183 - Radiosurgical Capsulotomy, a Novel Approach for Treatment-Resistant Major Depression: A Prospective Observational Study

10:45am - 10:55am ET

Room 160

Presenter(s)

Mohamed Khattab, MD - University of South Florida, Tampa, FL

M. H. Khattab¹, N. A. Al-Alusi², B. Chaballout³, A. D. Sherry⁴, G. Luo⁵, L. A. Cmelak⁶, J. E. Becker⁷, W. Petrie⁵, S. Bick⁵, and A. J. Cmelak⁵; ¹University of South Florida, Tampa General Hospital, Tampa, FL, ²University of California, San Francisco, San Francisco, CA, ³UCLA Radiation Oncology, Los Angeles, CA, ⁴Department of Radiation Oncology, Mayo Clinic, Rochester, MN, ⁵Vanderbilt University Medical Center, Nashville, TN, ⁶University of Tennessee Health Science Center, Memphis, TN, ⁷Vanderbilt University Medical Center, NASHVILLE, TN

Purpose/Objective(s): Bilateral anterior capsulotomy by invasive surgical methods such as radiofrequency ablation has been reported for treatment-resistant major depressive disorder (trMDD). While stereotactic radiosurgical (SRS) capsulotomy has been reported for intractable Obsessive Compulsive Disorder (OCD), SRS capsulotomy was never previously reported for trMDD. In 2022, our group was the first in the world to report on SRS capsulotomy in a pilot study of 3 patients with trMDD who were treated with promising results. The purpose of this study is to report the efficacy and safety among a larger cohort of 20 patients with MDD treated with SRS capsulotomy.

Materials/Methods: Patients with trMDD and/or intractable OCD with secondary MDD were treated for medical necessity after multidisciplinary review by psychiatry, neurosurgery and radiation oncology with consensus recommendation for SRS capsulotomy. All patients had failed cognitive behavioral therapy and numerous medical therapies. Additionally, 40% were refractory to ketamine for trMDD, 35% had failed prior transcranial magnetic stimulation, and 55% had failed electroconvulsive therapy. Patients were offered elective enrollment on a prospective observational study from 2020 to 2025. Capsulotomy was accomplished by mask-based linear accelerator SRS. Patients were followed every 3 months with examination and magnetic resonance imaging (MRI), including tractography. During visits, Beck’s Depression Inventory (BDI) measured efficacy in MDD response and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) measured efficacy in OCD response. Montreal Cognitive Assessment (MoCA) evaluated cognition. Suicidal ideation (SI) was monitored.

Results: Median follow-up was 1,073 days (35 months). 70% of patients endorsed active SI pre-SRS capsulotomy. At last follow-up post-SRS only 10% endorsed any degree of SI and notably with decreased intensity. The mean pre-SRS BDI measuring MDD was 32.4. There was significant improvement in MDD symptoms with a mean BDI score at time of maximal improvement of 15.9 (p<0.001) and at last follow-up of 17.7 (p<0.001). Among patients with OCD symptoms, the mean pre-SRS Y-BOCS was 30.0. There was significant improvement with a mean Y-BOCS score at time of maximal improvement of 17.2 (p<0.001) and at last follow-up of 19.9 (p=0.010). Among all patients, the mean pre-SRS MoCA was 26.3. There was a significant improvement with a mean MoCA score at time of maximal improvement of 28.9 (p=0.002) and at last follow-up of 28.6 (p=0.005). There were no neurological deficits, apathy or personality changes. Three patients had G2 toxicity with headache and dizziness and imaging with larger than intended necrosis; all improved with steroids.

Conclusion: We report the first-in-world experience of SRS capsulotomy in 20 patients with MDD (trMDD and/or intractable OCD with secondary MDD). Treatment resulted in a significant decrease in suicidal ideation and with durable improvements in depression and cognition. (NCT04688554)