Objective To address the limitations of current trial-and-error programming strategies in deep brain stimulation (DBS) for refractory obsessive-compulsive disorder (OCD), we implanted patients with sensing-capable DBS devices to identify neural biomarkers that could provide objective feedback to the clinician about therapeutic efficacy.

Methods We conducted an early feasibility study in 10 patients with severe, treatment-resistant OCD. All subjects received bilateral DBS leads targeting the ventral internal capsule (VC) and the second half of the cohort also received strip electrodes over the bilateral orbitofrontal cortex for recording only. All leads were connected to investigational, bidirectional DBS devices. After implantation, participants returned for scheduled programming visits to determine optimal stimulation parameters (Phase 1). In Phase 2, patients completed a course of exposure and response prevention (ERP) psychotherapy, and in Phase 3, patients underwent a double-blind discontinuation of DBS to test true vs. sham response. Phase 4 was an open-label follow-up. We administered standardized symptom scales throughout the study and used non-parametric repeated-measures analyses to analyze neuropsychological data.

Results All patients elected to resume stimulation after a discontinuation phase. At the end of the study, the mean reduction in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was 22 points or 60% across all patients with 8 patients demonstrating full response (>35% decrease in Y-BOCS). All participants also experienced reduced depression severity.

Conclusions In patients with refractory OCD, we demonstrate excellent clinical response to VC DBS. We show feasibility of recording neural data both at home and in the clinic on board bidirectional DBS devices.

W.K.G. receives research support from Abbott Laboratories and royalties from Nview, LLC and OCDscales, LLC. S.A.S. is a consultant for Boston Scientific, Abbott, Neuropace, Koh Young, and Zimmer Biomet, and co-founder of Motif Neurotech. E.A.S. receives direct funding from the International OCD Foundation as well as MHNTI for providing trainings on treating obsessive-compulsive disorder with psychotherapy. He was a consultant for Brainsway and Biohaven Pharmaceuticals in the past 36 months. He owns stock options less than $5000 in NView (for distribution of the Y-BOCS and CY-BOCS) and receives royalties from OCD Scales LLC (for distribution of the Y-BOCS and CY-BOCS). He receives book royalties from Elsevier, Wiley, Oxford, American Psychological Association, Guildford, Springer, Routledge, and Jessica Kingsley.

NCT04281134

The research was supported by the National Institutes of Health NINDS BRAIN Initiative via contracts UH3NS100549, by the McNair Foundation, and by the Gordon and Mary Cain Pediatric Neurology Research Foundation. Medtronic donated the DBS devices and related hardware.

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The institutional review board of Baylor College of Medicine gave ethical approval for this work.

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