BOSTON — A novel stereotactic radiosurgery technique significantly reduces symptoms in patients with treatment-resistant major depressive disorder, according to a study presented at the American Society for Radiation Oncology (ASTRO) annual meeting.
Researchers led by Mohamed Khattab, MD, of the University of South Florida, performed the procedure – called stereotactic radiosurgical capsulotomy – in 20 patients, with results suggesting it could be life-saving.
“These were patients whose depression had not improved after several other treatments, and many were living with active thoughts of suicide,” Khattab said, in a September 29 news briefing.
Treatment-resistant major depressive disorder (trMDD) is defined as illness not improving after at least two antidepressant treatments and affects roughly three in 10 people with depression, the researchers explained. Most advanced treatment for trMDD are invasive and involve opening the skull, and are associated with potentially negative side effects, the group noted.
Conversely, stereotactic radiosurgical (SRS) capsulotomy uses highly focused radiation to create a tiny lesion in a brain pathway involved in mood and obsessive-compulsive symptoms and requires no incision. In 2022, Khattab’s group was the first in the world to report on SRS capsulotomy in a pilot study of three patients with trMDD, with promising results.
For this study, the researchers expanded the cohort to 20 patients who had previously failed cognitive therapy and multiple medications. All had been diagnosed with trMDD on average for more than 30 years, with many having multiple suicide attempts. Participants underwent SRS capsulotomy between 2020 and 2025 and were evaluated every three months, with a median follow-up of 38.6 months.
According to the results, depression scores improved significantly after treatment. Among 18 patients evaluated for depression symptoms, the average Beck’s Depression Inventory (BDI) score declined by 53% from before radiosurgery. Eleven patients (61%) had their BDI scores fall by at least half, while 16 (89%) experienced any numerical improvement.
The improvements were largely sustained, the researchers reported. 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.
Lastly, suicidal ideation also declined sharply. Before treatment, 14 of the 20 patients (70%) reported suicidal thoughts, while after treatment, one patient (5%) did.
“Is this a life-saving procedure, potentially?” Khattab said.
Ultimately, for people who have lived for years with severe depression despite trying nearly every available treatment, the possibility of another option is meaningful, Khattab said. The results warrant further studies to understand who may benefit most from SRS capsulotomy and how to deliver it as safely as possible, the group concluded.
Check out AuntMinnie’s full coverage of ASTRO 2026 on our ShowCast.