Refractory Obsessive-compulsive Disorder Research Articles

White matter changes after Gamma Knife Capsulotomy in patients with intractable obsessive-compulsive disorder

BackgroundAnterior capsulotomy is one of the therapeutic options for refractory obsessive–compulsive disorder (OCD). Safety and efficacy of Gamma Knife Capsulotomy (GKC) have been demonstrated in the past. ObjectiveTo characterize changes induced by GKC using a fixel-based analysis (FBA) and possible predictors of efficacy. MethodsPatients with OCD refractory to other therapies underwent bilateral GKC with 120 Gy as a maximum dose on the anterior limb of the internal capsule (ALIC). The clinical outcome was percent reduction in Yale- Brown Obsessive–Compulsive Scale (Y-BOCS). White Matter changes were analyzed using fixel-based analysis (FBA) for fibre density (FD), fibre-bundle cross-section (FC) and the combination of the two (FDC). ResultsSeven patients underwent GKC. Median follow-up was 13 months (range 12–58 months). Mean (±SD) decrease in Y-BOCS score at last follow-up was 61 % ± 35 % with five patients considered as responders. FBA showed a symmetric FD reduction in the ALIC with extension to the anterior fronto-thalamic radiation; a reduction of FC along the superior longitudinal fasciculus (SLF) in both hemispheres with a predominance in the left one. Reductions in FDC were detected predominantly in the right hemisphere, with a similar pattern to FD reductions and associated with a positive correlation (p < 0.05) between Y-BOCS reduction and fibres passing in the ventral part. ConclusionsGKC is safe and efficient in reducing OCD severity in selected patients. Changes induced in white matter by GKC extend over the ALIC. Reduction of fibres passing the ventral part of the right sided ALIC correlates with better results.

Treating refractory obsessive compulsive disorder with cathodal transcranial direct current stimulation over the supplementary motor area: a large multisite randomized sham-controlled double-blind study.

The present study evaluated the therapeutic efficacy and tolerability of 10 transcranial direct current stimulation (tDCS) sessions in treatment-resistance obsessive-compulsive disorder (OCD) patients using a multisite double-blind sham-controlled design. Eighty treatment-resistance outpatients suffering from obsessive-compulsive disorder were randomized to receive either active or sham transcranial direct current stimulation. The cathode was positioned over the supplementary motor area and the anode over the right supraorbital area. Patients were evaluated at baseline, end of treatment (day 14), one-month follow-up (day 45), and three-month follow-up (day 105) on the Yale-Brown Obsessive Compulsive Scale. Although a significant interaction between time and treatment was observed, the primary endpoint-measuring the change in Yale-Brown obsessive compulsive scale scores after two weeks-was not achieved. Conversely, the secondary endpoint, which concerned the change in Yale-Brown obsessive compulsive scale scores after three months, was successfully met. It is important to note, however, that there were no significant differences in the percentage of responders and remitters at any of the post-treatment assessments. This suggests that the treatment may not have had a clinically relevant impact. Patients well received the transcranial direct current stimulation treatment, indicating its good tolerability. This is the largest controlled trial using transcranial direct current stimulation in treatment-resistance obsessive-compulsive disorder patients. Our results indicate the importance of studying the placebo effect in transcranial direct current stimulation and the necessity to consider a long follow-up time to best evaluate the effects of the intervention. ClinicalTrials.gov, identifier NCT03304600.

State-dependent effects of repetitive transcranial magnetic stimulation on symptom dimensions of obsessive-compulsive disorder: A case report

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation procedure that is FDA-cleared for treating obsessive-compulsive disorder (OCD). Evidence suggests that controlling brain state during rTMS treatment can influence treatment outcomes. We present the case of a patient with refractory OCD who received symptom provocation immediately preceding rTMS treatment sessions. The patient experienced more subjective and objective improvement in OCD symptoms targeted by provocations than in other symptom domains. These results suggest the importance of brain state during rTMS and could be used to guide and optimize neuromodulation treatment for OCD.

Severe Refractory Obsessive Compulsive Disorder and Depression: Should We Consider Stereotactic Neurosurgery?

Functional neurosurgery involves modulation of activity within neural circuits that drive pathological activity. Neurologists and neurosurgeons have worked closely together, advancing the field for over a century, such that neurosurgical procedures for movement disorders are now accepted as "standard of care", benefiting hundreds of thousands of patients. As with movement disorders, some neuropsychiatric illnesses, including obsessive compulsive disorder and depression, can be framed as disorders of neural networks. Over the past two decades, evidence has accumulated that stereotactic neurosurgery can help some patients with mental disorders. Nevertheless, despite the availability of class I evidence for some interventions, there is a huge mismatch between the prevalence of severe refractory mental disorders and the number of referrals made to specialised functional neurosurgery services. This paper examines the historical trajectory of neurosurgery for movement and mental disorders. A review of neurosurgical techniques, including stereotactic radiofrequency ablation, gamma knife, deep brain stimulation, and magnetic resonance imaging guided focused ultrasound, explains the high degree of safety afforded by technological advances in the field. Evidence from clinical trials supporting functional neurosurgery for mental disorders, including obsessive compulsive disorder and depression, is presented. An improved understanding of modern functional neurosurgery should foster collaboration between psychiatry and neurosurgery, providing hope to patients whose symptoms are refractory to all other treatments.

Diffusion Magnetic Resonance Imaging Tractography Guides Investigation of the Zona Incerta: A Novel Target for Deep Brain Stimulation

BackgroundThe zona incerta (ZI) is a subcortical structure primarily investigated in rodents that is implicated in various behaviors, ranging from motor control to survival-associated activities, partly due to its integration in multiple neural circuits. In the current study, we used diffusion magnetic resonance imaging tractography to segment the ZI and gain insight into its connectivity in various circuits in humans. MethodsWe performed probabilistic tractography in 7T diffusion MRI on 178 participants from the Human Connectome Project to validate the ZI’s anatomical subdivisions and their respective tracts. K-means clustering segmented the ZI based on each voxel’s connectivity profile. We further characterized the connections of each ZI subregion using probabilistic tractography with each subregion as a seed. ResultsWe identified 2 dominant clusters that delineated the whole ZI into rostral and caudal subregions. The caudal ZI primarily connected with motor regions, while the rostral ZI received a topographic distribution of projections from prefrontal areas, notably the anterior cingulate and medial prefrontal cortices. We generated a probabilistic ZI atlas that was registered to a patient-participant’s magnetic resonance imaging scan for placement of stereoencephalographic leads for electrophysiology-guided deep brain stimulation to treat their obsessive-compulsive disorder. Rostral ZI stimulation improved the patient’s core symptoms (mean improvement 21%). ConclusionsWe present a tractography-based atlas of the rostral and caudal ZI subregions constructed using high-resolution diffusion magnetic resonance imaging from 178 healthy participants. Our work provides an anatomical foundation to explore the rostral ZI as a novel target for deep brain stimulation to treat refractory obsessive-compulsive disorder and other disorders associated with dysfunctional reward circuitry.

Safety, feasibility, tolerability, and clinical effects of repeated psilocybin dosing combined with non-directive support in the treatment of obsessive-compulsive disorder: protocol for a randomized, waitlist-controlled trial with blinded ratings.

To date, few randomized controlled trials of psilocybin with non-directive support exist for obsessive-compulsive disorder (OCD). Results and participant feedback from an interim analysis of an ongoing single-dose trial (NCT03356483) converged on the possibility of administering a higher fixed dose and/or more doses of psilocybin in future trials for presumably greater benefits. This trial aims to evaluate the safety, feasibility, tolerability, and clinical effects of two doses of psilocybin paired with non-directive support in the treatment of OCD. This trial also seeks to examine whether two doses of psilocybin lead to greater OCD symptom reduction than a single dose, and to elucidate psychological mechanisms underlying the effects of psilocybin on OCD. A randomized (1:1), waitlist-controlled design with blinded ratings will be used to examine the effects of two doses of oral psilocybin paired with non-directive support vs. waitlist control on OCD symptoms. An adaptive dose selection strategy will be implemented (i.e., first dose: 25 mg; second dose: 25 or 30 mg). This single-site trial will enroll 30 adult participants with treatment-refractory OCD. Aside from safety, feasibility, and tolerability metrics, primary outcomes include OCD symptoms assessed on the Yale-Brown Obsessive-Compulsive Scale - Second Edition (Y-BOCS-II). A blinded independent rater will assess primary outcomes at baseline and the primary endpoint at the end of the second dosing week. Participants will be followed up to 12 months post-second dosing. Participants randomized to waitlist will be rescreened after 7 weeks post-randomization, and begin their delayed treatment phase thereafter if still eligible. Written informed consent will be obtained from participants. The institutional review board has approved this trial (protocol v. 1.7; HIC #2000032623). This study seeks to advance our ability to treat refractory OCD, and catalyze future research seeking to optimize the process of psilocybin treatment for OCD through understanding relevant psychological mechanisms.Clinical trial registration: ClinicalTrials.gov, identifier NCT05370911.

Electroconvulsive Therapy in Treatment Resistant Obsessive-Compulsive Disorder: A Case Report

Obsessive-compulsive disorder (OCD) is characterized by the presence of obsessions, compulsions, or both, which is time consuming and causes significant functional impairment. The treatment options for obsessive-compulsive disorder include medication and psychological therapy. Electroconvulsive therapy (ECT) stands as an effective treatment for severe and treatment-resistant psychiatric conditions. However, there is still insufficient evidence regarding the efficacy of ECT in OCD. We intend to report a case of a middle-aged woman who suffered from severe and refractory OCD who showed promising response following her ECT. Patient showed symptoms of relapse one month after the completion of ECT which led to the re-initiation of another acute series of ECT. Despite achieving improvement in symptoms, the patient experienced a distressing post ECT delirium. Even though the delirium was resolved after one week, the patient was not keen to continue with ECT. ECT emerges as both a safe and effective option for severe and refractory OCD, particularly in cases where conventional treatments prove ineffective. As of yet, the exact mechanism of how ECT works is unexplained, and the value of ECT in OCD should be further investigated.

Deep brain stimulation-related experiences for obsessive-compulsive disorder: In-depth interviews with operated patients and relatives

BackgroundDeep brain stimulation (DBS) is an effective intervention for refractory obsessive-compulsive disorder (OCD). Although treatment success is measured by a decrease in the severity of core symptoms, this procedure can have broader psychological and physical effects. The field regrettably still lacks knowledge and tools allowing an adequate understanding and assessment of the full range of experiences that accompany DBS treatment. We aimed to describe possible side effects of DBS treatment as experienced by patients, beyond specific changes in OCD core symptoms. MethodsWe interviewed 16 patients and 7 of their relatives from two independent cohorts, receiving stimulation in different anatomical locations. We conducted semi-structured interviews, then transcribed at verbatim. Inductive content analysis was performed to code and group common themes. ResultsWe categorized a variety of psychological and physical experiences. Patients frequently reported long-lasting changes often manifesting as improved mood and calmer behavior, but also as impaired memory, concentration, and sleep problems. Further, a wide range of individual experiences were described, suggesting that patients can feel and behave significantly different towards themselves and others, feeling more sensitive, more or less emotional, more impulsive, more irritable, more talkative. ConclusionsWe stress the importance of accumulating knowledge of the full range of DBS-related experiences, to improve shared decision making between patients and treating clinicians, and to facilitate comprehensive monitoring throughout the course of treatment.

Clinical outcomes of deep brain stimulation for obsessive-compulsive disorder: Insight as a predictor of symptom changes.

Deep brain stimulation (DBS) is a safe and effective treatment option for people with refractory obsessive-compulsive disorder (OCD). Yet our understanding of predictors of response and prognostic factors remains rudimentary, and long-term comprehensive follow-ups are lacking. We aim to investigate the efficacy of DBS therapy for OCD patients, and predictors of clinical response. Eight OCD participants underwent DBS stimulation of the nucleus accumbens (NAc) in an open-label longitudinal trial, duration of follow-up varied between 9 months and 7 years. Post-operative care involved comprehensive fine tuning of stimulation parameters and adjunct multidisciplinary therapy. Six participants achieved clinical response (35% improvement in obsessions and compulsions on the Yale Brown Obsessive Compulsive Scale (YBOCS)) within 6-9 weeks, response was maintained at last follow up. On average, the YBOCS improved by 45% at last follow up. Mixed linear modeling elucidated directionality of symptom changes: insight into symptoms strongly predicted (P = 0.008) changes in symptom severity during DBS therapy, likely driven by initial changes in depression and anxiety. Precise localization of DBS leads demonstrated that responders most often had their leads (and active contacts) placed dorsal compared to non-responders, relative to the Nac. The clinical efficacy of DBS for OCD is demonstrated, and mediators of changes in symptoms are proposed. The symptom improvements within this cohort should be seen within the context of the adjunct psychological and biopsychosocial care that implemented a shared decision-making approach, with flexible iterative DBS programming. Further research should explore the utility of insight as a clinical correlate of response. The trial was prospectively registered with the ANZCTR (ACTRN12612001142820).

Neuroablative Intervention for Refractory Obsessive-Compulsive Disorder.

This review aims to investigate the progression of neuroablation, along with documented clinical efficacy and safety, in the management of treatment-resistant obsessive-compulsive disorder (OCD). We searched and compiled clinical research results of neuroablation therapy reported to date. We extracted outcomes related to clinical efficacy, side effects, and surgical complications. Additionally, we summarized key claims and findings. Neuroablative intervention is a potential treatment approach for refractory OCD. Recent advancements, such as real-time magnetic resonance monitoring and minimally invasive techniques employing ultrasound and laser, offer distinct advantages in terms of safety and comparative efficacy when compared to conventional methods. However, the absence of randomized controlled trials and long-term outcome data underscores the need for cautious consideration when selecting neuroablation. Neuroablative intervention shows promise for refractory OCD, but vigilant consideration is essential in both patient selection and surgical method choices due to the potential for rare yet serious complications.

Anterior Capsulotomy for Refractory Obsessive-Compulsive Disorder: A Tractography and Lesion Geometry study

Introduction: A bilateral anterior capsulotomy effectively treats refractory obsessive-compulsive disorder (OCD). We investigated the geometry of lesions and disruption of white matter pathways within the anterior limb of the internal capsule (ALIC) in patients with different outcomes. Methods: In this retrospective study, we analyzed data from 18 patients with refractory OCD who underwent capsulotomies. Patients were grouped into “responders” and “nonresponders” based on the percentage of decrease in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) after surgery. We investigated neurobehavioral adverse effects and analyzed the overlap between lesions and the ventromedial prefrontal (vmPFC) and dorsolateral prefrontal (dlPFC) pathways. Probabilistic maps were constructed to investigate the relationship between lesion location and clinical outcomes. Results: Of the 18 patients who underwent capsulotomies, 12 were responders (>35% improvement in YBOCS), and six were nonresponders. The vmPFC pathway was more involved than the dlPFC pathway in responders (p = 0.01), but no significant difference was observed in nonresponders (p = 0.10). The probabilistic voxel-wise efficacy map showed a relationship between ventral voxels within the ALIC with symptom improvement. Weight gains occurred in 11/18 (61%) patients and could be associated with medial voxels within the ALIC. Conclusion: The optimal outcome after capsulotomy in refractory OCD is linked to vmPFC disruption in the ALIC. Medial voxels within the ALIC could be associated with weight gains following capsulotomy.

61 Increased Apathy Post-Laser Ablation for Refractory Obsessive-Compulsive Disorder

Objective:Severe OCD is often nonresponsive to pharmacological and behavioral therapies and thus surgical interventions are emerging. Surgical interventions have proven to be efficacious for treating refractory OCD, however limited publications suggest 22–40% of patients experience transient apathy and disinhibition post-surgery (McLaughlin et al., 2021). Apathy is highly associated with the same brain regions, the prefrontal cortex, striatum, and thalamus, which have also been implicated in OCD symptoms (Le Heron et al., 2018). Prior research noting post-surgical changes in apathy in OCD either used physician observations or less precise surgical methods (i.e., gamma knife or radiofrequency ablation). Apathy has also been highly associated with depression and executive dysfunction (Raffard et al, 2020) and often not co-assessed in prior studies. The newest intervention, cutting-edge MR-guided laser interstitial thermal therapy (LITT), limits damage outside the region of interest by precise control of thermal application in real-time. Thus, the current case series aims to investigate objective patient-reported change in apathy, disinhibition, depression, and executive dysfunction following anterior capsulotomy via this newest surgical approach for OCD.Participants and Methods:In this retrospective study, the responses of ten consecutive patients pre- and post-LITT on the following measures were examined: Frontal Systems Behavior Scale (FrSBe), Beck Depression Inventory-II (BDI-II), and Yale Brown Obsessive-Compulsive Scale (Y-BOCS). Reliable Change Index (RCI) was used to evaluate meaningful change in pre- and post-LITT self-reported levels of apathy, disinhibition, executive dysfunction, along with depressive symptoms. Per prior published guidelines, patient-reported Y-BOCS (range 0–40) scores were used to measure OCD symptoms with 24–34 % score reduction representing partial and 35% or greater score reduction representing full response (Pepper et al., 2019).Results:Seven patients (70%) were male, with a sample mean age of 38.4 (SD=13.6) and a mean of 14.6 (SD =2.27) years of education. Mean Y-BOCS score decreased from 32 (SD=5.3) before surgery to 18.8 (SD=11.1) after. Over 65% had partial or full response in OCD symptoms post-surgery. Six patients endorsed increased apathy, with others endorsing no change. Half of the non-responders reported this increase in apathy. The cohort remained relatively stable in disinhibition and executive dysfunction. Over half the cohort demonstrated a significant decrease in depressive symptoms. Interestingly, two of the non-responders and one responder endorsed increased apathy despite stable or improving depressive symptoms, disinhibition, and executive dysfunction.Conclusions:Surgical interventions for psychiatric disorders are emerging quickly and being refined daily. In this cohort, anterior capsulotomy via LITT provided full or partial OCD recovery for most patients. However, most patients reported significant increases in apathy, despite experiencing a decrease in depressive symptoms, with stable disinhibition and executive dysfunction. Despite these promising improvements in OCD symptomatology via LITT, impact of surgery on apathy levels is clearly warranted using objective, quantifiable methods. As apathy has consistently been related to functional impairment and poorer quality of life, understanding this outcome is imperative in larger trials. Better understanding of this finding and underlying circuity will allow patients to be fully informed regarding this promising surgical intervention.

Use of differential stimulation of the nucleus accumbens and anterior limb of the internal capsule to improve outcomes of obsessive-compulsive disorder.

Personalized stimulation is key to optimizing the outcomes of deep brain stimulation (DBS) for refractory obsessive-compulsive disorder (OCD). However, the contacts in a single conventional electrode cannot be programmed independently, which may affect the therapeutic efficacy of DBS for OCD. Therefore, a novel designed electrode and implantable pulse generator (IPG) that could achieve differential stimulation parameters for different contacts was implanted into the nucleus accumbens (NAc) and anterior limb of the internal capsule (ALIC) of a cohort of patients with OCD. Thirteen consecutive patients underwent bilateral DBS of the NAc-ALIC between January 2016 and May 2021. Differential stimulation of the NAc-ALIC was applied at initial activation. Primary effectiveness was assessed on the basis of change in scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) from baseline to 6-month follow-up. Full-response was defined as a 35% decrease in Y-BOCS score. Secondary effectiveness measures were the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). The local field potential of bilateral NAc-ALIC was recorded in 4 patients who were reimplanted with a sensing IPG after battery depletion of the previous IPG. The Y-BOCS, HAMA, and HAMD scores decreased remarkably during the first 6 months of DBS. Ten of 13 patients were categorized as responders (76.9%). Differential stimulation of the NAc-ALIC was favorable to optimization of the stimulation parameters by increasing the parameter configurations. Power spectral density analysis revealed pronounced delta-alpha frequency activity in the NAc-ALIC. Phase-amplitude coupling of the NAc-ALIC showed that strong coupling is present between the phase of delta-theta and broadband gamma amplitude. These preliminary findings indicate that differential stimulation of the NAc-ALIC can improve the efficacy of DBS for OCD. Clinical trial registration no.: NCT02398318 (ClinicalTrials.gov).

Perspectives on informed assent and bodily integrity in prospective deep brain stimulation for youth with refractory obsessive-compulsive disorder

Background Deep brain stimulation is approved for treating refractory obsessive-compulsive disorder in adults under the US Food and Drug Administration Humanitarian Device Exemption, and studies have shown its efficacy in reducing symptom severity and improving quality of life. While similar deep brain stimulation treatment is available for pediatric patients with dystonia, it is not yet available for pediatric patients with obsessive-compulsive disorder, although soon could be. The prospect of growing indications for pediatric deep brain stimulation raises several ethical concerns relating to bodily integrity, the ability to offer informed assent, and the role pediatric patients play in the decision-making process. Objective The aim of this study is to solicit and assess the views of stakeholders (children, parents, clinicians) on pediatric assent, autonomy, and bodily integrity in the context of potential pediatric deep brain stimulation for obsessive-compulsive disorder. Methods Semi-structured interviews were conducted with pediatric obsessive-compulsive disorder patients ( n = 21), caregivers of pediatric obsessive-compulsive disorder patients aged 14–18 ( n = 19), and clinicians with experience treating refractory obsessive-compulsive disorder ( n = 25). Interviews were transcribed and coded in MAXQDA 2018 and 2020 software and processed for thematic content analysis to isolate and compare specific themes. Results A majority of respondents (74%, 48/65) across all three stakeholder groups voiced that the decision-making process should be collaborative and involve everyone (clinicians: 84% or 21/25, caregivers 71% or 15/21, and patients 63% or 12/19). We identified a split between respondents’ views on who should have the final say in the event of disagreement (38% or 25/65 favored the patient versus 35% or 23/65 favoring caregivers). A split between respondents also emerged concerning the maturity relevant for deep brain stimulation decision-making, with 45% (29/65) favoring developmental maturity (age/physiological development) and 45% (29/65) favoring decisional maturity (capacity to understand and weigh information). A majority of clinicians indicated that they would not move forward with deep brain stimulation without securing patient assent (80% or 20/25), with some stating the only exception is if patient quality of life was very poor and/or they lacked insight. Both caregivers and patients expressed a significant respect for the patient's right to bodily integrity, with 67% of caregivers (14/21) and 68% of patients (13/19) justifying patient involvement in decision-making specifically with reference to infringements of bodily integrity. Conclusion Our findings demonstrate that despite broad agreement across stakeholders that the decision-making process for pediatric deep brain stimulation for obsessive-compulsive disorder should be collaborative and somehow involve pediatric patients, there is disagreement about what this process entails and what factors determine patient involvement in the process. However, there is agreement that children have a right to bodily and brain integrity, which should only be infringed upon in rare circumstances.

A Systematic Review on Comparison of Deep Brain Stimulation (DBS) and Transcranial Magnetic Stimulation (TMS) in the Treatment of Refractory Obsessive Compulsive Disorder (OCD)

The Diagnostic and Statistical Manual of mental disorders (DSM 4) defines obsessive compulsive disorder (OCD) as compulsive or repetitive behaviors of obsessions that a person feels driven to perform. These acts and behaviors are aimed at preventing or reducing distress but are not connected in a realistic way. OCD is a pathological hypothesis of dysfunctions occurring within the cortico-striato-thalamo-cortical loops. It is one of the most prevalent and disabling psychiatric disorder associated with decreased life quality (American Psychiatric Association). This article will provide a brief study on the comparison of deep brain stimulation and transcranial magnetic stimulation in the treatment of refractory obsessive compulsive disorder besides other pharmacological and non-pharmacological treatments.&#x0D; Keywords: OCD, Deep brain stimulation, Transcranial magnetic stimulation

Deep Brain Stimulation Surgery Programs in Canada

&#x0D; Deep brain stimulation involves the surgical insertion of electrodes to stimulate targeted areas of the brain. It is recommended to help control movement-related symptoms of Parkinson disease with certain indications and contraindications to consider.&#x0D; This rapid Environmental Scan describes the landscape of deep brain stimulation surgery across Canada and identifies conditions other than Parkinson disease that can benefit from the therapy. It also provides an overview of cost-effectiveness studies on deep brain stimulation for Parkinson disease.&#x0D; Emerging indications for deep brain stimulation include refractory obsessive-compulsive disorder, refractory epilepsy, treatment-resistant Tourette syndrome, certain types of pain, refractory major depressive disorder, tardive dyskinesia, and essential tremor.&#x0D; In Canada, there are deep brain stimulation surgery programs in Alberta, British Columbia, Manitoba, Nova Scotia, Ontario, Quebec, and Saskatchewan. The number of qualified neurosurgeons for deep brain stimulation surgery ranges from 1 to 5 (at least) across jurisdictions.&#x0D; Overall, deep brain stimulation is considered cost-effective for people living with advanced Parkinson disease. The risk of developing Parkinson disease increases with age, with onset typically occurring in late adulthood. The number of people eligible for deep brain stimulation in Canada is expected to increase with the aging population and emerging indications. Information related to existing surgery programs can help support capacity planning for deep brain stimulation surgery in Canada.&#x0D;

Memantine for Refractory Obsessive-Compulsive Disorder: Protocol for a Pragmatic, Double-blind, Randomized, Parallel-Group, Placebo-Controlled, Monocenter Trial

Obsessive-compulsive disorder (OCD) is a psychiatric syndrome characterized by unwanted and repetitive thoughts and repeated ritualistic compulsions for decreasing distress. Symptoms can cause severe distress and functional impairment. OCD affects 2% to 3% of the population and is ranked within the 10 leading neuropsychiatric causes of disability. Cortico-striatal-thalamo-cortical circuitry dysfunction has been implicated in OCD, including altered brain activation and connectivity. Complex glutamatergic signaling dysregulation within cortico-striatal circuitry has been proposed in OCD. Data obtained by several studies indicate reduced glutamatergic concentrations in the anterior cingulate cortex, combined with overactive glutamatergic signaling in the striatum and orbitofrontal cortex. A growing number of randomized controlled trials have assessed the utility of different glutamate-modulating drugs as augmentation medications or monotherapies for OCD, including refractory OCD. However, there are relevant variations among studies in terms of patients' treatment resistance, comorbidity, age, and gender. At present, 4 randomized controlled trials are available on the efficacy of memantine as an augmentation medication for refractory OCD. Our study's main purpose is to conduct a double-blind, randomized, parallel-group, placebo-controlled, monocenter trial to assess the efficacy and safety of memantine as an augmentative agent to a selective serotonin reuptake inhibitor in the treatment of moderate to severe OCD. The study's second aim is to evaluate the effect of memantine on cognitive functions in patients with OCD. The third aim is to investigate if responses to memantine are modulated by variables such as gender, symptom subtypes, and the duration of untreated illness. Investigators intend to conduct a double-blind, randomized, parallel-group, placebo-controlled, monocenter trial to assess the efficacy and safety of memantine as an augmentative agent to a selective serotonin reuptake inhibitor in the treatment of patients affected by severe refractory OCD. Participants will be rated via the Yale-Brown Obsessive Compulsive Scale at baseline and at 2, 4, 6, 8, 10, and 12 months. During the screening period and T4 and T6 follow-up visits, all participants will undergo an extensive neuropsychological evaluation. The 52-week study duration will consist of 4 distinct periods, including memantine titration and follow-up periods. Recruitment has not yet started. The study will be conducted from June 2023 to December 2024. Results are expected to be available in January 2025. Throughout the slow-titration period, we will observe the minimum effective dose of memantine, and the follow-up procedure will detail its residual efficacy after drug withdrawal. The innovation of this research proposal is not limited to the evaluation of the efficacy and safety of memantine as an augmentation medication for OCD. We will also test if memantine acts as a pure antiobsessive medication or if memantine's ability to improve concentration and attention mimics an antiobsessive effect. ClinicalTrials.gov NCT05015595; https://clinicaltrials.gov/ct2/show/NCT05015595. PRR1-10.2196/39223.

Patient feedback and psychosocial outcomes of deep brain stimulation in people with obsessive–compulsive disorder

Severe and refractory psychiatric patients can experience complex and profound changes in symptomology, functioning and well-being from deep brain stimulation (DBS) therapy. Currently, the efficacy of DBS is assessed by clinician rated scales of primary symptoms, yet this does not capture the multitude of DBS mediated changes or represent the patient perspective. We aimed to elucidate the patient perspective in psychiatric DBS application by investigating 1) symptomatic, and 2) psychosocial changes, 3) therapeutic expectations and satisfaction, 4) decision-making capacity, and 5) clinical care recommendations from treatment refractory obsessive–compulsive disorder (OCD) DBS patients. Participants enrolled in an open label clinical trial of DBS therapy for OCD who had reached clinical response were invited to participate in a follow up survey. Participants completed a 1) feedback survey relating to goals, expectations, and satisfaction of therapy, and 2) self-report questionnaires on psychosocial functioning including quality of life, cognitive insight, locus of control, rumination, cognitive flexibility, impulsivity, affect, and well-being. Greatest change was reported for quality of life, rumination, affect and cognitive flexibility. Participants reported realistic expectations, high satisfaction, adequate pre-operative education and decision-making capacity; and advocated for greater access to DBS care and more widespread support services. This is the first identified investigation on psychiatric patient perspectives of functioning and therapeutic outcomes following DBS. Insights from the study have implications for informing psychoeducation, clinical practices, and neuroethical debates. We encourage a greater patient-centred and biopsychosocial approach in evaluating and managing OCD DBS patients, by considering personally meaningful goals and addressing symptomatic and psychosocial recovery.

Gamma knife capsulotomy for intractable OCD: Neuroimage analysis of lesion size, location, and clinical response

Obsessive-compulsive disorder (OCD) affects 2–3% of the population. One-third of patients are poorly responsive to conventional therapies, and for a subgroup, gamma knife capsulotomy (GKC) is an option. We examined lesion characteristics in patients previously treated with GKC through well-established programs in Providence, RI (Butler Hospital/Rhode Island Hospital/Alpert Medical School of Brown University) and São Paulo, Brazil (University of São Paolo). Lesions were traced on T1 images from 26 patients who had received GKC targeting the ventral half of the anterior limb of the internal capsule (ALIC), and the masks were transformed into MNI space. Voxel-wise lesion-symptom mapping was performed to assess the influence of lesion location on Y-BOCS ratings. General linear models were built to compare the relationship between lesion size/location along different axes of the ALIC and above or below-average change in Y-BOCS ratings. Sixty-nine percent of this sample were full responders (≥35% improvement in OCD). Lesion occurrence anywhere within the targeted region was associated with clinical improvement, but modeling results demonstrated that lesions occurring posteriorly (closer to the anterior commissure) and dorsally (closer to the mid-ALIC) were associated with the greatest Y-BOCS reduction. No association was found between Y-BOCS reduction and overall lesion volume. GKC remains an effective treatment for refractory OCD. Our data suggest that continuing to target the bottom half of the ALIC in the coronal plane is likely to provide the dorsal–ventral height required to achieve optimal outcomes, as it will cover the white matter pathways relevant to change. Further analysis of individual variability will be essential for improving targeting and clinical outcomes, and potentially further reducing the lesion size necessary for beneficial outcomes.

Safety, tolerability, and clinical and neural effects of single-dose psilocybin in obsessive-compulsive disorder: protocol for a randomized, double-blind, placebo-controlled, non-crossover trial.

Psilocybin may help treat obsessive-compulsive disorder (OCD). To date, only one open-label study of psilocybin for OCD exists, necessitating further investigation with a randomized controlled design. The neural correlates of psilocybin's effects on OCD have also not been studied. This first-of-its-kind trial aims to evaluate the feasibility, safety, and tolerability of psilocybin in the treatment of OCD, provide preliminary evidence on the effects of psilocybin on OCD symptoms, and elucidate neural mechanisms that may mediate psilocybin's effects on OCD. We use a randomized (1:1), double-blind, placebo-controlled, non-crossover design to examine the clinical and neural effects of either a single dose of oral psilocybin (0.25 mg/kg) or active placebo-control agent (250 mg of niacin) on OCD symptoms. We are enrolling 30 adult participants at a single site in Connecticut, USA who have failed at least one trial of standard care treatment (medication/psychotherapy) for OCD. All participants will also receive unstructured, non-directive psychological support during visits. Aside from safety, primary outcomes include OCD symptoms over the past 24 h, assessed by the Acute Yale-Brown Obsessive-Compulsive Scale and Visual Analog Scale ratings. These are collected by blinded, independent raters at baseline and the primary endpoint of 48 h post-dosing. Total follow-up is 12 weeks post-dosing. Resting state neuroimaging data will be collected at baseline and primary endpoint. Participants randomized to placebo will be offered the chance to return for an open-label dose of 0.25 mg/kg. All participants will be required to provide written informed consent. The trial (protocol v. 5.2) was approved by the institutional review board (HIC #2000020355) and registered with ClinicalTrials.gov (NCT03356483). This study may represent an advance in our ability to treat refractory OCD, and pave the way for future studies of neurobiological mechanisms of OCD that may respond to psilocybin.