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Noninvasive treatment for refractory OCD, major depression shows promise for lifelong benefits

Oct. 15, 2020, 9:21 AM

Mohamed Khattab, MD, left, and Anthony Cmelak, MD, are studying the use of a linear accelerator to target the areas in the brain’s limbic system that control the pathway for obsessive compulsive disorder. (photo taken prior to social distancing)
Mohamed Khattab, MD, left, and Anthony Cmelak, MD, are studying the use of a linear accelerator to target the areas in the brain’s limbic system that control the pathway for obsessive compulsive disorder. (photo taken prior to social distancing) photo by Susan Urmy

by Kelsey Herbers

Four months ago, a multidisciplinary care team at Vanderbilt University Medical Center treated a patient with lifelong major depressive disorder (MDD) and obsessive compulsive disorder (OCD) — conditions that left her debilitated with intrusive thoughts, constant fear, suicidal intent and anorexia.

Today, that patient is back to playing sports, socializing with friends and leaving her house, all thanks to a new noninvasive procedure that “rewires” the circuit in the brain responsible for OCD and MDD symptoms by destroying the tissue connecting pathways implicated in these diseases.

The procedure uses a linear accelerator — a machine commonly used to deliver radiation therapy for cancer patients — to target the areas in the brain’s limbic system that control the pathway for OCD and MDD.

While surgeons have long treated patients with neuropsychiatric diseases by interrupting this pathway, the only methods available required cutting into the skull and brain, which often led patients to decline the procedure even when all other treatments failed.

Other procedures such as deep brain stimulation are also sometimes refused by patients who do not want permanent implants in the brain, the risks of surgery or a subcutaneous battery pack (pulse generator), which requires lifelong maintenance.

Using a linear accelerator, a team of radiation oncologists, neurosurgeons, psychiatrists and physicists were able to disrupt this circuit using highly focused X-ray beams coming from multiple directions to each side of the patient’s head with sub-millimeter accuracy. The patient was immobilized using an aquaplast mask that allowed her to see and breathe during the procedure but kept her from moving her head.

The procedure required two hours of radiation over the course of two days. Because the procedure is noninvasive and the mask may be taken off and replaced if the patient desires, the care team was able to give the patient breaks throughout the procedure to let her rest and ensure she was comfortable at every step.

The patient noticed an improvement in her quality of life within four to six weeks and has since begun discontinuing many of her medications. She has not required any further electroconvulsive therapy (ECT), which she was receiving twice per week prior to the procedure, and her OCD symptoms have been reduced by more than 50%. Her depression symptoms have also decreased by 30%, all in four months’ time.

“What we’re doing is providing an incisionless treatment that can get patients off ECT and lifelong medications for OCD and get them back into society as a functioning person. With a one-to-two-day outpatient treatment, this is groundbreaking,” said Anthony Cmelak, MD, professor of Radiation Oncology at Vanderbilt-Ingram Cancer Center (VICC).

“This procedure involves no pins or invasive immobilization and no risk of pins puncturing a vessel or the skull, potentially causing a fracture. It additionally does not require anesthesia and does not have the risks associated with surgery, where intracranial hemorrhage or infection are possible,” added Mohamed Khattab, MD, chief resident in the Department of Radiation Oncology at VICC. “We’re trying to bring this frameless radiosurgery to the forefront because that’s what patients are demanding — the least invasive treatment for their functional disease.”

According to Khattab, OCD is extremely prevalent, affecting about 3% of the general population. The disease typically begins at a young age and worsens over time, often causing a lifetime of debilitating fear and intrusive thoughts that prevent the person from working, building social connections and functioning outside of the home.

At least 20% of patients with OCD don’t respond to any medications, and while ECT can provide some short-term relief in severe cases, it can lose its effectiveness when used chronically and can have negative effects on memory.

This lack of treatment options has contributed to patients with OCD having a 10-fold increased risk of dying by suicide than the general population, and many people with OCD also experience major depression.

The linear accelerator-based procedure performed at VUMC is meant to be a one-time treatment with lifelong results. Because linear accelerators are commonly available within most health systems, the VUMC team hopes this treatment can quickly become widespread and easily accessible to patients. The procedure is also cost-effective for both patients and insurers.

“When we look at the cost burden to society and to health care systems, the burden of neuropsychiatric disease is staggeringly more than heart disease and all cancer care. As radiation oncologists who most commonly treat cancer patients, we find ourselves compelled to use our advanced technologies when possible to address other health care challenges,” said Khattab.

“It excites us that we can provide an incisionless procedure that reduces costs for the patient and the payer and more importantly bring more people into the workforce and into society in the way they desire.”

Under the mentorship of Cmelak, Khattab has been awarded more than $430,000 in funding from Varian Medical Systems and Brainlab to treat patients using the procedure and to obtain advanced imaging to further examine how circuitry and functionality of the brain changes over time after the therapy.

The team will use functional imaging at baseline and at follow-up time intervals to see which pathways are altered to further advance understanding of neuropsychiatric disease and to refine the pertinent targets. The team has also received funding to see if the procedure can be used to treat other conditions.

“We have been performing linear accelerator radiosurgery at Vanderbilt for malignancies since 1990 and for non-neoplastic diseases such as arteriovenous malformations since 1994. Parkinson’s disease, essential tremor and trigeminal neuralgia have been treated since 2010. We are excited to expand the potential indications for radiosurgery not only for OCD, but for patients with refractory depression and even chronic pain,” said Cmelak.

In addition to Cmelak and Khattab, the VUMC multidisciplinary team also includes William Petrie, MD, professor of Clinical Psychiatry and Behavioral Sciences, Guozhen Luo, MS, medical physicist in the Department of Radiation Oncology, and Hamid Shah, MD, assistant professor of Neurosurgery, who were instrumental in coordinating care for this patient.

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