Treatment-resistant Obsessive-compulsive Disorder Research Articles

The Effectiveness of Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is an anxiety-related disorder. Obsessions are experienced as recurring, unwanted thoughts. In response to obsessions, people feel driven to act with repetitive behaviours, known as compulsions. Obsessions and compulsions cause significant distress and impairment in an individual’s daily life and relationships. OCD is relatively common, with a lifetime prevalence rate between 2%-3%. Thus, research must find an effective treatment for individuals with OCD. This paper examines a relatively new area of research that explores the use of transcranial magnetic stimulation (TMS) to treat OCD. TMS is a non-invasive brain stimulation that has recently shown promising effects in treating psychological disorders. Studies researching TMS on OCD, primarily with individuals who have not responded to previous treatments, have found it to be effective, with symptoms significantly decreasing post-treatment, and with effects lasting up to 3-months post-treatment. Overall, TMS appears to offer an effective alternative for individuals with treatment-resistant OCD. However, while studies on TMS show significant results, participants with greater OCD symptoms and/or sleep disturbances tend to report a decreased response to treatment. Also, studies using TMS typically have limitations with their sample sizes, lack of control groups, and lack of long-term follow-up assessments. Overall, TMS appears to be effective for OCD, but future research needs to address current limitations to determine the true effectiveness of this new treatment.

Esketamine Augmentation in Treatment-Resistant Obsessive-Compulsive Disorder: A Retrospective Chart Review.

Converging evidence supports the role of the glutamate, an excitatory amino acid neurotransmitter, in the pathophysiology of obsessive-compulsive disorder (OCD). Ketamine and esketamine, both noncompetitive N -methyl- d -aspartate antagonists, have emerged as a promising medication for this psychiatric disorder, given its possible efficacy with faster onset and good tolerability. The purpose of this retrospective chart review is to evaluate whether unbiased clinical documentation supports formal clinical trials of esketamine for an OCD indication. A retrospective chart review of patients with treatment-resistant OCD receiving a single dose of esketamine (0.5mg/kg) added to standard therapy was conducted. The Yale-Brown Obsessive-Compulsive Scale and the Montgomery-Åsberg Depression Rating Scale were used to evaluate OCD and depressive symptoms respectively at baseline, 24 hours, and 7 days after esketamine administration. Descriptive statistics were used to analyze the data. Eight subjects were identified in this retrospective chart review: esketamine was administered subcutaneously in 7 and intravenously in 1. One week after infusion, 25% of the sample met criteria for treatment response and 50% for partial response. Major depressive disorder was a comorbid diagnosis in 75% of the sample and 2 of these subjects showed a positive antidepressant response. Our findings provide preliminary evidence that esketamine may reduce obsessive-compulsive symptoms in a subset of treatment-resistant OCD patients.

Agomelatine efficacy in treatment resistant obsessive-compulsive disorder: A randomized controlled trial.

Obsessive-compulsive disorder (OCD) is a prevalent and burdensome mental health condition, often resistant to conventional treatments. Agomelatine (Valdoxan), a compound acting on serotonin and melatonin systems, has shown promise in treating those with treatment-resistant OCD based on anecdotal reports and case studies. A randomized, double-blind controlled trial was conducted with 60 patients diagnosed with treatment-resistant OCD. Participants were randomized into an intervention group (receiving agomelatine 50 mg/day) and a control group (receiving placebo). OCD symptoms were assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) over a 12-week period. There were no significant differences in age, gender, or baseline Y-BOCS scores between intervention and control groups. Agomelatine did not demonstrate a significant improvement in OCD symptoms compared to placebo. Adverse events were comparable between groups, and liver enzyme levels remained within the normal range. This study, while not confirming superior efficacy compared to placebo, underscores the need for continued investigation into agomelatine's potential for treating specific subgroups of OCD patients, underscoring the need for more comprehensive and well-controlled trials in the future.

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.

Network Analysis for Predicting Treatment Response in Patients with Obsessive-Compulsive Disorder

Background: High resistance-to-treatment rates in obsessive-compulsive disorder (OCD) and various treatments remain significant obstacles to psychiatric disorder treatments. Objectives: The current study used network analysis to predict treatment response by psychiatric symptoms in the contamination/cleaning and danger/checking OCD subtypes. Methods: We evaluated 136 patients (mean age: 30.50 ± 5.25) who finished a 12-week selective serotonin reuptake inhibitor (SSRI) course. We used the convenience sampling method. All patients completed structured clinical interviews for the diagnostic and statistical manual of mental disorders, fifth edition research version (SCID-5-RV) at baseline and post-test. After treatment completion, the patients were categorized as responders and resistant according to their OCD severity scores (at the post-test). We used a network approach to determine the network structure of patients before and after the treatment. Network analysis was used by "the R programming language" to compare patterns of psychiatric symptoms. Additionally, we contrasted treatment-responsive patients' network structure with treatment-resistant OCD patients in each subtype. Results: In baseline, dysthymia, insomnia, binge eating, agoraphobia, and panic were the most central (important) nodes in the danger/checking subtype. However, hoarding, ADHD, insomnia, depression, and panic were the most central nodes in the contamination/cleaning group at baseline. Also, global strength and symptom connectivity were higher in the contamination/cleaning subtype than in the danger/check subtype (P < 0.05). In the contamination/cleaning subtype, "insomnia" was the most significant predictor for categorizing patients as resistant at the post-test. For contamination/cleaning, panic and binge eating played similar roles in treatment outcomes. Conclusions: Psychiatric symptoms can predict treatment responses in OCD subtypes. So, it is necessary to consider psychiatric comorbidities regarding OCD subtypes.

Responsive deep brain stimulation guided by ventral striatal electrophysiology of obsession durably ameliorates compulsion

Treatment-resistant obsessive-compulsive disorder (OCD) occurs in approximately one-third of OCD patients. Obsessions may fluctuate over time but often occur or worsen in the presence of internal (emotional state and thoughts) and external (visual and tactile) triggering stimuli. Obsessive thoughts and related compulsive urges fluctuate (are episodic) and so may respond well to a time-locked brain stimulation strategy sensitive and responsive to these symptom fluctuations. Early evidence suggests that neural activity can be captured from ventral striatal regions implicated in OCD to guide such a closed-loop approach. Here, we report on a first-in-human application of responsive deep brain stimulation (rDBS) of the ventral striatum for a treatment-refractory OCD individual who also had comorbid epilepsy. Self-reported obsessive symptoms and provoked OCD-related distress correlated with ventral striatal electrophysiology. rDBS detected the time-domain area-based feature from invasive electroencephalography low-frequency oscillatory power fluctuations that triggered bursts of stimulation to ameliorate OCD symptoms in a closed-loop fashion. rDBS provided rapid, robust, and durable improvement in obsessions and compulsions. These results provide proof of concept for a personalized, physiologically guided DBS strategy for OCD.

Lumateperone monotherapy for treatment-resistant obsessive-compulsive disorder in an adolescent.

Lumateperone monotherapy for treatment-resistant obsessive-compulsive disorder in an adolescent.

Deep brain stimulation for treatment resistant obsessive compulsive disorder; an observational study with ten patients under real-life conditions.

Obsessive-compulsive disorder (OCD) affects 2-3% of the global population, causing distress in many functioning levels. Standard treatments only lead to a partial recovery, and about 10% of the patients remain treatment-resistant. Deep brain stimulation offers a treatment option for severe, therapy-refractory OCD, with a reported response of about 60%. We report a comprehensive clinical, demographic, and treatment data for patients who were treated with DBS in our institution. We offered DBS to patients with severe chronic treatment resistant OCD. Severity was defined as marked impairment in functioning and treatment resistance was defined as non-response to adequate trials of medications and psychotherapy. Between 2020 and 2022, 11 patients were implanted bilaterally in the bed nucleus of stria terminalis (BNST). Patients were evaluated with YBOCS, MADRS, GAF, CGI, and WHOQOL-BREF. We performed the ratings at baseline (before surgery), after implantation before the start of the stimulation, after reaching satisfactory stimulation parameters, and at follow-up visits 3, 6, 9, and 12 months after optimized stimulation. One patient has retracted his consent to publish the results of his treatment, thus we are reporting the results of 10 patients (5 males, 5 females, mean age: 37 years). Out of our 10 patients, 6 have shown a clear response indicated by a YBOCS-reduction between 42 and 100 percent at last follow-up. One further patient experienced a subjectively dramatic effect on OCD symptoms, but opted afterwards to stop the stimulation. The other 3 patients showed a slight, non-significant improvement of YBOCS between 8.8 and 21.9%. The overall mean YBOCS decreased from 28.3 at baseline to 13.3 (53% reduction) at the last follow-up. The improvement of the OCD symptoms was also accompanied by an improvement of depressive symptoms, global functioning, and quality of life. Our results suggest that BNST-DBS can be effective for treatment-resistant OCD patients, as indicated by a reduction in symptoms and an overall improvement in functioning. Despite the need for additional research to define the patients' selection criteria, the most appropriate anatomical target, and the most effective stimulation parameters, improved patient access for this therapy should be established.

Neurosurgical Interventions for Umpteen Psychological Afflictions: a Substantial Cross-Disciplinary Clinical Abridged Frame of Reference

Purpose: Clinical society faces tremendous difficulties while treating people with mental illnesses, and the best possible care can only be provided by using an integrative approach to assessment and therapy. Particularly, the field of "psychosurgery," or the neurosurgical management of mental diseases, has piqued interest as a possible means of changing behavior and awareness throughout human history. In cases of severe refractory mental disease, psychological surgery - including "deep brain stimulation" and "stereotactic ablation" - is a key therapy option. Recent developments in neuroimaging, as well as psychosurgery, have increased the focus on these therapy techniques. In this paper, the benefits and drawbacks associated with psychological surgery will be thoroughly examined. Objective: The main objective of the paper is to aid individuals in understanding the basics of psychosurgery and its applications. Additionally, it focuses on how to remove the stigma associated with psychosurgery by providing reliable scientific data. Basic information and an overview were supplied thoroughly and simply to fulfill the aforementioned claim. In order to address the "psychosurgery versus psychopharmacology" debate, this paper focuses on analyzing information from many sources and outlining the core principles of each of these treatment modalities. Design/Methodology/Approach: Psychological surgery, which includes "deep brain stimulation as well as "stereotactic ablation," is a crucial treatment strategy in situations of severe refractory mental illness. The fact that several large studies have shown a median rate of response of approximately fifty percent highlights the importance of choosing and selecting participants beforehand. This concept has received attention as a result of recent developments in neurological imaging. Markers of reaction in scientific journals on neuroimaging in psychological operations have also been carefully investigated in order to evaluate the current state of knowledge for imaging prior to surgery. Scientific information was acquired for this research from a variety of trustworthy and legitimate sources. Information has also been extracted from a variety of journal papers. Findings/Result: Even today, managing patients with mental diseases can be challenging, especially when it is felt that they lack the capacity to make intelligent decisions. Due to all of these factors, the practice of psycho-surgery should adopt an integrated method for assessment and therapy. The way psychological therapies are provided in the future will undoubtedly be impacted by concurrent breakthroughs in the fields of behavioral neuroscience, brain imaging, psychological medications, and neurosurgical procedures. According to studies, ablative neurosurgery and “deep brain stimulation” are successful experimental therapies for people with chronic, acute, and “treatment-resistant obsessive-compulsive disorder”, “major depressive disorder”, and “Tourette syndrome”. The careful identification of competent applicants has been guided by suggested criteria. After presenting the details and the expected outcome of the procedure, it is imperative to obtain the person's consent. Originality and Value: In order for readers from all academic disciplines to understand the basic concepts behind psychosurgery and how it can be used to treat a variety of psychological issues, all of the clinical material has been extracted from reliable, scientific publications and organized effectively in this paper without the use of many medical expressions. The scientific complexity of any theoretical or clinical information was avoided, and the material was organized so as to preserve consistency and systematization. Paper Type: Clinical/Healthcare management

Chronic Deep Brain Stimulation of the Human Nucleus Accumbens Region Disrupts the Stability of Intertemporal Preferences.

When choosing between rewards that differ in temporal proximity (intertemporal choice), human preferences are typically stable, constituting a clinically relevant transdiagnostic trait. Here we show, in female and male human patients undergoing deep brain stimulation (DBS) of the anterior limb of the internal capsule/NAcc region for treatment-resistant obsessive-compulsive disorder, that long-term chronic (but not phasic) DBS disrupts intertemporal preferences. Hierarchical Bayesian modeling accounting for temporal discounting behavior across multiple time points allowed us to assess both short-term and long-term reliability of intertemporal choice. In controls, temporal discounting was highly reliable, both long-term (6 months) and short-term (1 week). In contrast, in patients undergoing DBS, short-term reliability was high, but long-term reliability (6 months) was severely disrupted. Control analyses confirmed that this effect was not because of range restriction, the presence of obsessive-compulsive disorder symptoms or group differences in choice stochasticity. Model-agnostic between- and within-subject analyses confirmed this effect. These findings provide initial evidence for long-term modulation of cognitive function via DBS and highlight a potential contribution of the human NAcc region to intertemporal preference stability over time.SIGNIFICANCE STATEMENT Choosing between rewards that differ in temporal proximity is in part a stable trait with relevance for many mental disorders, and depends on prefrontal regions and regions of the dopamine system. Here we show that chronic deep brain stimulation of the human anterior limb of the internal capsule/NAcc region for treatment-resistant obsessive-compulsive disorder disrupts the stability of intertemporal preferences. These findings show that chronic stimulation of one of the brain's central motivational hubs can disrupt preferences thought to depend on this circuit.

Clinician perspectives on levels of evidence and oversight for deep brain stimulation for treatment-resistant childhood OCD

Approximately 10–20% of children with obsessive-compulsive disorder (OCD) have treatment-resistant presentations, and there is likely interest in developing interventions for this patient group, which may include deep brain stimulation (DBS). The World Society for Stereotactic and Functional Neurosurgery has argued that at least two successful randomized controlled trials should be available before DBS treatment for a psychiatric disorder is considered “established.” The FDA approved DBS for adults with treatment-resistant OCD under a humanitarian device exemption (HDE) in 2009, which requires that a device be used to manage or treat a condition impacting 8000 or fewer patients annually in the United States. DBS is currently offered to children ages 7 and older with treatment-resistant dystonia under an HDE. Ethical and empirical work are needed to evaluate whether and under what conditions it might be appropriate to offer DBS for treatment-resistant childhood OCD. To address this gap, we report qualitative data from semi-structured interviews with 25 clinicians with expertise in this area. First, we report clinician perspectives on acceptable levels of evidence to offer DBS in this patient population. Second, we describe their perspectives on institutional policies or protocols that might be needed to effectively provide care for this patient population.

EPD1504: a novel μ-opioid receptor partial agonist attenuates obsessive-compulsive disorder (OCD)-like behaviors.

Low doses of μ-opioid receptor (MOR) agonists rapidly ameliorate symptoms in treatment-resistant obsessive-compulsive disorder (OCD) patients (10-50% of OCD patients). However, the utility of MOR agonists is limited by their safety liabilities. We developed a novel MOR partial agonist (EPD1540) that has an improved respiratory safety profile when compared to buprenorphine. Buprenorphine is a MOR partial agonist primarily used in the treatment of opiate-use disorder, which in investigator-led trials, has been shown to rapidly ameliorate symptoms in treatment-resistant OCD patients. In this study, we show that doses of EPD1504 and buprenorphine that occupy small fractions of MORs in the CNS (approximately 20%) are as effective as fluoxetine at ameliorating OCD-like behaviors in two different rat models (an operant probabilistic reversal task and marble burying). Importantly, effective doses of EPD1504 did not impair either locomotor activity, or respiration under normoxic or hypercapnic conditions. Additionally, EPD1504 had effects comparable to buprenorphine in the conditioned place preference assay. These results indicate that EPD1504 may provide a safer alternative to buprenorphine for the treatment of OCD patients.

Deep brain stimulation for autism spectrum disorder.

Deep brain stimulation (DBS) is a medical treatment that aims to obtain therapeutic effects by applying chronic electrical impulses in specific brain structures and neurological circuits. Over the years, DBS has been studied for the treatment of many psychiatric disorders. Scientific research on the use of DBS in people with autism has focused this interest mainly on treatment-resistant obsessive-compulsive disorder, drug-resistant epilepsy, self-injurious behaviors (SIB), and aggressive behaviors toward the self. Autism spectrum disorder (ASD) includes a group of developmental disabilities characterized by patterns of delay and deviance in the development of social, communicative, and cognitive skills and the presence of repetitive and stereotyped behaviors as well as restricted interests. People with autism often have numerous medical and psychiatric comorbidities that worsen the quality of life of patients and their caregivers. Obsessive-compulsive symptoms can be found in up to 81.3% of people with autism. They are often severe, refractory to treatment, and particularly difficult to treat. SIB has a high prevalence in severely retarded individuals and is often associated with autism. Drug treatment of both autism and SIB presents a therapeutic challenge. To describe the current state of the art regarding the efficacy of DBS in people with ASD, a literature search was conducted for relevant studies using the PubMed database. Thirteen studies have been considered in this paper. Up to date, DBS has been used for the stimulation of the nucleus accumbens, globus pallidus internus, anterior limb of the internal capsule, ventral anterior limb of the internal capsule, basolateral amygdala, ventral capsule and ventral striatum, medial forebrain bundle, and posterior hypothalamus. In the total sample of 16 patients, 4 were adolescents, and 12 were adults. All patients had symptoms resistant to multiple drug therapy. Many patients taken into consideration by the studies showed clinical improvements as evidenced by the scores of the psychopathological scales used. In some cases, clinical improvements have varied over time, which may require further investigation. Among the new therapeutic perspectives, DBS could be a valid option. However, further, and more in-depth research is needed in this field.

Treating Obsessive-Compulsive Disorder by Invasively Modulating Thoughts, Feelings, or Both

The defining characteristic of pathological compulsions is that they are carried out to reduce momentary distress, even though performing the compulsive act or thought is rationally not in the individual’s true best interest. This inability to flexibly adapt is a prominent component of obsessive-compulsive disorder (OCD) and closely related illnesses such as Tourette syndrome and is also observed in substance use disorders ( 1 Figee M. Pattij T. Willuhn I. Luigjes J. van den Brink W. Goudriaan A. et al. Compulsivity in obsessive-compulsive disorder and addictions. Eur Neuropsychopharmacol. 2016; 26: 856-868 Crossref PubMed Scopus (111) Google Scholar ). Following the 20th century experience with ablative procedures such as capsulotomy, deep brain stimulation (DBS) was applied to the treatment of OCD. Electrodes are most commonly placed within the anterior limb of the internal capsule (ALIC), modulating cortico-basal ganglia-thalamo-cortical parallel white matter loops relevant to limbic, associative, and motor functions, respectively. ALIC stimulation has proven to be a highly effective treatment for severe OCD ( 2 Smith AH, Mayberg HS, Figee M (in press): Neuromodulation and psychiatric disorders. In: Nestler EJ, Charney DS, editors. Neurobiology of Mental Illness, 6th ed. New York: Oxford University Press. Google Scholar ). DBS to a different anatomical location, the subthalamic nucleus (STN), was initially developed for Parkinson’s disease, but positive early experience in patients with comorbid Parkinson’s disease and OCD led to research establishing high-frequency stimulation straight to the STN as clinically efficacious for OCD ( 3 Mallet L. Polosan M. Jaafari N. Baup N. Welter M.L. Fontaine D. et al. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med. 2008; 359: 2121-2134 Crossref PubMed Scopus (687) Google Scholar ). In a similar manner, promising early pilot studies led to further exploration of other targets. These include the bed nucleus of the stria terminalis, the “extended amygdala” located between the ALIC and STN targets ( 4 Mosley P.E. Windels F. Morris J. Coyne T. Marsh R. Giorni A. et al. 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. Transl Psychiatry. 2021; 11: 190 Crossref PubMed Scopus (38) Google Scholar ). More recently, evidence has emerged for the effectiveness of stimulation delivered deeper in the midbrain than the STN, adjacent to the ventral tegmental area (VTA)—a source of dopaminergic projections to the cortex (via the medial forebrain bundle [MFB]) and a recipient of proposed regulatory projections back from the cortex (via the “supralateral MFB”) ( 5 Meyer D.M. Spanier S. Kilian H.M. Reisert M. Urbach H. Sajonz B.E. et al. Efficacy of superolateral medial forebrain bundle deep brain stimulation in obsessive-compulsive disorder. Brain Stimul. 2022; 15: 582-585 Abstract Full Text Full Text PDF Scopus (3) Google Scholar ). SEE CORRESPONDING ARTICLE ON PAGE 1010 SEE CORRESPONDING ARTICLE ON PAGE 1010 The Rostral Zona Incerta: A Subcortical Integrative Hub and Potential Deep Brain Stimulation Target for Obsessive-Compulsive DisorderBiological PsychiatryVol. 93Issue 11PreviewThe zona incerta (ZI) is involved in mediating survival behaviors and is connected to a wide range of cortical and subcortical structures, including key basal ganglia nuclei. Based on these connections and their links to behavioral modulation, we propose that the ZI is a connectional hub for mediating between top-down and bottom-up control and a possible target for deep brain stimulation for obsessive-compulsive disorder. Full-Text PDF

Cost-Effectiveness Analysis of Deep Brain Stimulation vs. Treatment as Usual for Treatment-Resistant Obsessive-Compulsive Disorder

Cost-Effectiveness Analysis of Deep Brain Stimulation vs. Treatment as Usual for Treatment-Resistant Obsessive-Compulsive Disorder

155 Cost-Effectiveness Analysis of Deep Brain Stimulation Versus Treatment as Usual for Treatment-Resistant Obsessive-Compulsive Disorder

INTRODUCTION: Deep brain stimulation (DBS) is an effective neurosurgical option for patients with treatment-resistant obsessive-compulsive disorder (TROCD). Despite being more costly than neuroablative procedures of comparable efficacy, DBS has gained popularity for its reversibility. Though its cost-effectiveness has been investigated in movement disorders, few economic analyses of DBS for psychiatric disorders exist. METHODS: We developed decision analytic models to compare the cost-effectiveness of DBS to treatment as usual (TAU) for TROCD, varying device type (non-rechargeable or rechargeable) or time-horizon (three or five years). Effectiveness data were based on literature review. Published algorithms were used to convert Y-BOCS scores into utilities. Costs were approached from the healthcare sector perspective and drawn from Medicare reimbursement rates. Monte Carlo (MC) simulations and probabilistic sensitivity analyses were performed to estimate the incremental cost-effectiveness ratio (ICER) in USD ($) per quality-adjusted life-year (QALY). RESULTS: We included 238 and 265 TROCD patients across 28 studies who underwent DBS and had sufficient follow-up in our 3- and 5-year models, respectively. Non-rechargeable DBS was less cost-effective than TAU (3-year ICER = $153,221/QALY; 5-year ICER = $194,043/QALY). Rechargeable DBS was moderately more cost-effective at three years (ICER = $70,646/QALY) and definitively more cost-effective at five years (ICER = $37,652/QALY) compared to TAU. At three and five years, net QALYs gained were greater in DBS than TAU by 0.36 and 0.59, respectively. At willingness-to-pay thresholds of $50,000/QALY for definitive cost-effectiveness and $100,000/QALY for moderate cost-effectiveness, rechargeable DBS was moderately more cost-effective than TAU at 3 years in 100% and more cost-effective at 5 years in 96% of iterations. CONCLUSIONS: Compared to TAU, in the U.S., rechargeable DBS for TROCD is more cost-effective under a range of possible cost and effectiveness values. However, non-rechargeable DBS is not more cost-effective than TAU for TROCD due to high costs of battery replacement.

An update on the Pharmacological and Psychotherapeutic Management of Treatment Resistant OCD

AbstractAlthough the rates of response to first-line pharmacological treatments (serotonin reuptake inhibitors – SRIs) are generally twice that of placebo, only 40-60% of patients respond sufficiently or are able to tolerate traditional first-line pharmacotherapy. Augmentation with dopamine antagonist medications is associated with the strongest evidence, yet dopamine antagonists benefit only a minority of those who try them and carry elevated risks of adverse effects. Based on evolving pathophysiologic models of OCD, a variety of agents targeting serotonin, dopamine, norepinephrine, glutamate, and anti-inflammatory pathways have been explored as alternative or adjunctive therapies for treatment-resistant OCD and have at least preliminary evidence of efficacy. Similarly, approximately 50% of patients do not respond optimally to first psychotherapeutic treatments including cognitive behavioural therapy (CBT) and exposure and response prevention (ERP), even when combined with pharmacotherapy. The psychotherapy outcome literature is heterogeneous and very few psychological strategies have been developed specifically to treat treatment resistant OCD. However, a recent systematic review concluded that CBT improved treatment response in individuals with pharmacotherapy resistance. This presentation will present an update on the pharmacological and psychotherapeutic treatment of refractory OCD including novel strategies such as the use of psychedelics.Disclosure of InterestM. Van Ameringen Grant / Research support from: Elvium, CIHR,Hamilton Academic Health Sciences Organization, Consultant of: Abbvie, Bausch Health, Boehringer Ingelheim, Elvium, Jazz, Vistagen, Speakers bureau of: Abbvie, Elvium (Purdue), Lundbeck, Otsuka, Sunovion, and Takeda

Electroencephalographic study of the Error Related Negativity in patients suffering from treatment-resistant obsessive-compulsive disorder

IntroductionThe physiopathology of patients with treatment-resistant obsessive-compulsive disorder (OCD) may differ from that of treatment-responsive patients. Cognitive evoked potentials may be one of the ways to detect these differences. The error-related negativity (ERN) is an electrophysiological correlate of error detection during the execution of a motor task, which is larger in patients with OCD than in typical people. According to the literature, the ERN could vary according the patients’ treatment-resistance.ObjectivesThe main goal of this study was to assess whether the ERN, which begins 20 ms before the motor response and reaches its maximum 80 ms later, was different between non-resistant and highly resistant OCD patients.MethodsForty-seven OCD patients and their age- and gender-matched controls were asked to perform a flanker task while the potentials evoked by their motor responses were recorded. For each participant, the difficulty of the task was adjusted to get an error rate of about 20%. Treatment-resistance was evaluated using Pallanti and Quercioli’s (Prog Neuropsychopharmacol Biol Psychiatry 2006; 30 400-412) resistance scales.ResultsIn all participants, response errors evoked an ERN at fronto-central electrodes [Fz, FCz, red and green lines on the figure], whereas the negativity was absent or smaller for correct responses (black and blue lines on the figure, both ps < .01). As expected, the ERN of OCD patients was consistently larger and of longer duration than that of control participants (compare the green and blue lines with the red and black ones, respectively). Interestingly, the amplitude of the potentials evoked by correct responses at central and centro-parietal electrodes on the left side of the brain [C5, C3, CP5] was significantly less negative in treatment-resistant patients (all ps < .05). In control participants, the ERN recorded at fronto-central electrodes were followed by a positive wave which reached its maximum between 170 and 270 ms after the response, and was larger after errors than after correct response. In OCD patients in contrast, this positive wave was absent whether the response was correct or not.Image:ConclusionsThe significant correlation observed between OCD patients’ treatment resistance and the potential evoked by correct responses on the left side of the brain suggest that this potential could be used as a marker of treatment-resistance. The absence in OCD patients of the positive wave that follows the ERN in control participants suggests that OCD patients were not fully aware of whether or not their response was correct.Disclosure of InterestNone Declared

Rituximab for treatment-resistant schizophrenia and/or obsessive-compulsive disorder (OCD): functional connectivity and cytokines associated with symptomatic improvements

IntroductionImmunological mechanisms may contribute to the causation of mental illness. Autoimmunity is most convincingly shown for anti-NMDA-R encephalitis and Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS); disorders that overlap clinically with schizophrenia and OCD. Altered inflammatory cytokine production, glial activation and auto-antibodies have also been associated with schizophrenia and OCD. In these disorders, however, the treatment results with anti-inflammatory or immunomodulating drugs have hitherto been limited and inconsistent. Yet other targets within the immune system may still be effective and new options are warranted for treatment-resistant patients. Rituximab targets B-lymphocytes and is often used in autoimmune disorders such as rheumatoid arthritis, multiple sclerosis and anti-NMDA-R encephalitis.ObjectivesWe aimed to investigate whether rituximab is clinically effective, safe and tolerable as add-on therapy in markedly ill, treatment-resistant adult psychiatric patients with schizophrenia or OCD. We also wanted to identify putative mediating mechanisms in treatment responders, such as cytokine changes and functional connectivity (FC).MethodsIn an open pilot study, adults (18-39 years) with treatment-resistant schizophrenia and/or OCD were included. They received an intravenous infusion of rituximab 1000 mg, once at baseline, in addition to their regular psychiatric medication and were followed for 1 year. The main outcome measures were the Positive and Negative Syndrome Scale (PANSS) or Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Clinical Global Impression-Improvement scale (CGI-I) and the Personal and Social Performance scale (PSP). Treatment response was defined as ≥ 40 % decrease in PANSS or ≥ 35 % decrease in Y-BOCS, and much improved according to CGI-I. Resting-state fMRI was applied at baseline and after 5 months. Plasma cytokines were measured at 0, 3 and 5 months. Cognitive tests and the recently developed PsychoNeuroinflammatory Related Signs and Symptoms Inventory (PNISSI) were used to identify and measure symptoms related to neuro-inflammation and cognitive function.ResultsNineteen patients were treated with rituximab. 3-5 months after treatment, 6/9 patients with schizophrenia and 1/10 with OCD responded. One schizophrenia patient continues with rituximab every 6 months and has reportedly done well for almost 3 years. No severe side effects were reported apart from recurrent abdominal pain in a schizophrenia patient and one case of post-COVID-19 syndrome. Significant changes of FC were detected in responders only and correlated with PSP changes.ConclusionsAberrant B-cell activities may contribute to treatment-resistant schizophrenia and be amenable to treatment with rituximab. However, the results of this pilot study need confirmation in placebo-controlled trials.Disclosure of InterestNone Declared

FMRI neurofeedback leads to long-term symptomatic reduction in treatment-resistant patients with obsessive-compulsive disorder

Introduction Obsessive‐compulsive disorder (OCD) is a severe condition with a profound impact on the health, social and professional functioning of the patients. More than one third of the patients do not achieve remission of the symptoms after first‐line treatment with cognitive‐behavioral therapy and selective serotonin reuptake inhibitor medication. Neurofeedback is a promising technique that allows the non‐invasive self‐regulation of neural activity associated with symptomatic manifestation. Previous literature reported preliminary evidence of positive effects of functional magnetic resonance imaging (fMRI) neurofeedback on OCD symptoms. However, these studies have small samples and/or were not controlled. Additionally, these studies did not involve treatment‐resistant patients. Objectives We aim at developing a fMRI neurofeedback task to treatment-resistant OCD patients and to explore the underlying brain changes. Methods We implemented a sham‐controlled double‐blinded fMRI neurofeedback protocol to target hyperactivity in orbitofrontal regions in treatment‐resistant OCD patients with contamination/cleaning symptoms. The protocol had two sessions of neurofeedback (72 min of total training). The patients included were under treatment‐as‐usual. Results Our preliminary results with the experimental group (n = 10 patients) demonstrated decreased OCD and stress symptoms three months after the neurofeedback sessions. Moreover, immediately after the neurofeedback sessions, we observed reduced functional connectivity between orbitofrontal and temporoparietal regions, and increased brain activity in dorsolateral prefrontal and premotor areas during symptomatic provocation. The brain functional changes might be associated with a better control over obsessions. Conclusions fMRI neurofeedback led to long-term symptomatic reduction in treatment-resistant patients with OCD. Our results need further validation with the sham‐control group but highlight the efficacy of fMRI neurofeedback for refractory OCD and the necessity of prolonged neurofeedback protocols. Disclosure of Interest None Declared