A Randomised, Double-Blind, Sham-Controlled Trial of Deep Brain Stimulation of the Bed Nucleus of the Stria Terminalis for Treatment-Resistant Obsessive-Compulsive Disorder

Abstract

Deep brain stimulation (DBS) is a promising treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, nine participants (four females, mean age 47.9 ±10.7 years) were implanted with DBS electrodes bilaterally in the bed nucleus of the stria terminalis (BNST). Following a one-month postoperative recovery phase, participants entered a three-month randomised, double-blind, sham-controlled phase before a twelve-month period of open-label stimulation incorporating a course of cognitive behavioural therapy (CBT). The primary outcome measure was OCD symptoms as rated with the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the blinded phase, there was a significant benefit of active stimulation over sham (p = 0.025, mean difference 4.9 points). After the open phase, the mean reduction in YBOCS was 16.6 ±1.9 points (χ2 (11) = 39.8, p = 3.8 x 10-5), with seven participants classified as responders. CBT resulted in an additive YBOCS reduction of 4.8 ±3.9 points (p = 0.011). There were two serious adverse events related to the DBS device, the most severe of which was an infection during the open phase necessitating device explantation. There were no psychiatric adverse events related to stimulation. An analysis of the structural connectivity of each participant's individualised stimulation field isolated right-hemispheric fibres associated with YBOCS reduction. These included subcortical tracts incorporating the amygdala, hippocampus and stria terminalis, in addition to cortical regions in the ventrolateral and ventromedial prefrontal cortex, parahippocampal, parietal and extrastriate visual cortex. In conclusion, this study provides further evidence supporting the efficacy and tolerability of DBS for individuals with otherwise treatment-refractory OCD and identifies a connectivity fingerprint associated with clinical benefit.

Distribution of electric field in patients with obsessive compulsive disorder treated with deep brain stimulation of the bed nucleus of stria terminalis

“…This centrally located nucleus has vast connections with many limbic-related networks, and dysfunction in these pathways is believed to have an important role in anxiety disorders, such as OCD [11,39]. A few clinical studies, including two randomized trials, have been published demonstrating an effect on obsessions, compulsions, and associated anxiety and depressive symptoms in this target [19,31,41,44,46,50].…”

Cortical-subcortical structural connections support transcranial magnetic stimulation engagement of the amygdala

“…Our findings underscore the relevance of examining downstream, subcortical effects of TMS, and the importance of mapping causal circuits underlying these effects. Circuit mapping approaches have been applied in DBS to increase the clinical efficacy of stimulation protocols [61][62][63][64][65] , and, as shown here, can be translated to TMS with the goal of informing treatment protocols. Ultimately, integrating insights derived from spTMS/fMRI brain-based readouts and diffusion-based connectivity into TMS protocols may help to increase the impact of TMS on both brain activity and behavior-thus enhancing the efficacy of therapeutic TMS for psychiatric conditions.…”

Commentary on the Continued Investigational Status of DBS for Psychiatric Indications

“…Recently reviewed OCD cases now amount to approximately 225 individuals in level 3 studies, or higher (as judged by the guidelines authors). In our estimation, and as discussed in more detail below, the features of predominantly non-US centers, varied DBS targets, and varied research protocols -regardless of data quality or efficacy results -still comprise an insufficiently uniform, controlled, or monitored dataset for a PMA application [35][36][37][38][39][40]. Sound medical research methods, accurately reported results, and sober analyses of efficacy and safety may support physician, patient, and medical society judgments about the value of DBS to treat OCD [41].…”