ASTRO 2026 | Stereotactic Radiosurgery Demonstrates Potential in Treating Severe Depression
Recent findings presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting highlight the promising role of incisionless radiosurgery as a treatment for patients suffering from severe, treatment-resistant depression. This prospective observational study focused on 20 individuals who underwent stereotactic radiosurgical capsulotomy—a non-invasive procedure that significantly reduced depression symptoms and suicidal thoughts among participants.
The study targeted patients whose depression had not responded to multiple previous treatments, including antidepressants and therapies such as electroconvulsive therapy. Following the radiosurgical intervention, a noteworthy reduction in depressive symptoms and suicidal ideation was observed. Initially, 14 of the 20 patients reported suicidal thoughts, but this number decreased to just one post-treatment. Additionally, among the patients evaluated for depression, 89% exhibited improvements in their self-reported depression scores. Most of these improvements were maintained over a median follow-up period exceeding three years.
Dr. Mohamed Khattab, the lead author and a radiation oncologist at the University of South Florida and Tampa General Hospital, emphasized the significance of these findings. “These were patients whose depression had not improved after several other treatments, and many were living with active thoughts of suicide,” he noted. “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 affects approximately 30% of individuals with depression. Those experiencing persistent symptoms often explore various therapeutic options, which can include alternative medications and more invasive methods. However, each treatment carries its own risks and may necessitate repeated interventions. The technique of stereotactic radiosurgical capsulotomy, which precisely targets brain pathways relevant to mood and obsessive-compulsive symptoms, offers a less invasive alternative without requiring an incision or an implanted device. Historically, this procedure has been primarily used for cases of treatment-resistant obsessive-compulsive disorder rather than depression.
In this study, participants received mask-based stereotactic radiosurgery utilizing a linear accelerator at Vanderbilt University Medical Center. They underwent evaluations every three months, combined with follow-up MRI scans, over a median of 38.6 months. The results demonstrated a significant decline in Beck’s Depression Inventory (BDI) scores, with an average reduction of 53% from pre-treatment levels. More than half of the patients experienced a decrease in BDI scores by at least 50%, and 61% continued to meet the criteria for a treatment response at the last follow-up.
Furthermore, cognitive function was preserved, with no evidence of cognitive decline or neurologic deficits post-treatment. Average ratings on the Montreal Cognitive Assessment reflected stable or improved scores among patients.
While these findings suggest that stereotactic radiosurgery could be a viable option for those with severe depression, Dr. Khattab reminds the medical community of the necessary caution due to the absence of a comparative group in the study. Consequently, larger, controlled trials are essential to verify these outcomes and assess the long-term risks and benefits.
Markus Bredel, MD, PhD, co-chair of ASTRO’s Functional Radiation Medicine Task Force, stresses the importance of these initial results, stating that further studies are crucial before considering this procedure as a standardized treatment option. Dr. Khattab and his team are hopeful that continued research will illuminate the potential of stereotactic radiosurgery to provide relief to those who have exhausted other treatment avenues.