Treatment-refractory Obsessive-compulsive Disorder Patients Research Articles

Evaluation of changes in neural oscillation after bilateral capsulotomy in treatment refractory obsessive-compulsive disorder using magnetoencephalogram.

Bilateral thermal capsulotomy with magnetic resonance-guided focused ultrasound (MRgFUS-capsulotomy) is a promising treatment option for treatment-refractory obsessive-compulsive disorder (OCD). Herein, we investigated the effects of bilateral thermal capsulotomy with MRgFUS on neural oscillations in treatment-refractory OCD patients. Eight patients underwent resting-state MEG with repeated recordings before and 1 and 6 months after MRgFUS-capsulotomy, and the oscillatory power and phase coherence over the entire cortical sensor area were measured. After MRgFUS-capsulotomy, the high beta band power in the fronto-central and temporal areas decreased at 1 month and remained stable for 6 months. Cortical connectivity of the high beta band gradually decreased over the entire cortical area during the following 6 months. At 1 month, improvement in anxiety and depression symptoms was significantly correlated with changes in high beta band power in both the frontotemporal and temporal areas. The treatment effect of MRgFUS-capsulotomy may be attributed to the cortical high beta band. Our results provide an advanced understanding of the neural mechanisms underlying MRgFUS-capsulotomy and other neuromodulatory interventions for treatment-refractory OCD.

Network analysis in Gamma Knife capsulotomy for intractable obsessive-compulsive disorder

IntroductionGamma-knife Ventral Capsulotomy (GVC) has been suggested as an efficacious treatment for a subset of patients with treatment refractory obsessive compulsive disorder (OCD). Research questionThe goal of this study was to investigate neural correlates of GVC and investigate the predictive value of white matter tracts that are known to be associated with clinical outcome to Deep Brain Stimulation (DBS). Material and methodsMR images of 8 treatment-refractory OCD patients with a minimum follow-up of 3-years who underwent GVC were used to correlate lesion characteristics with symptom improvement. This exploratory study investigated relations between differences in cortical grey matter structure and subcortical structures before and after GVC for responding and non-responding patients (n ​= ​6). Normative diffusion MRI- based tractography was used to determine networks associated with successful lesions. ResultsThe mean total Y-BOCS reduction was 19.6 after three years, resulting in a response rate of 63%.The strongest correlation with symptom improvement was found for a decrease of the left ventral diencephalon volume (r ​= ​−0.83, p ​= ​0.039). Discriminative tractography suggest streamlines connecting the prefrontal cortex with the subthalamic nucleus to be associated with clinical response. However, results could not be validated either implicating interpatient anatomical variability or reflecting the relative small sample size as a limitation. Discussion/ConclusionTaken together, the present study highlights the efficacy of GVC in patients with treatment-refractory OCD. Our results are suggestive of GVC treatment efficacy being mediated by the involvement of a subpart of the ALIC connecting the PFC and the STN.

Cognitive deficits and clinical symptoms in patients with treatment-refractory obsessive–compulsive disorder: The role of slowness in information processing

Patients with Obsessive–Compulsive Disorder (OCD) present neuropsychological deficits across different cognitive domains, especially in executive functioning and information processing speed. Some studies have even suggested that speed deficits may underlie poor neuropsychological performance. However, this hypothesis remains unanswered in both OCD general population and OCD refractory subgroup. In addition, it is not clear whether such deficits are secondary to the clinical symptoms or may constitute a primary deficit. The aim of this study was to explore the speed of processing hypothesis in treatment-refractory OCD patients, and to clarify to what extent slowness is related to psychopathological symptoms. Both clinical and neuropsychological examination was conducted to assess 39 OCD refractory patients candidates for neurosurgery and 39 healthy matched individuals. Principal component analysis revealed a three-component structure in the neuropsychological battery being used, including a speed of processing, working memory, and conflict monitoring components. Group comparisons revealed that OCD patients performed significantly worse than healthy individuals in speed measures, but no differences were found in executive tests not influenced by time. Correlation analyses revealed a lack of association between neuropsychological and clinical measures. The results suggest that treatment-refractory OCD patients exhibit a primary deficit in information processing speed independent of clinical symptoms.

Invasive and Non-invasive Neurostimulation for OCD.

It becomes increasingly clear that (non-)invasive neurostimulation is an effective treatment for obsessive-compulsive disorder (OCD). In this chapter we review the available evidence on techniques and targets, clinical results including a meta-analysis, mechanisms of action, and animal research. We focus on deep brain stimulation (DBS), but also cover non-invasive neurostimulation including transcranial magnetic stimulation (TMS). Data shows that most DBS studies target the ventral capsule/ventral striatum (VC/VS), with an overall 76% response rate in treatment-refractory OCD. Also TMS holds clinical promise. Increased insight in the normalizing effects of neurostimulation on cortico-striatal-thalamic-cortical (CSTC) loops - through neuroimaging and animal research - provides novel opportunities to further optimize treatment strategies. Advancing clinical implementation of neurostimulation techniques is essential to ameliorate the lives of the many treatment-refractory OCD patients.

Electrophysiological and imaging evidence of sustained inhibition in limbic and frontal networks following deep brain stimulation for treatment refractory obsessive compulsive disorder.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that arises from a complex interaction of environmental and genetic factors. Despite numerous pharmacological and behavioral interventions, approximately 10% of patients remain refractory. High-frequency deep brain stimulation (HF-DBS) has shown promising results for treatment-refractory OCD. We report the follow-up result of up to 6 years of 4 treatment-refractory OCD patients treated by HF-DBS. Targets of stimulation were the anterior limb of the internal capsule (ALIC) in two cases, and the nucleus accumbens (NAc) in the remaining cohort. The clinical profiles were quantified by the Yale-Brown obsessive-compulsive scale (Y-BOCS). Highly significant reductions in Y-BOCS scores were obtained from all patients during the follow-up period. A greater that 90% reduction in Y-BOCS, observed in the most successful case, was achieved with NAc HF-DBS. Y-BOCS scores in the other patients consistently achieved over 50% reductions in OCD symptoms. FDG-PET imaging indicated post-surgical reductions in metabolism, in not only targeted limbic networks, but also other frontal cortical and subcortical regions, suggesting that large-scale network modulation and inhibitions are associated with functional recovery in OCD. This study demonstrates that HF-DBS targeted to the ALIC and NAc is a safe and effective method for ameliorating intractable, treatment-refractory OCD symptoms. The NAc appeared to be the superior target for symptom reduction, and local inhibition of NAc activity and reduced frontal metabolism are key therapeutic indications.

Gamma Ventral Capsulotomy in Intractable Obsessive-Compulsive Disorder

BackgroundDespite the development of effective pharmacologic and cognitive behavioral treatments for obsessive-compulsive disorder (OCD), some patients continue to be treatment-refractory and severely impaired. Fiber tracts connecting orbitofrontal and dorsal anterior cingulate cortex with subcortical nuclei have been the target of neurosurgical lesions as well as deep brain stimulation in these patients. We report on the safety and efficacy of ventral gamma capsulotomy for patients with intractable OCD. MethodsFifty-five patients with severely disabling, treatment-refractory OCD received bilateral lesions in the ventral portion of the anterior limb of the internal capsule over a 20-year period using the Leksell Gamma Knife. The patients were prospectively followed over 3 years with psychiatric, neurologic, and neuropsychological assessments of safety and efficacy, as well as structural neuroimaging. ResultsThirty-one of 55 patients (56%) had an improvement in the primary efficacy measure, the Yale-Brown Obsessive Compulsive Scale, of ≥35% over the 3-year follow-up period. Patients had significant improvements in depression, anxiety, quality of life, and global functioning. Patients tolerated the procedure well without significant acute adverse events. Five patients (9%) developed transient edema that required short courses of dexamethasone. Three patients (5%) developed cysts at long-term follow-up, 1 of whom developed radionecrosis resulting in an ongoing minimally conscious state. ConclusionsGamma Knife ventral capsulotomy is an effective radiosurgical procedure for many treatment-refractory OCD patients. A minority of patients developed cysts at long-term follow-up, 1 of whom had permanent neurological sequelae.

Clinical Outcomes improvement of refractory Obsessive compulsive disorder by use Olanazapine

More than half of the patients with obsessive- compulsive disorder(OCD) remain unimproved by Serotonin-Reuptake inhibitors(SSRI). objective of this study was to examine whether addition of atypical antipsychotic (olanzapine ) to Sertraline is useful for patients with OCD who do not respond to SSRI monotherapy.1. According to (DSM IV-TR criteria) , 20 patients are diagnosed asOCD and did not responded to Sertraline at dose 100-150mg/day2. Olanazapine was additional treatment , start 2.5mg/day at first monththen 5 mg/day for last two months of study
 3. Treatment response was assessed using the Yale-Brown Obsessive- Compulsive Scale (YBOCS) at end of each months of study 16 of 20 patients respond to the olanzapine augmented sertraline therapy .
 The mean baseline YBOCS score of 32.75 dropped to a mean of 21.75 at endpoint for male with reduction 12.81% from baseline. While in female, the mean baseline YBOCS score of 33.83 dropped to amean of 21.67 at endpoint with reduction 17.06% from baseline. Treatment-refractory OCD Patients may benefit from addition of olanzapine to ongoing SSRI therapy.

Visuospatial Memory Improvement after Gamma Ventral Capsulotomy in Treatment Refractory Obsessive-Compulsive Disorder Patients.

Gamma ventral capsulotomy (GVC) radiosurgery is intended to minimize side effects while maintaining the efficacy of traditional thermocoagulation techniques for the treatment of refractory obsessive-compulsive disorder (OCD). Neuropsychological outcomes are not clear based on previous studies and, therefore, we investigated the effects of GVC on cognitive and motor performance. A double-blind, randomized controlled trial (RCT) was conducted with 16 refractory OCD patients allocated to active treatment (n=8) and sham (n=8) groups. A comprehensive neuropsychological evaluation including intellectual functioning, attention, verbal and visuospatial learning and memory, visuospatial perception, inhibitory control, cognitive flexibility, and motor functioning was applied at baseline and one year after the procedure. Secondary analysis included all operated patients: eight from the active group, four from the sham group who were submitted to surgery after blind was broken, and five patients from a previous open pilot study (n=5), totaling 17 patients. In the RCT, visuospatial memory (VSM) performance significantly improved in the active group after GVC (p=0.008), and remained stable in the sham group. Considering all patients operated, there was no decline in cognitive or motor functioning after one year of follow-up. Our initial results after 1 year of follow-up suggests that GVC not only is a safe procedure in terms of neuropsychological functioning but in fact may actually improve certain neuropsychological domains, particularly VSM performance, in treatment refractory OCD patients.

Morphometric brain characterization of refractory obsessive–compulsive disorder: Diffeomorphic anatomic registration using exponentiated Lie algebra

Few studies have used neuroimaging to characterize treatment-refractory obsessive-compulsive disorder (OCD). This study sought to explore gray matter structure in patients with treatment-refractory OCD and compare it with that of healthy controls. A total of 18 subjects with treatment-refractory OCD and 26 healthy volunteers were analyzed by MRI using a 3.0-T scanner and voxel-based morphometry (VBM). Diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL) was used to identify structural changes in gray matter associated with treatment-refractory OCD. A partial correlation model was used to analyze whether morphometric changes were associated with Yale-Brown Obsessive-Compulsive Scale scores and illness duration. Gray matter volume did not differ significantly between the two groups. Treatment-refractory OCD patients showed significantly lower gray matter density than healthy subjects in the left posterior cingulate cortex (PCC) and mediodorsal thalamus (MD) and significantly higher gray matter density in the left dorsal striatum (putamen). These changes did not correlate with symptom severity or illness duration. Our findings provide new evidence of deficits in gray matter density in treatment-refractory OCD patients. These patients may show characteristic density abnormalities in the left PCC, MD and dorsal striatum (putamen), which should be verified in longitudinal studies.

Long-term follow-up of patients with obsessive–compulsive disorder treated by anterior capsulotomy: A neuropsychological study

Background For treatment-refractory Obsessive–Compulsive-Disorder (OCD) patients, anterior capsulotomy is a potential therapy. We investigated what kinds of cognitive deficits treatment-refractory patients have and how anterior capsulotomy modifies their clinical and cognitive profiles. Methods Ten treatment-refractory OCD patients were examined in two groups (operated and non-operated) with 5 participants in each group, matched for symptom severity, gender, age and education. The operated group was treated with anterior capsulotomy; the non-operated group was treated only with pharmaco- and psychotherapy. The Yale–Brown Obsessive–Compulsive Rating Scale (Y-BOCS) was used to measure OCD symptoms, and ten neuropsychological tests were used to measure cognitive functioning. Results In the operated group, the score of Y-BOCS score significantly decreased during the two-year follow-up period. Additionally, we found a significant increase in neuropsychological test scores on the Wechsler Intelligence Test (MAWI), California Sorting Test Part A (CST-A), Stroop Test Interference Score (STR-I), Verbal Fluency Test and Iowa Gambling Test. As a negative result, we observed intrusion errors in the Category Fluency Test. In the non-operated group significant improvement was found in Y-BOCS scores. At follow-up, we found significant differences between the operated and non-operated groups on three neuropsychological tests: Trail Making Test Part B, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Attention Index and RBANS Language Index, with better performance in the non-operated group. Conclusions Both treatment methods (i.e. anterior capsulotomy and pharmaco- and psychotherapy) seem effective in reducing OCD symptoms and cognitive deficits, but, importantly, to different degrees. The clinical and neuropsychological improvements were more impressive in the operated group.

Quetiapine Augments the Effect of Citalopram in Non-Refractory Obsessive-Compulsive Disorder

To assess the efficacy of quetiapine addition to citalopram in treatment-naive or medication-free obsessive-compulsive disorder (OCD) patients. Seventy-six patients who met DSM-IV criteria for OCD and who were drug-free or drug-naive at entry were randomly assigned in a 10-week, double-blind trial with citalopram (60 mg/day) plus quetiapine (300-450 mg/day) or placebo; treatment-refractory OCD patients were excluded. Of the 76 eligible patients, 66 patients completed the trial-31 in the quetiapine and 35 in the placebo group. The change from baseline to endpoint on the total Yale-Brown Obsessive Compulsive Scale (YBOCS) and the response to treatment in the quetiapine addition compared with the placebo addition group were the primary outcome measures. Response was defined as a 35% or greater reduction on the YBOCS and a Clinical Global Impressions-Improvement (CGI-I) score at endpoint of 1 or 2. The study was conducted from November 2003 to June 2005 at the University Medical Centre Utrecht, The Netherlands. As measured by the mean reduction in YBOCS scores following an intent-to-treat, last-observation-carried-forward analysis, quetiapine addition (11.9) was significantly superior to placebo (7.8; p = .009). Quetiapine addition was also significantly superior to placebo on the CGI-I scale, with a mean +/- SD CGI-I score of 2.1 +/- 1.3 versus 1.4 +/- 1.2, respectively (p = .023). Quetiapine addition (N = 22, 69%) was also associated with a significantly greater number of patients responding to treatment compared with placebo addition (N = 15, 41%; p = .019). More patients receiving quetiapine (N = 8) than placebo (N = 2; NS) discontinued treatment due to adverse events. The combination of quetiapine and citalopram was more effective than citalopram alone in reducing OCD symptoms in treatment-naive or medication-free OCD patients. www.trialregister.nl Identifier NTR116.

“Contents May Vary”: A Pilot Study of Treatment Histories of OCD Patients

Definitions of treatment failure and the labelling of patients as non-responsive typically require treatments to have been offered and failed. For pharmacological treatments, treatment quality is relatively easy to define; this is much more difficult with psychological treatments. This study examined patient recollections of previous therapy for obsessive compulsive disorder (OCD). A Treatment History Questionnaire was administered to a sample of 57 apparently treatment refractory OCD patients from a specialist national OCD treatment unit and a national charity for OCD sufferers. On average, respondents reported an 8$\frac{1}{2}$ year wait between the obsessional symptoms interfering significantly with their lives and being diagnosed. Forty-three percent recalled having received either cognitive behaviour therapy (CBT) or behaviour therapy as the first treatment; 31% of the group did not know what type of therapy they had received. The components of therapy that respondents recalled were analysed and contrasted with minimal therapy criteria. These criteria appear not to have been met in most patients who understood that they had received “CBT”. The implications of this study for assessment of treatment integrity and the classification of patients as “treatment resistant” are discussed.

A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder

As many as half of obsessive-compulsive disorder (OCD) patients treated with an adequate trial of serotonin reuptake inhibitors (SRIs) fail to fully respond to treatment and continue to exhibit significant symptoms. Many studies have assessed the effectiveness of antipsychotic augmentation in SRI-refractory OCD. In this systematic review, we evaluate the efficacy of antipsychotic augmentation in treatment-refractory OCD. The electronic databases of PubMed, PsychINFO (1967-2005), Embase (1974-2000) and the Cochrane Central Register of Controlled Trials (CENTRAL, as of 2005, Issue 3) were searched for relevant double-blind trials using keywords 'antipsychotic agents' or 'neuroleptics' and 'obsessive-compulsive disorder'. Search results and analysis were limited to double-blind, randomized control trials involving the adult population. The proportion of subjects designated as treatment responders was defined by a greater than 35% reduction in Yale Brown Obsessive-Compulsive Scale (Y-BOCS) rating during the course of augmentation therapy. Nine studies involving 278 participants were included in the analysis. The meta-analysis of these studies demonstrated a significant absolute risk difference (ARD) in favor of antipsychotic augmentation of 0.22 (95% confidence interval (CI): 0.13, 0.31). The subgroup of OCD patients with comorbid tics have a particularly beneficial response to this intervention, ARD=0.43 (95% CI: 0.19, 0.68). There was also evidence suggesting OCD patients should be treated with at least 3 months of maximal-tolerated therapy of an SRI before initiating antipsychotic augmentation owing to the high rate of treatment response to continued SRI monotherapy (25.6%). Antipsychotic augmentation in SRI-refractory OCD is indicated in patients who have been treated for at least 3 months of maximal-tolerated therapy of an SRI. Unfortunately, only one-third of treatment-refractory OCD patients show a meaningful treatment response to antipsychotic augmentation. There is sufficient evidence in the published literature, demonstrating the efficacy of haloperidol and risperidone, and evidence regarding the efficacy of quetiapine and olanzapine is inconclusive. Patients with comorbid tics are likely to have a differential benefit to antipsychotic augmentation.

Clomipramine use in obsessive–compulsive disorder

The serotonin reuptake inhibitor, clomipramine and newer selective serotonin reuptake inhibitors have become recognized as the most effective monotherapy for obsessive–compulsive disorder. Meta-analyses have suggested that clomipramine may be superior to other selective serotonin reuptake inhibitors in treating obsessive–compulsive disorder. Double-blind, direct comparisons of the selective serotonin reuptake inhibitors and clomipramine, have demonstrated equal efficacy, fewer side effects and lower medication discontinuation rates in selective serotonin reuptake inhibitor patients. However, clomipramine continues to play a vital role in the pharmacotherapy of obsessive–compulsive disorder, being used when two or more selective serotonin reuptake inhibitor trials have not been sufficiently effective, which can occur in up to a third of patients. Recent investigation suggests potential roles for intravenous clomipramine and the combination of oral clomipramine with selective serotonin reuptake inhibitors and other medications in treatment-refractory obsessive–compulsive disorder patients.