex and provides access to these key pathways. Basically, increased neuronal activity in the frontal lobes of OCD patients results in miscommunication with the striatal and thalamic regions, with resultant thalamic hyperactivity. This failure of cortical inhibition leads to persistent intrusive thoughts and behaviors, Dr. Hollander explained.
The neural circuitry of OCD is distinct from that of other anxiety disorders, and it appears that TMS is not as effective in those disorders as in OCD, he added.
The anterior cingulate is one step closer than the SMA to the frontal-striatal-thalamic circuits, which are of particular therapeutic interest in OCD, and it’s accessible by dTMS. Anterior cingulate activity is decreased in OCD. When high-frequency dTMS revs up that activity, the result is symptomatic improvement. Of note, the anterior cingulate also is the target for cingulotomy , an established surgical treatment for OCD.
Dr. Hollander reported receiving research funding from the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke. He serves as a consultant to a number of pharmaceutical companies.