Multimodal characterization of deep brain stimulation for obsessive-compulsive disorder

Background: Obsessive-compulsive disorder (OCD) is a chronic and disabling condition, with up to 40-60% of patients failing to achieve adequate response to first-line treatments. This unmet clinical need has driven the development of circuit-based interventions targeting fronto-striatal dysfunction. Deep brain stimulation (DBS) is an invasive neurostimulation therapy that is able to direct modulate impaired circuitry underlying cognitive-affective rigidity. DBS represents a promising, yet underutilised, therapeutic approach for treatment-resistant OCD (TR-OCD). However, critical gaps remain in identifying predictors of response, optimising targeting strategies, and understanding the broader psychosocial and phenomenological effects of treatment. This study integrates multi-modal evidence across a series of investigations to advance a more precise, patient-centred framework for DBS in OCD.

Methods: A comprehensive, multi-method approach was employed. First, a systematic review of all published investigations synthesised the current evidence base for DBS in OCD. Second, a phase II open-label longitudinal trial was conducted in eight individuals with TR-OCD receiving DBS targeting the nucleus accumbens (NAc). Clinical outcomes included OCD symptom severity as well as depression, anxiety, and insight, analysed using mixed linear modelling across nine months. Neuroimaging data were processed using Lead-DBS to map electrode localisation within a standardised connectomic framework. Third, responders participated in in-depth qualitative interviews, analysed using interpretative phenomenological analysis (IPA). Finally, findings were integrated with clinical expertise, patient and caregiver perspectives, and existing literature to generate translational clinical recommendations.

Results: Across 7 randomised controlled trials and 17 open-label studies, DBS demonstrates consistent efficacy in TR-OCD, with response rates ≥60% [1]. In our cohort, 75% (6/8) achieved clinically significant response, patients experienced an average improvement of 45% in obsessions and compulsions. Meaningful changes in anxiety and depression were also reported. Neuroimaging analysis of electrodes revealed that responders had more dorsally positioned active contacts relative to the NAc target. Insight emerged as a significant predictor of symptom improvement over time [2]. Qualitative findings revealed profound shifts in self-perception, agency, and cognitive appraisal of intrusive thoughts, supporting a mechanistic model in which DBS facilitates adaptive restructuring of obsessional beliefs [3]. These multi-level changes were synthesised into a staged framework of recovery and a set of actionable clinical recommendations [4]. Notably, adjunct cognitive behavioural therapy was experienced as critical in augmenting and consolidating DBS induced benefits.

Discussion: This work advances DBS for OCD beyond symptom reduction, highlighting its capacity to induce meaningful neurocognitive and psychosocial transformation. While also advocating for greater access to care and more patient centred approaches [5-7]. By integrating clinical, neuroimaging, and phenomenological data, we propose a precision medicine framework that refines patient selection, optimises targeting, and enhances therapeutic outcomes. Despite strong evidence, access to DBS for OCD remains limited. Our findings support its recognition as an established intervention for TR-OCD and underscore the need for broader implementation within multidisciplinary, circuit-informed care models.

References

1. Acevedo, N., et al., Therapeutic Neurostimulation in Obsessive-Compulsive and Related Disorders: A Systematic Review. Brain Sciences, 2021. 11(7): p. 948.
2. Acevedo, N., et al., Clinical outcomes of deep brain stimulation for obsessive‐compulsive disorder: insight as a predictor of symptom changes. Psychiatry and Clinical Neurosciences, 2023.
3. Acevedo, N., et al., Phenomenological Changes Associated with Deep Brain Stimulation for Obsessive Compulsive Disorder: A Cognitive Appraisal Model of Recovery. Brain Sciences, 2023. 13(10): p. 1444.
4. Acevedo, N., et al., Clinical recommendations for the care of people with treatment-refractory obsessive-compulsive disorder when undergoing deep brain stimulation. Australian & New Zealand Journal of Psychiatry, 2022. 0(0): p. 00048674221100947.
5. Acevedo, N., D. Castle, and S. Rossell, The promise and challenges of transcranial magnetic stimulation and deep brain stimulation as therapeutic options for obsessive-compulsive disorder. Expert Review of Neurotherapeutics, 2024. 24(2): p. 145–158.
6. Acevedo, N., et al., Call to revise the Royal Australian and New Zealand College of Psychiatrists’ clinical memorandum on deep brain stimulation for obsessive-compulsive disorder. Australian & New Zealand Journal of Psychiatry, 2023: p. 00048674231184410.
7. Acevedo, N. and S. Rossell, Deep brain stimulation for treatment-refractory obsessive-compulsive disorder should be an accepted therapy in Australia. Australian & New Zealand Journal of Psychiatry, 2021. 0(0): p. 00048674211049344.