Treatment-resistant Obsessive-compulsive Disorder Patients Research Articles

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.

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.

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.

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.

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.

Cost-effectiveness analysis of radiosurgical capsulotomy versus treatment as usual for treatment-resistant obsessive-compulsive disorder.

Stereotactic radiosurgical capsulotomy (SRS-C) is an effective neurosurgical option for patients with treatment-resistant obsessive-compulsive disorder (TROCD). Unlike other procedures such as deep brain stimulation and radiofrequency ablation, the cost-effectiveness of SRS-C for TROCD has not been investigated. The authors herein report the first cost-effectiveness analysis of SRS-C for TROCD. Using a decision analytic model, the authors compared the cost-effectiveness of SRS-C to treatment as usual (TAU) for TROCD. Treatment response and complication rates were derived from a review of relevant clinical trials. Published algorithms were used to convert Yale-Brown Obsessive Compulsive Scale scores into utility scores reflecting improvements in quality of life. Costs were approached from the healthcare sector perspective and were drawn from Medicare reimbursement rates and available healthcare economics data. A Monte Carlo simulation and probabilistic sensitivity analysis were performed to estimate the incremental cost-effectiveness ratio. One hundred fifty-eight TROCD patients across 9 studies who had undergone SRS-C and had at least 36 months of follow-up were included in the model. Compared to TAU, SRS-C was more cost-effective, with an estimated incremental cost-effectiveness ratio of $28,960 per quality-adjusted life year (QALY) gained. Within the 3-year time horizon, net QALYs gained were greater in the SRS-C group than the TAU group by 0.27 (95% CI 0.2698-0.2702, p < 0.0001). At willingness-to-pay thresholds of $50,000 and $100,000 per QALY, the Monte Carlo simulation revealed that SRS-C was more cost-effective than TAU in 83% and 100% of iterations, respectively. Compared to TAU, SRS-C for TROCD is more cost-effective under a range of possible cost and effectiveness values.

Repetitive Transcranial Magnetic Stimulation in a Group of Treament-Resistant Obsessive-Compulsive Disorder Patients: A Descriptive Study

Objective: This study aims to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) treatment in a group of treatment-resistant obsessive-compulsive disorder (OCD) patients and to examine the relationship between various sociodemographic and clinical variables and treatment response. Materials and Methods: Data including The Yale–Brown Obsessive Compulsive Scale (Y-BOCS) scores and various clinical and sociodemographic characteristics of 27 treatment-resistant OCD patients who received 30 sessions of low-frequency rTMS (LF-rTMS) treatment on the left dorsolateral prefrontal cortex (DLPFC) were analyzed. Results: Mean Y-BOCS scores decreased significantly across week 0 and the 3rd week (t(26)=10.59, p&lt;.001) and continued to decrease significantly across weeks 3 and 6 (t(26)=11.47, p&lt;.001). 21(78%) patients were responders with at least a %25 decrease in the mean Y-BOCS scores, and 10(47.6%) of these 21 patients also met the complete response criteria with a 35% or more reduction in Y-BOCS. No significant difference was observed between responders and non-responders regarding various clinical and sociodemographic variables. The only reported side effects were headaches and local scalp tenderness, which improved in a short time. Conclusion: This descriptive study has demonstrated the efficacy of a long-duration LF-rTMS application on the DLPFC in a group of drug-resistant OCD patients. This finding might contribute to the available literature, especially in drawing out a standardized treatment protocol in these cases.

Deep brain stimulation in the bed nucleus of the stria terminalis: A symptom provocation study in patients with obsessive-compulsive disorder

Deep brain stimulation (DBS) is an emerging therapy for treatment-resistant obsessive-compulsive disorder (OCD), and several targets for electrode implantation and contact selection have been proposed, including the bed nucleus of the stria terminalis (BST). Selecting the active electrode contacts (patients typically have four to choose from in each hemisphere), and thus the main locus of stimulation, can be a taxing process. Here, we investigated whether contact selection based purely on their neuroanatomical position in the BST is a worthwhile approach. For the first time, we also compared the effects of uni- versus bilateral BST stimulation. Nine OCD patients currently receiving DBS participated in a double-blind, randomized symptom provocation study to compare no versus BST stimulation. Primary outcomes were anxiety and mood ratings in response to disorder-relevant trigger images, as well as ratings of obsessions, compulsions, tendency to avoid and overall wellbeing. Furthermore, we asked whether patients preferred the electrode contacts in the BST over their regular stimulation contacts as a new treatment setting after the end of the task. We found no statistically significant group differences between the four conditions (no, left, right and bilateral BST stimulation). Exploratory analyses, as well as follow-up data, did indicate that (bilateral) bipolar stimulation in the BST was beneficial for some patients, particularly for those who had achieved unsatisfactory effects through the typical contact selection procedure. Despite its limitations, this study suggests that selection of stimulation contacts in the BST is a viable option for DBS in treatment-resistant OCD patients.

Compassion-Focused Group Therapy for Treatment-Resistant OCD: Initial Evaluation Using a Multiple Baseline Design.

Obsessive–compulsive disorder (OCD) is a debilitating mental health disorder that can easily become a treatment-resistant condition. Although effective therapies exist, only about half of the patients seem to benefit from them when we consider treatment refusal, dropout rates, and residual symptoms. Thus, providing effective augmentation to standard therapies could improve existing treatments. Group compassion-focused interventions have shown promise for reducing depression, anxiety, and avoidance related to various clinical problems, but this approach has never been evaluated for OCD individuals. However, cultivating compassion for self and others seems crucial for OCD patients, given the accumulating research suggesting that fear of guilt, along with isolation and self-criticism, can strongly contribute to the development and maintenance of OCD. The primary aim of this pilot study was to evaluate the acceptability, tolerability, and effectiveness of an 8-week group compassion-focused intervention for reducing OCD symptoms, depression, fear of guilt and self-criticism, and increasing common humanity and compassionate self-reassuring skills in treatment-resistant OCD patients. Using a multiple baseline experimental design, the intervention was evaluated in a sample of OCD patients (N = 8) who had completed at least 6 months of CBT treatment for OCD, but who continued to suffer from significant symptoms. Participants were randomized to different baseline assessment lengths; they then received 8 weekly, 120-min group sessions of compassion-focused therapy for OCD (CFT-OCD), and then were tested again at post-treatment and at 1 month follow up. Despite the adverse external circumstances (post-treatment and follow-up data collection were carried out, respectively, at the beginning and in the middle of the Italian lockdown due to the COVID-19 pandemic), by the end of treatment, all participants demonstrated reliable decreases in OCD symptoms, and these improvements were maintained at 4-week follow-up for seven of eight participants. The intervention was also associated with improvements in fear of guilt, self-criticism, and self-reassurance, but less consistent improvements in depression and common humanity. Participants reported high levels of acceptability of and satisfaction with the intervention. Results suggest that the intervention may be beneficial as either a stand-alone treatment or as an augmentation to other treatments.

Investigational and Experimental Drugs to Treat Obsessive-Compulsive Disorder.

Treatment-resistance is a frequent condition for obsessive-compulsive disorder (OCD). Over the past decades, a lot of effort has been made to address this issue, and several augmentation strategies of serotonergic drugs have been investigated. Antidopaminergic drugs are considered the first choice as augmentation strategy for treatment-resistant OCD patients, but they seem to work only for a subset of patients, and none of them have been officially approved for OCD. Recently, the role of glutamate and inflammation in OCD pathophysiology clearly emerged, and this has led to several investigations on glutamatergic and anti-inflammatory agents. Results seem promising but still inconclusive. Probiotic interventions (considered to modulate the immune systems and the brain activity) are gaining attention in several psychiatric fields but are still at their early stages in the OCD field. Research on new treatment approaches for OCD is moving forward, and more than one hundred interventional trials are ongoing around the world. While the vast majority of these trials involve neuromodulation and psychotherapeutic approaches, only a small proportion (around 20%) involve the investigation of new pharmacological approaches (tolcapone, nabilone, psilocybin, troriluzole, nitrous oxide, rituximab, naproxen, and immunoglobulins). Here, we provide a comprehensive review of investigational and experimental drugs to treat OCD.

Disrupted pathways from the frontal-parietal cortices to basal nuclei and the cerebellum are a feature of the obsessive-compulsive disorder spectrum and can be used to aid in early differential diagnosis

A marker for distinguishing patients with obsessive-compulsive disorder (OCD) spectrum has not yet been identified. Whole-brain resting-state effective and functional connectivity (rsEC and rsFC, respectively) networks were constructed for 50 unmedicated OCD (U-OCD) patients, 45 OCD patients in clinical remission (COCD), 47 treatment-resistant OCD (T-OCD) patients, 42 chronic schizophrenia patients who exhibit OCD symptoms (SCHOCD), and 50 healthy controls (HCs). Multivariate pattern analysis (MVPA) was performed to investigate the accuracy of using connectivity alterations to distinguished among the aforementioned groups. Compared to HCs, rsEC connections were significantly disrupted in the U-OCD (n = 15), COCD (n = 8), and T-OCD (n = 19) groups. Additionally, 21 rsEC connections were significantly disrupted in the T-OCD group compared to the SCHOCD group. The disrupted rsEC networks were associated mainly with the frontal-parietal cortex, basal ganglia, limbic regions, and the cerebellum. Classification accuracies for distinguishing OCD patients from HCs and SCHOCD patients ranged from 66.6% to 98.0%. In conclusion, disrupted communication from the frontal-parietal cortices to subcortical basal nuclei and the cerebellum may represent a functional pathological feature of the OCD spectrum. MVPA based on both abnormal rsEC and rsFC patterns may aid in early differential diagnosis of OCD.

Is twice daily LF-rTMS a viable treatment option for treatment-resistant OCD? Results from an open-label feasibility study.

Several reports point to the beneficial effects of repetitive transcranial magnetic stimulation (rTMS) in the treatment of resistant obsessive-compulsive disorder (OCD). This study aimed to evaluate the safety and efficacy of rTMS targeting the dmPFC in the treatment of treatment-resistant OCD patients. Twelve patients received 20 sessions of low-frequency (LF) rTMS (1Hz, 1200 pulses) in a twice daily protocol during 10weekdays. Y-BOCS and IDS scores modestly but significantly decreased after treatment and at follow-up and HADS anxiety improved at follow-up. LF rTMS may improve OCD, anxiety, and depressive symptoms in treatment-resistant OCD and was a safe and well-tolerated treatment.

Prediction of treatment resistance in obsessive compulsive disorder patients based on EEG complexity as a biomarker

ObjectiveThis study aimed to identify an Electroencephalography (EEG) complexity biomarker that could predict treatment resistance in Obsessive compulsive disorder (OCD) patients. Additionally, the statistical differences between EEG complexity values in treatment-resistant and treatment-responsive patients were determined. Moreover, the existence of correlations between EEG complexity and Yale-Brown Obsessive Compulsive Scale (YBOCS) score were evaluated. MethodsEEG data for 29 treatment-resistant and 28 treatment-responsive OCD patients were retrospectively evaluated. Approximate entropy (ApEn) method was used to extract the EEG complexity from both whole EEG data and filtered EEG data, according to 4 common frequency bands, namely delta, theta, alpha, and beta. The random forests method was used to classify ApEn complexity. ResultsApEn complexity extracted from beta band EEG segments discriminated treatment-responsive and treatment-resistant OCD patients with an accuracy of 89.66% (sensitivity: 89.44%; specificity: 90.64%). Beta band EEG complexity was lower in the treatment-resistant patients and the severity of OCD, as measured by YBOCS score, was inversely correlated with complexity values. ConclusionsThe results indicate that, EEG complexity could be considered a biomarker for predicting treatment response in OCD patients. SignificanceThe prediction of treatment response in OCD patients might help clinicians devise and administer individualized treatment plans.

Randomized sham-controlled trial of continuous theta-burst transcranial magnetic stimulation (cTBS) in the treatment–resistant obsessive–compulsive disorder

Background Obsessive-compulsive disorder (OCD) is a complex disorder with 40 to 60% of patients refractory to treatment. Developing alternatives to classical therapies would be helpful, and neuromodulation techniques offer promising perspectives. Theta-burst transcranial magnetic stimulation (TBS) has been shown to induce potent and long lasting effects on cortical excitability. Cortical inhibition of supplementary motor area (SMA) with low-frequency repetitive transcranial magnetic stimulation (rTMS) showed clinical benefits in OCD. The aim of the present study is to evaluate therapeutic efficacy and tolerability of continuous TBS (cTBS) over the SMA in treatment-resistant OCD patients using a double blind, sham-controlled design. Methods Thirty treatment resistant OCD outpatients (15 women and 15 men) were randomized to receive either active cTBS or sham cTBS for 6 weeks (5 sessions per week). Each treatment session consisted of 1800 stimuli at an intensity of 70% of resting motor threshold. Patients were evaluated at baseline, end of treatment (week 6), and follow-up (week 12). Response to treatment was defined as at least 25% decrease on the Yale–Brown Obsessive Compulsive Scale (YBOCS). Results Treatment was well tolerated. However, there was no significant difference decrease in Y-BOCS scores, at baseline, weeks 6 and 12, between active and sham cTBS group. Responder rates were not different between groups at week 6 (cTBS 21% versus sham 36%; P = 0.678) and week 12 (cTBS 29% versus sham 36%; P = 1). Depressive and anxious symptoms improvement was also similar in the two groups. Conclusion This study is the first controlled trial using cTBS in OCD treatment refractory patients. Our results suggest that the use of cTBS over the SMA is safe but not sufficient to improve OCD symptoms. Further studies are needed to understand why cTBS is less efficient in reducing OCD symptoms compared to rTMS.

Comparative efficacy and tolerability of antipsychotics as augmentations in adults with treatment-resistant obsessive-compulsive disorder: A network meta-analysis

We performed a network meta-analysis to build clear hierarchies of efficacy and tolerability of antipsychotics to augment serotonin reuptake inhibitors (SRIs) for treatment-resistant obsessive-compulsive disorder (OCD) in adults. PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched on September 8, 2018. Randomized controlled trials investigating antipsychotics as augmentation agents were included. Network meta-analyses were performed using frequentist methods. Efficacy was measured by the Yale-Brown Obsessive-Compulsive Scale. Tolerability was measured by side-effect discontinuations. Mean differences (MDs) and odds ratios (ORs) were reported with 95% confidence intervals (CIs). Twenty articles with 790 patients were included. Our analyses showed that there was no significant difference in efficacy between antipsychotic agents. The order of efficacy rankings was inconsistent between primary analysis and sensitivity analyses. We found that there was considerable heterogeneity between studies. Comorbid tics was identified as a significant moderator. All antipsychotics except paliperidone were significantly superior to placebo in the subgroup without comorbid tics, while no antipsychotics was significantly superior to placebo in the comorbid tics subgroup. With respect to tolerability, quetiapine (OR, 3.45; 95% CI, 1.04–11.11) and paliperidone (20.00; 1.01->100) were significantly less tolerable than placebo. Based on this network meta-analysis, antipsychotic agents as augmentations to SRIs might be more effective in treatment-resistant OCD patients without comorbid tics. Definitive determination of which drug is optimal cannot be drawn currently because of the limited numbers of studies and heterogeneity across studies.

Pharmacotherapy for treatment-respondent vs. refractory obsessive–compulsive disorder in children and adults: strategies, meta-analyses and clinical guidelines

Obsessive–compulsive disorder (OCD) is a common mental and anxiety disorders occurs at all ages, but more common in younger ages with uncontrollable, and affects 1–1.5% of the general population. Many pharmacological therapies and drugs have been reported to diminish OCD symptoms, as well as increase quality of life. So far, several meta-analyses, however, have directly compared such treatment approaches in OCD and treatment-resistant OCD patients. This review evaluated all treatment options for OCD in both children and adolescents, and aimed to found if existing pharmacological therapies work similarly well, taking into account medical comorbidities such as substance use, anxiety, metabolic disorders, and finally, an overview of issues related to safety and monitoring. Our review included data from 16 meta-analyses and 8 practical guidelines involving OCD patients. In adults with OCD, we found that combined therapy shows favorable outcome versus SRI alone and produced better results. In children with OCD greatest incremental treatment gains occur early in SSRI treatment. Finally in treatment-resistant OCD patients antipsychotic augmentation of SRIs can be regarded as an evidence-based measure for pharmacological therapy. The results of this review mostly support the formerly published reviews on the pharmacological management of OCD. Albeit we could confirm that combination/augmentation of SSRIs significantly improved symptoms in treatment-resistant OCD patient than monotherapy. From a clinical perspective, antipsychotics combination/augmentation of SSRIs should be favorably used if there are comorbidities psychosis that represents a frequent comorbidity in OCD, especially the presence of comorbidities is highly associated with treatment-resistance OCD condition.

N-Acetyl Cysteine and Vitamin D Supplementation in Treatment Resistant Obsessive-compulsive Disorder Patients: A General Review.

Obsessive-compulsive Disorder (OCD) is a disabling mental illness for which pharmacological and psychosocial interventions are all too often inadequate. This demonstrates the need for more targeted therapeutics. Recent preclinical and clinical studies have implicated the dysfunction of glutamatergic neurotransmission in the pathophysiology of OCD. Moreover, there are studies suggesting that neuroimmune abnormalities may play an important role in the pathogenesis of OCD. N-acetyl cysteine (NAC) is a safe and readily available agent that would modify the synaptic release of glutamate in subcortical brain regions via modulation of the cysteine-glutamate antiporter. The modulation of inflammatory pathways may also play a role in the benefits seen following NAC treatment. Therefore NAC can be considered a neuroprotective agent. This paper explores the role of NAC in the treatment of OCD conditions refractory to first-line pharmacological interventions, reviewing the clinical studies published in the last decade. The possible benefit mechanisms of NAC for this disorder will be discussed, as well as the role of vitamin D supplementation, given its specific property of stimulating the formation of glutathione in the brain. Nutraceutical supplementation in treatment resistance OCD may be important not only for improving obsessive-compulsive symptomatology, but also from a psychological perspective, given its better acceptance by the patients compared to pharmacological treatment.

Repetitive transcranial magnetic stimulation of the supplementary motor area in treatment-resistant obsessive-compulsive disorder: An open–label pilot study

Obsessive-compulsive disorder (OCD) is a severely distressing disorder represented by obsessions and compulsions. A significant proportion of OCD patients fail to improve with conventional treatment methods. Repetitive transcranial magnetic stimulation (rTMS) has been proposed as an alternative for OCD treatment. Functional neuroimaging studies indicate that OCD is associated with increased activity in the supplementary motor area (SMA), a region that plays an important role in the pathophysiology of this disorder. In this study, we assessed the efficacy of augmentation with 1Hz rTMS over the SMA in treatment-resistant OCD patients. The participants received 1Hz rTMS over the SMA in 20 daily sessions for 4weeks. We observed significant reduction in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score at the 4th week of the treatment. Reduction in compulsion contributed to the reduction of global Y-BOCS whereas there was no significant reduction in obsession. Clinical global impression-global improvement also showed significant change at the 2nd and 4th week of the treatment. No additional significant changes or significant adverse effects were seen. These findings suggest that 1Hz rTMS over the SMA can be an efficient and safe add-on therapeutic method in treatment-resistant patients with OCD. Further controlled studies in larger samples are required to confirm the effect of 1Hz rTMS over the SMA in OCD.

PREGABALIN AUGMENTATION IN TREATMENT-RESISTANT OBSESSIVE-COMPULSIVE DISORDER : CASE SERIES

Background Obsessive compulsive disorder (OCD) is a syndrome characterised by obsessions and compulsions, as well as other neuropsychiatric features, and is often associated with primary psychiatric disorders and various neurologic conditions. Despite the beneficial effect of selective serotonin reuptake inhibitors (SSRIs) in OCD, up to 40% of patients remain refractory to treatment. The therapeutic limitations of standard psychopharmacological treatments of OCD warrant the investigation of other treatment strategies. One potential candidate is pregabalin, a novel analogue of the inhibitory neurotransmitter gamma amino butyric acid (GABA). Pregabalin has been shown to be efficacious in other anxiety disorders and in a recent open-label trial was found to lead to a significant improvement in clinical symptoms in treatment-resistant OCD patients . We present findings from a case series of inpatients with severe, complex, and resistant obsessive-compulsive disorder (OCD) whose treatment was augmented with pregabalin. Methods: The National Obsessive Compulsive Disorder/Body Dysmorphic Disorder (OCD/BDD) Service at South West London and St George’s Mental Health NHS Trust, affiliated with St George's University of London, is one of five nationally funded tertiary centres providing outreach across all regions in England. This case series consisted of 16 patients, 11 men and 5 women, with severe OCD, as defined by a score of 30 or more on the Yale-Crown Obsessive Compulsive Scale (YBOCS), who were treated with pregabalin during the course of their admission to the above unit in the time period December 2013-June 2015. We compared YBOCS scores at discharge against the patient’s initial severity and also examined patient notes to gather anonymised qualitative data for case vignettes to further elucidate their treatment experiences. Results The median age of patients was 38.5 years at the time of admission and the median duration of admission was 6 months. The median dosage of pregabalin at the time of discharge was 300mg/day, representing a median dose increase of 150mg/day from admission. Improvement in patients’ OCD symptoms was observed with a median reduction in YBOCS score of 13, reflecting a median 33% reduction in symptom severity. Case vignettes showed that adjunctive pregabalin was generally well-tolerated. Discussion In severe OCD a 30% reduction in symptom severity is seen as a reasonable aim; the improvement seen therefore represents a clinically meaningful change. To the best of our knowledge, so far only one study has been published looking at pregabalin as an adjunctive treatment in treatment-resistant OCD. Our findings were consistent with theirs, and in addition we were able to examine changes in YBOCS scores over a longer duration. There are several important limitations to this case series - namely, its small sample-size, lack of control group, the fact that participants were non-blinded, and that we were not able to control for the therapeutic effects of the hospital environment. However, given the lack of currently available data around the use of pregabalin as an adjunctive agent, this data represents a meaningful step in this burgeoning area of research. We would encourage further research that addresses the aforementioned limitations.

The Efficacy of Aripiprazole versus Risperidone as Augmentation Therapy in the Treatment of the Resistant Obsessive-Compulsive Disorder: A Double-Blind Clinical Trial

Background: Obsessive-compulsive disorder (OCD) is the fourth common psychiatric disorder. Among the anxiety disorders, OCD has the least therapeutic response and 40-60% of OCD patients do not satisfactorily respond to the first-line standard treatment known as treatment-resistant OCD. One of the best therapeutic strategies is the augmentation therapy, which is adding antipsychotics to the standard treatment (SSRIs). Objectives: This study was aimed at comparing the efficacy of Risperidone and Aripiprazole as augmentation therapy in the resistant cases of obsessive-compulsive disorder. Methods: In this double-blind randomized clinical trial, 100 patients with treatment-resistant OCD were diagnosed based on the DSM-IV-TR and were followed for 12-weeks. The patients were randomly divided into two groups of Aripiprazole and Risperidone and received an average daily dose of 5 mg and 1.5 mg for twelve weeks, respectively. The efficacy of treatment was measured and compared by the Yale-brown obsessive-compulsive scale (Y-BOCS) at 4, 8 and 12 weeks. Results: The mean Y-BOCS score of patients in Risperidone and Aripiprazole groups were 25.26 ± 4.17 and 25.02 ± 4.46; respectively and had no significant difference (P = 0.79) at the beginning of the trial. At the end of the study (12th week), it was changed for the Risperidone and Aripiprazole groups to 20.00 ± 4.45 and 16.24 ± 4.41, respectively (P < 0.001). Furthermore, there was a significant decreasing trend of Y-BOCS scores in both groups, which was demonstrated by the repeated measurement analysis (P < 00.1). Conclusions: It was found that both Aripiprazole and Risperidone could be effective in the treatment of treatment-resistant OCD patients. However, Aripiprazole showed a higher efficacy compared to Risperidone.