BOSTON, September 28, 2026 — A highly focused, incisionless form of radiation therapy significantly reduced symptoms of major depression and thoughts of suicide among patients with severe, treatment-resistant psychiatric illness in a prospective observational study. Results will be presented today at the American Society for Radiation Oncology (ASTRO) Annual Meeting .
The study followed 20 patients with treatment-resistant depression who underwent stereotactic radiosurgical capsulotomy. Before treatment, 14 patients reported suicidal thoughts; afterward, just one did. Among patients evaluated for depression symptoms, 89% had some improvement in self-reported depression scores. Benefits were largely sustained over a median follow-up of more than three years.
“These were patients whose depression had not improved after several other treatments, and many were living with active thoughts of suicide,” said Mohamed Khattab, MD, lead study author and a radiation oncologist at the University of South Florida and Tampa General Hospital. “After treatment, 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.”
Treatment-resistant depression is generally defined as depression that does not improve adequately after at least two antidepressant treatments and is estimated to affect roughly three in 10 people with depression. For people with persistent symptoms, treatment options may include additional medications, ketamine-based therapies, electroconvulsive therapy or more invasive approaches such as radiofrequency ablation, but these treatments each carry risks of side effects and may require repeated treatments or surgery.
Stereotactic radiosurgical capsulotomy uses highly focused radiation to create a tiny lesion in a brain pathway involved in mood and obsessive-compulsive symptoms. Unlike conventional brain surgery, it requires no incision or implanted device. Capsulotomy has been used for decades to treat severe psychiatric illness using surgical and other ablative techniques. The radiosurgical approach, however, has been studied primarily for severe, treatment-resistant obsessive-compulsive disorder (OCD), rather than depression.
“This approach allows us to reach a very small target deep in the brain without opening the skull or placing electrodes,” Dr. Khattab said. “The goal is to interrupt a circuit that is contributing to severe, persistent symptoms while limiting effects on surrounding brain tissue.”
The current study builds on the team’s 2022 three-patient pilot of frameless stereotactic radiosurgical capsulotomy for refractory depression. In that initial report, all three patients experienced reductions or resolution of suicidal thoughts, with no observed cognitive decline or neurologic side effects.
For the new study, 20 patients with treatment-resistant depression, 10 of whom also had comorbid OCD, were treated at Vanderbilt University Medical Center for medical necessity after review by a multidisciplinary team that included psychiatry, neurosurgery and radiation oncology. Patients in the study had especially difficult-to-treat illness; all had previously received cognitive therapy and multiple medications, and many had not improved with ketamine, transcranial magnetic stimulation and/or electroconvulsive therapy.
Capsulotomy was delivered using mask-based stereotactic radiosurgery on a linear accelerator. Patients were separately offered enrollment in a prospective observational study from 2020 to 2025. Patients were evaluated every three months and underwent follow-up MRI scans. Median follow-up was 38.6 months.
Depression scores improved significantly after treatment. Among the 18 patients evaluated for depression symptoms, the average Beck’s Depression Inventory (BDI) score declined by 53% from before radiosurgery to the point of greatest improvement. Eleven patients (61%) had their BDI scores fall by at least half, while 16 (89%) experienced any numerical improvement.
The improvements were largely sustained. At last follow-up, the average depression score remained 47% below the pretreatment average. Nine of the 18 patients (50%) continued to meet the threshold for a treatment response, and 89% remained improved from baseline.
Suicidal ideation also declined sharply. Before treatment, 14 of the 20 patients (70%) reported suicidal thoughts. After treatment, one patient (5%) did.
Researchers found no overall evidence of cognitive decline after treatment. Average scores on the Montreal Cognitive Assessment (MoCA) were stable or numerically higher after radiosurgery, with all 20 patients showing stable or improved scores at the point of greatest improvement and 19 doing so at last follow-up.
“The preservation of cognitive function was one of the most important findings,” Dr. 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.”
Researchers also observed no neurologic deficits, apathy or personality changes. Three patients experienced moderate treatment-related side effects involving headache or dizziness; two also had larger-than-intended tissue changes visible on imaging. All recovered with steroid treatment.
The findings should be interpreted in context, Dr. Khattab said. The study was small and did not include a comparison group, so it cannot establish that radiosurgery itself caused the improvements. Larger, controlled studies will be needed to confirm the results and better understand which patients may benefit and what risks may emerge over time.
He said that caution is especially important given the history of ablative procedures for psychiatric illness. Modern stereotactic techniques are far more precise than historical psychosurgery, but radiosurgical capsulotomy still requires careful patient selection, informed consent and specialized multidisciplinary expertise. Although the radiation therapy technology used to deliver the treatment is widely available, Dr. Khattab emphasized that the procedure itself should remain limited to experienced teams.
“For people who have lived for years with severe depression despite trying nearly every available treatment, the possibility of another option is meaningful,” Dr. Khattab said. “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.”
ASTRO Expert Perspective
“For people with the most severe forms of depression, current treatments do not always bring enough relief. 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. The reduction in suicidal ideation is striking, but the findings should be viewed as early evidence from a specialized, multidisciplinary program. Larger studies will be needed before this approach can be understood as part of routine care,” said Markus Bredel, MD, PhD, co-chair of ASTRO’s Functional Radiation Medicine Task Force and the chair and Sylvester Professor of radiation oncology at the University of Miami Sylvester Comprehensive Cancer Center.
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This release contains updated study data provided by the authors. Where figures differ from the abstract, please use those reported in this release.
Study & Presentation Details
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