Long-Term Safety and Efficacy of Focused Ultrasound Capsulotomy for Obsessive-Compulsive Disorder and Major Depressive Disorder

Clement Hamani; Benjamin Davidson; Jennifer S Rabin; Maged Goubran; Lyndon Boone; Kullervo Hynynen; Emmanuel De Schlichting; Ying Meng; Yuexi Huang; Ryan M Jones; Anusha Baskaran; Tulip Marawi; Margaret Anne Richter; Anthony Levitt; Sean M Nestor; Peter Giacobbe; Nir Lipsman

doi:10.1016/j.biopsych.2024.08.015

Long-Term Safety and Efficacy of Focused Ultrasound Capsulotomy for Obsessive-Compulsive Disorder and Major Depressive Disorder

Biol Psychiatry. 2024 Aug 24:S0006-3223(24)01548-8. doi: 10.1016/j.biopsych.2024.08.015. Online ahead of print.

Authors

Clement Hamani¹, Benjamin Davidson², Jennifer S Rabin³, Maged Goubran⁴, Lyndon Boone⁵, Kullervo Hynynen⁴, Emmanuel De Schlichting⁶, Ying Meng², Yuexi Huang⁷, Ryan M Jones⁷, Anusha Baskaran⁸, Tulip Marawi⁷, Margaret Anne Richter⁹, Anthony Levitt¹⁰, Sean M Nestor¹¹, Peter Giacobbe¹², Nir Lipsman¹³

Affiliations

¹ Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Sunnybrook Research Institute, Toronto, Ontario, Canada. Electronic address: clement.hamani@sunnybrook.ca.
² Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Sunnybrook Research Institute, Toronto, Ontario, Canada.
³ Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Sunnybrook Research Institute, Toronto, Ontario, Canada; Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
⁴ Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Sunnybrook Research Institute, Toronto, Ontario, Canada; Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
⁵ Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
⁶ Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
⁷ Sunnybrook Research Institute, Toronto, Ontario, Canada.
⁸ Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Sunnybrook Research Institute, Toronto, Ontario, Canada.
⁹ Sunnybrook Research Institute, Toronto, Ontario, Canada; Frederick W. Thompson Anxiety Disorders Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
¹⁰ Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
¹¹ Sunnybrook Research Institute, Toronto, Ontario, Canada; Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
¹² Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
¹³ Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Sunnybrook Research Institute, Toronto, Ontario, Canada. Electronic address: nir.lipsman@sunnybrook.ca.

PMID: 39187171
DOI: 10.1016/j.biopsych.2024.08.015

Abstract

Background: Magnetic resonance-guided focused ultrasound (MRgFUS) trials targeting the anterior limb of the internal capsule have shown promising results. We evaluated the long-term safety and efficacy of MRgFUS capsulotomy in patients with obsessive-compulsive disorder (OCD) and major depressive disorder (MDD).

Methods: This phase 1, single-center, open-label study recruited patients with treatment-resistant OCD and MDD. Outcomes were measured 6 months, 12 months, and 18 to 24 months (long term) after MRgFUS capsulotomy. Neuropsychological testing and neuroimaging were conducted at baseline and 12 months postoperatively. The primary outcome was safety. The secondary outcome was clinical response, defined for OCD as a ≥35% improvement in Yale-Brown Obsessive Compulsive Scale scores and for MDD as a ≥50% reduction in Hamilton Depression Rating Scale scores compared with baseline.

Results: No serious adverse effects were registered. In patients with OCD (n= 15), baseline Yale-Brown Obsessive Compulsive Scale scores (31.9 ± 1.2) were significantly reduced by 23% (p = .01) at 6 months and 35% (p < .0001) at 12 months. In patients with MDD (n = 12), a 26% and 25% nonsignificant reduction in Hamilton Depression Rating Scale scores (baseline 24.3 ± 1.2) was observed at 6 months and 12 months, respectively. Neuropsychological testing revealed no negative effects of capsulotomy. In the OCD and MDD cohorts, we found a correlation between clinical outcome and lesion laterality, with more medial left-placed lesions (OCD, p = .08) and more lateral right-placed lesions (MDD, p < .05) being respectively associated with a stronger response. In the MDD cohort, more ventral tracts appeared to be associated with a poorer response.

Conclusions: MRgFUS capsulotomy is safe in patients with OCD and MDD and particularly effective in the former population.

Keywords: Capsulotomy; Depression; Focused ultrasound; Long term; Obsessive-compulsive disorder.