Dramatic Improvement in Suicidal Ideation After Brain Radiosurgery Capsulotomy

Patients with treatment-resistant depression and suicidal ideation had significant symptomatic improvement after radiosurgical treatment of a brain pathway involved in mood and obsessive-compulsive behavior, a small clinical trial showed.

Suicidal ideation resolved in 13 of 14 patients, and depression symptom scores decreased by more than half on average across 18 evaluable patients treated with radiosurgical capsulotomy. Eleven patients had 50% or more decrease in their individual Beck Depression Inventory (BDI) score. All but two of 20 patients enrolled in the study had some degree of improvement from baseline. The treatment effect proved durable in most patients followed for a year or longer.

No patient exhibited neurologic deficits, cognitive decline, personality changes, or signs of hemorrhage or infection after treatment, reported Mohamed Khattab, MD, of the University of South Florida in Tampa, at the American Society for Radiation Oncology meeting in Boston.

“Thirteen of 14 patients with suicidal ideation at presentation — 93% of the patients — had resolution of their suicidal ideation at last follow-up,” said Khattab. “So, is this a life-saving treatment? Potentially. Among all patients, improvement in depression was seen as early as 3 months, and this improvement was sustained at least follow-up. … These results are particularly impressive considering the severity of disease of our patients and that they were refractory to other interventions.”

“The study was limited by having a small sample size treated at a single institution and no sham control,” he added. “In the future we would like to conduct a sham-controlled, randomized study, also incorporating functional imaging. We are also having active discussions with our colleagues in psychiatry about how to best incorporate these treatments to optimize the sequence of treatments.”

The results are impressive but have to be viewed within the context of a small, single-center trial, according to ASTRO expert Markus Bredel, MD, PhD, of the University of Miami Sylvester Comprehensive Cancer Center.

“For people with the most severe forms of depression, current treatments do not always bring enough relief,” said Bredel. “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.”

Capsulotomy is not new. Variations of the procedure, primarily surgery and ablative techniques, have been used for decades to treat severe psychiatric illness, Khattab noted. Stereotactic radiosurgical (SRS) capsulotomy has been studied primarily in the setting of severe, treatment-resistant obsessive-compulsive disorder (OCD).

SRS “allows us to reach a very small target deep in the brain without opening the skull or placing electrodes,” he said. “The goal is to interrupt a circuit that is contributing to severe, persistent symptoms while limiting effects on surrounding brain tissue.”

A prior proof-of-principle study involving three patients with treatment-refractory depression showed significant reduction in or resolution of suicidal thoughts and no evidence of cognitive decline or neurologic side effects. The results provided the basis for the current study, involving 20 patients with longstanding treatment-resistant depression, half of whom had comorbid OCD.

The patients had a median age of 60 and an average symptom duration of 33 years. Seven patients had proven refractory to transcranial magnetic stimulation, 12 refractory to electroconvulsive therapy, and eight refractory to ketamine.

The 18 evaluable patients had a mean baseline BDI score of 32.4 on the scale (0-63 points possible), which improved to 15.5 among the 13 patients followed for more than a year after SRS capsulotomy. The effect on depressive symptoms occurred quickly, as the mean BDI had declined to 18.2 after 3 months. In the 10 patients without OCD, the mean BDI decreased from 34.6 at baseline to 15.8 at last follow-up. The mean BDI for all 20 patients was 17.3 at last follow-up (maximum of 35 months).

Among the 10 patients with comorbid OCD, the mean score on the Yale-Brown Obsessive Compulsive Scale (range 0-40, lower scores are better) decreased from 30.0 before treatment to 17.7 at 3 months. Two patients followed for 12 months had these scores drop to 8 and 16, respectively; scores remained at an average 18.8 among the seven with follow-up more than 12 months.

Investigators assessed cognitive function in the 20 patients by means of the Montreal Cognitive Assessment (MoCA). The 20 patients had a mean MoCA score of 26.3 at baseline and a range from 27 to 29 at follow-up assessments at 12 months and beyond.

Khattab acknowledged that the study was conducted entirely at Vanderbilt University Medical Center in Nashville, Tennessee, while he was employed there.