Gamma Knife Brain Surgery Promising for Severe OCD

Megan Brooks

August 07, 2014

Gamma ventral capsulotomy (GVC), a type of ablative brain surgery, shows promise in the treatment of intractable obsessive-compulsive disorder (OCD), new research shows.

Results from the first randomized, double-blind, sham-controlled trial of the neurosurgical ablative technique showed that 3 of 8 patients (37.5%) who received active GVC responded at 12 months compared with none of 8 who received sham GVC.

At 12 months, OCD symptom improvement, determined on the basis of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), was significantly greater in the active GVC group than in the sham group (P = .046; dimensional Y-BOCS, P = .01).

At 54 months, 2 additional patients in the active group had responded, and 2 of 4 sham GVC patients who later received active GVC had responded by 12 months after surgery.

The study was published online July 23 in JAMA Psychiatry.

No Placebo Effect

First author Antonio C. Lopes, MD, PhD, of the OCD Clinic University of São Paulo School of Medicine in Brazil, and colleagues note that the fact that patients who did not receive active GVC did not improve "strongly" suggests the absence of a placebo effect.

The researchers add that the surgery was generally well tolerated. Most of the side effects were self-limited; the most serious adverse event was a radiation-induced cyst in 1 patient that was accompanied by delirium, confabulation, and visual hallucinations that responded to corticosteroids within a few days. However, memory deficits and executive function impairment persisted for 5 months and then subsided.

Commenting on the findings for Medscape Medical News, Sameer Sheth, MD, PhD, assistant professor of neurosurgery, New York Presbyterian Hospital/Columbia University Medical Center in New York City, who was not involved in the study, said: "These results are very promising, keeping in mind that these are very sick patients who have failed everything."

How does GVC work? "What we think is going on is that we are lesioning or disrupting connections between areas in the prefrontal cortex, specifically, the orbital frontal cortex and other structures in the brain, including the basil ganglia and other circuits involved in decision-making and cognition," Dr. Sheth explained.

"We think that there is overactivity in some of these circuits and regions, and so that disconnection or partial disconnection restores some balance in these cognitive decision-making circuits," he added.

Although this technique has been around years, this is "notably the first randomized, blinded, sham-controlled study of its kind. They did a great job of performing a rigorous trial, and the results are very encouraging," Dr. Sheth said.

Moving Target

He noted that only a small number centers do this procedure because it takes a "dedicated, committed, and experienced team of psychiatrists, neurosurgeons, neuropsychologists. We do it here at Columbia, and it's a very rigorous process in ensuring that the patients are appropriate, since these are irreversible lesions," Dr. Sheth said.

The "moving target" is picking the right patient, he noted, adding, "A big area of research is to figure out better who is going to respond."

Christian Rück, MD, PhD, of the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, has also researched capsulotomy for OCD but was not involved in the current study.

He told Medscape Medical News that this is "an important study that has been able to randomize subjects, something that is near impossible to do in invasive surgery, and the conclusions are that the surgery led to symptom reduction."

"To me, more studies on the efficacy and the long-term safety are needed if this procedure should be implemented on a larger scale. Studies that myself and others have done indicated quite large side effects," Dr. Ruck cautioned.

Dr. Lopes and colleagues would like to see an international registry be established to collect systematic data on patient characteristics, procedures, and outcomes related to the use of GVC for treatment of OCD.

The study was funded by the Foundation for Research Support of the State of São Paulo and the National Council for Scientific and Technological Development of Brazil. The authors have disclosed no relevant financial relationships.

JAMA Psychiatry. Published online July 23, 2014. Abstract

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