Focused brain radiation could ease severe, tough-to-treat depression

30 Sep 2026, 13:40 · Medical Xpress

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Researchers say they've found an incision-free way to treat the brains of people stricken with severe, treatment-resistant depression, bringing what looks to be lasting relief. It's a small study—just 20 participants—so larger trials are needed. But there seems to be promise in the approach, which focuses radiation at a key spot in the brain.

Fourteen of the 20 participants had depression so bad it had led to suicidal thoughts. However, those thoughts receded for all but one after treatment, the researchers said.

Overall, 89% of participants saw an improvement in scores measuring depression.

These benefits appear to have been sustained for a median of three years after treatment, the study found. That means half of the participants maintained positive treatment effects for a longer time and half did not.

"For people who have lived for years with severe depression despite trying nearly every available treatment, the possibility of another option is meaningful," said lead author Dr. Mohamed Khattab, a radiation oncologist at the University of South Florida and Tampa General Hospital.

"These results give us a reason to study this approach more rigorously, so we can understand who may benefit and how to deliver it as safely as possible," he said.

Khattab's team presented its findings in Boston at the annual meeting of the American Society for Radiation Oncology (ASTRO). The study was also published in the International Journal of Radiation Oncology*Biology*Physics.

The study focused on people battling treatment-resistant depression, defined as depression that persists after at least two antidepressant treatments. About 30% of patients with depression end up being treatment-resistant, according to background information from an ASTRO news release.

The patients in the new study had tried other treatments, including cognitive therapy, multiple medications, ketamine, transcranial magnetic stimulation, electroconvulsive ("shock") therapy and invasive brain interventions such as ablation. These treatments can come with side effects, and some require surgery.

The new technique is called stereotactic radiosurgical capsulotomy. It involves the use of highly targeted radiation to form a tiny lesion in a brain circuit that's known to play a role in mood and obsessive-compulsive disorders.

The procedure requires no cutting or implanted device.

It's already been used to treat obsessive-compulsive disorder (OCD), but its use against tough-to-treat depression is new.

"This approach allows us to reach a very small target deep in the brain without opening the skull or placing electrodes," Khattab explained in the ASTRO news release. "The goal is to interrupt a circuit that is contributing to severe, persistent symptoms while limiting effects on surrounding brain tissue."

Khattab's team had tried the approach in 2022 in three patients with treatment-resistant depression, and it had seemed to safely help ease symptoms.

Ten of the 20 participants in the new study also had OCD alongside their depression.

Following stereotactic radiosurgical capsulotomy therapy, 18 of the participants were evaluated for depression symptoms and saw an average 53% decline in symptom scores, based on a standard test.

There was an especially big impact in lessening suicidal thoughts, the researchers noted.

"We saw meaningful reductions in depression symptoms and suicidal thoughts among a majority of patients, without the severe or permanent neurologic or cognitive side effects that people may fear when they hear about procedures involving the brain," Khattab said.

The participants showed no signs of neurologic deficits, apathy or personality changes following the procedure. Khattab's team also found no evidence of cognitive decline after treatment.

"The preservation of cognitive function was one of the most important findings," Khattab said. "People understandably worry about whether a procedure involving the brain could change how they think or function. In our study, cognition was not compromised as depression symptoms declined."

The only side effects noted were mild—three patients experienced headache or dizziness. Two others showed larger-than-expected brain tissue changes after their therapy, which the researchers said resolved after steroid treatment.

The Florida team noted that the study did not include a comparison group, so it cannot prove that the radiation treatment caused the decline in depression. Better, larger trials are warranted, Khattab said.

"This study is important because it evaluates a highly targeted, incisionless approach in patients who had already tried multiple therapies, while also tracking cognition and safety over time," Dr. Markus Bredel, co-chair of ASTRO's Functional Radiation Medicine Task Force, said in the ASTRO news release. He was not involved in the new research.

Bredel also stressed that "larger studies will be needed before this approach can be understood as part of routine care." He is also a professor of radiation oncology at the University of Miami Sylvester Comprehensive Cancer Center.

Because these findings were presented at a medical meeting, they should be considered preliminary until published in a peer-reviewed journal.

Publication details

M.H. Khattab et al, Radiosurgical Capsulotomy, a Novel Approach for Treatment-Resistant Major Depression: A Prospective Observational Study, International Journal of Radiation Oncology*Biology*Physics (2026). DOI: 10.1016/j.ijrobp.2026.06.096

Journal information: International Journal of Radiation Oncology*Biology*Physics

Key medical concepts

Suicidal ideationCognitive function

Clinical categories

PsychiatryPsychology & Mental health Who's behind this story?

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