Yale-Brown Obsessive Compulsive Scale Reduction Research Articles

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

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

An evaluation of treatment response and remission definitions in adult obsessive-compulsive disorder: A systematic review and individual-patient data meta-analysis

IntroductionExpert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. MethodsWe conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. ResultsIndividual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. ConclusionWhile the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.

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.

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

Deep brain stimulation (DBS) is a promising treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, nine participants (four females, mean age 47.9 ± 10.7 years) were implanted with DBS electrodes bilaterally in the bed nucleus of the stria terminalis (BNST). Following a one-month postoperative recovery phase, participants entered a three-month randomised, double-blind, sham-controlled phase before a twelve-month period of open-label stimulation incorporating a course of cognitive behavioural therapy (CBT). The primary outcome measure was OCD symptoms as rated with the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the blinded phase, there was a significant benefit of active stimulation over sham (p = 0.025, mean difference 4.9 points). After the open phase, the mean reduction in YBOCS was 16.6 ± 1.9 points (χ2 (11) = 39.8, p = 3.8 × 10−5), with seven participants classified as responders. CBT resulted in an additive YBOCS reduction of 4.8 ± 3.9 points (p = 0.011). There were two serious adverse events related to the DBS device, the most severe of which was an infection during the open phase necessitating device explantation. There were no serious psychiatric adverse events related to stimulation. An analysis of the structural connectivity of each participant’s individualised stimulation field isolated right-hemispheric fibres associated with YBOCS reduction. These included subcortical tracts incorporating the amygdala, hippocampus and stria terminalis, in addition to cortical regions in the ventrolateral and ventromedial prefrontal cortex, parahippocampal, parietal and extrastriate visual cortex. In conclusion, this study provides further evidence supporting the efficacy and tolerability of DBS in the region of the BNST for individuals with otherwise treatment-refractory OCD and identifies a connectivity fingerprint associated with clinical benefit.

Long-term Outcomes of Intensive Inpatient Care for Severe, Resistant Obsessive-Compulsive Disorder: Résultats à long terme de soins intensifs à des patients hospitalisés pour un trouble obsessionnel-compulsif grave et résistant.

A substantial proportion of severely ill patients with obsessive-compulsive disorder (OCD) do not respond to serotonin reuptake inhibitors (SRIs) and are unable to practice cognitive behavioral therapy (CBT) on an out-patient basis. We report the short-term (at discharge) and long-term (up to 2 years) outcome of a multimodal inpatient treatment program that included therapist-assisted intensive CBT with adjunctive pharmacotherapy for severely ill OCD patients who are often resistant to SRIs and are either unresponsive or unable to practice outpatient CBT. A total of 420 patients, admitted between January 2012 and December 2017 were eligible for the analysis. They were evaluated using the Mini International Neuropsychiatric Interview, the Yale-Brown Obsessive Compulsive Scale (YBOCS), and the Clinical Global Impression (CGI) scale. All patients received 4 to 5 therapist-assisted CBT sessions per week along with standard pharmacotherapy. Naturalistic follow-up information at 3, 6, 12, and 24 months were recorded. At baseline, patients were mostly severely ill (YBOCS = 29.9 ± 4.5) and nonresponsive to ≥2 SRIs (83%). Mean duration of inpatient stay was 42.7 ± 25.3 days. At discharge, there was a significant decline in the mean YBOCS score (29.9 ± 4.5 vs. 18.1 ± 7.7, P < .001, Cohen's d = 1.64); 211/420 (50%) were responders (≥35% YBOCS reduction and CGI-I≤2) and an additional 86/420 (21%) were partial responders (25% to 35% YBOCS reduction and CGI-I≤3). Using latent class growth modeling of the follow-up data, 4 distinct classes were identified, which include "remitters" (14.5%), "responders" (36.5%), "minimal responders" (34.7%), and "nonresponders" (14.6%). Shorter duration of illness, better insight, and lesser contamination/washing symptoms predicted better response in both short- and long-term follow-up. Intensive, inpatient-based care for OCD may be an effective option for patients with severe OCD and should be considered routinely in those who do not respond with outpatient treatment.

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.

Open-label trial of anterior limb of internal capsule–nucleus accumbens deep brain stimulation for obsessive-compulsive disorder: insights gained

BackgroundFor more than 15 years, deep brain stimulation (DBS) has served as a last-resort treatment for severe treatment-resistant obsessive-compulsive disorder (OCD).MethodsFrom 2010 to 2016, 20 patients with OCD (10 men/10...

Novel ensemble method for the prediction of response to fluvoxamine treatment of obsessive-compulsive disorder.

ObjectiveAbout 30% of obsessive–compulsive disorder (OCD) patients exhibit an inadequate response to pharmacotherapy. The detection of clinical variables associated with treatment response may result in achievement of remission in shorter period, preventing illness development and reducing socioeconomic costs.MethodsIn total, 330 subjects with OCD diagnosis underwent 12-week pharmacotherapy with fluvoxamine (150–300 mg). Treatment response was ≥25% reduction in Yale-Brown Obsessive–Compulsive Scale (Y-BOCS) score. In total, 36 clinical attributes of 151 subjects who had completed their treatment course were analyzed. Data mining algorithms included missing value handling, feature selection, and new analytical method based on ensemble classification. The results were compared with those of other traditional classification algorithms such as decision tree, support vector machines, k-nearest neighbor, and random forest.ResultsSexual and contamination obsessions are high-ranked predictors of resistance to fluvoxamine pharmacotherapy as well as high Y-BOCS obsessive score. Our results showed that the proposed analysis strategy has good ability to distinguish responder and nonresponder patients according to their clinical features with 86% accuracy, 79% sensitivity, and 89% specificity.ConclusionThis study proposed an analytical approach which is an accurate and a sensitive method for the analysis of high-dimensional medical data sets containing more number of missing values. The treatment of OCD could be improved by better understanding of the predictors of pharmacotherapy, which may lead to more effective treatment of patients with OCD.

Augmentation in profound, SRI-refractory OCD: Is aripiprazole superior to other to other dopamine blockers?

IntroductionOCD is a common disorder, affecting 1% of the population and usually responds to treatment with serotonin reuptake inhibitors (SRIs) or exposure and response prevention (ERP) and to augmentation with antipsychotics. However, some patients fail to respond. The national inpatient unit for obsessive compulsive disorder (OCD) and body dysmorphic disorder (BDD) (i) is the only 24-hour staffed inpatient facility for OCD in the UK and treats patients with profound, treatment-refractory OCD. There is evidence of efficacy of aripiprazole in augmenting SRI sin severe OCD (ii).ObjectivesTo compare the efficacy of aripiprazole versus other antipsychotics as SRI augmentation.MethodsOne hundred and nine patients admitted to the unit between March 2006 and September 2011 and discharged on an antipsychotic and an SRI were included. The Yale-Brown obsessive compulsive scale (YBOCS) was administered at admission and at discharge. Data were analysed using SPSS version 23 using analysis of variance (ANOVA). Two groups were compared: those receiving SRI + aripiprazole versus those receiving SRI + another antipsychotic.Resultssixty-two patients received SRI with aripiprazole and 47 SRIs with another antipsychotic. Overall, patients showed improvement, with an average YBOCS reduction of 11.7 (33% reduction). Patients taking aripiprazole improved by an average of 13 (36% reduction, P &lt; 0.05).ConclusionsPatients of the national unit with severe, treatment refractory OCD treated with aripiprazole augmentation showed a greater improvement than those on other antipsychotics. Further research into aripiprazole in OCD is warranted.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Six-Nine Year Follow-Up of Deep Brain Stimulation for Obsessive-Compulsive Disorder.

ObjectiveDeep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) region has shown promise as a neurosurgical intervention for adults with severe treatment-refractory obsessive-compulsive disorder (OCD). Pilot studies have revealed improvement in obsessive-compulsive symptoms and secondary outcomes following DBS. We sought to establish the long-term safety and effectiveness of DBS of the VC/VS for adults with OCD.Materials and MethodsA long term follow-up study (73–112 months) was conducted on the six patients who were enrolled in the original National Institute of Mental Health pilot study of DBS for OCD. Qualitative and quantitative data were collected.ResultsReduction in OCD symptoms mirrored the one-year follow-up data. The same four participants who were treatment responders after one year of treatment showed a consistent OCD response (greater than 35% reduction in Yale Brown Obsessive Compulsive Scale (YBOCS)). Another subject, classified as a non-responder, achieved a 26% reduction in YBOCS score at long term follow-up. The only patient who did not achieve a 25% or greater reduction in YBOCS was no longer receiving active DBS treatment. Secondary outcomes generally matched the one-year follow-up with the exception of depressive symptoms, which significantly increased over the follow-up period. Qualitative feedback indicated that DBS was well tolerated by the subjects.DiscussionThese data indicate that DBS was safe and conferred a long-term benefit in reduction of obsessive-compulsive symptoms. DBS of the VC/VS region did not reveal a sustained response for comorbid depressive symptoms in patients with a primary diagnosis of OCD.

Aripiprazole Addition to Serotonin Reuptake Inhibitor in Treatment-Resistant Obsessive-Compulsive Disorder

Background: As is well-known, serotonin-reuptake inhibitors (SRIs) are unsuccessful in management of forty to sixty percent of patients suffering from obsessivecompulsive disorder (OCD). So, purpose of the present trial was to assess that whether addon aripiprazole, as adjunctive to SRIs, is helpful in cases with treatment-resistant OCD. Method: In an Open-prospective, single-arm interventional study with blinded rating, sixteen patients with OCD, who had not improved noticeably by serotonin-reuptake inhibitors, after maximum dosage and period, were allocated to get aripiprazole plus their SRIs for eight weeks. Management outcome was measured by means of the Yale-Brown Obsessive Compulsive Scale (YBOCS). Complete reaction to the abovementioned augmentative therapy was demarcated of at least fifty percent reduction in YBOCS’ score and partial reaction as equivalent to or >25% - <50% reduction in YBOCS in comparison with the starting point. Results: Neither of patients responded with at least 25% decrease in YBOCS score to the aripiprazole addition (20 mg/day). 18% of cases experienced a reduction between 10-20%, and 68% of them less than 10%. Two patients did not show any change at all. The mean+/-SD baseline YBOCS’ score of 35.2 +/- 2.9 dropped to a mean of 32.8 +/- 4.1 at endpoint with a mean reduction of 8.8+/- 7.8% (p<0.06). Conclusion: Within the limits of statistical power, this assessment does not offer additional proof that adding of aripiprazole to current SRI treatment could be worthwhile for cases suffering from treatment-resistant OCD. Keywords: Antipsychotic, aripiprazole, obsessive-compulsive disorder, treatment resistant.

Intensive residential treatment for severe obsessive-compulsive disorder: Characterizing treatment course and predictors of response

BackgroundIntensive residential treatment (IRT) is effective for severe, treatment-resistant obsessive-compulsive disorder (OCD). We sought to characterize predictors and course of response to IRT. MethodsAdmission, monthly, and discharge data were collected on individuals receiving IRT. We examined the association between baseline characteristics and percent change in OCD symptoms as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) using linear regression. We compared baseline characteristics of IRT responders (≥35% reduction in Y-BOCS) versus non-responders, and of patients who did versus those who did not achieve wellness (Y-BOCS ≤ 12) using non-parametric tests. To examine the course of OCD severity over time, we used linear mixed-effects models with randomly varying intercepts and slopes. ResultsWe evaluated 281 individuals admitted to an IRT program. Greater baseline Y-BOCS scores were associated with a significantly greater percent reduction in Y-BOCS scores (β = −1.49 ([95% confidence interval: −2.06 to −0.93]; P < .001)). IRT responders showed significantly greater baseline Y-BOCS scores than non-responders (mean (SD) 28 (5.2) vs. 25.6 (5.8); P = .003) and lower past-year alcohol use scores than non-responders (1.4 (1.9) vs. 2.1 (2.2); P = .01). Participants who achieved wellness displayed lower hoarding factor scores than those who did not (5 (4.6) vs. 9.53 (6.3); P = .03). OCD symptoms declined rapidly over the first month but more slowly over the remaining two months. ConclusionsHigher baseline OCD severity, lower past-year alcohol use, and fewer hoarding symptoms predicted better response to IRT. IRT yielded an initial rapid reduction in OCD symptoms, followed by a slower decline after the first month.

Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept

Serotonin reuptake inhibitors (SRIs), the first-line pharmacological treatment for obsessive-compulsive disorder (OCD), have two limitations: incomplete symptom relief and 2-3 months lag time before clinically meaningful improvement. New medications with faster onset are needed. As converging evidence suggests a role for the glutamate system in the pathophysiology of OCD, we tested whether a single dose of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, could achieve rapid anti-obsessional effects. In a randomized, double-blind, placebo-controlled, crossover design, drug-free OCD adults (n=15) with near-constant obsessions received two 40-min intravenous infusions, one of saline and one of ketamine (0.5 mg/kg), spaced at least 1-week apart. The OCD visual analog scale (OCD-VAS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) were used to assess OCD symptoms. Unexpectedly, ketamine's effects within the crossover design showed significant (p<0.005) carryover effects (ie, lasting longer than 1 week). As a result, only the first-phase data were used in additional analyses. Specifically, those receiving ketamine (n=8) reported significant improvement in obsessions (measured by OCD-VAS) during the infusion compared with subjects receiving placebo (n=7). One-week post-infusion, 50% of those receiving ketamine (n=8) met criteria for treatment response (≥35% Y-BOCS reduction) vs 0% of those receiving placebo (n=7). Rapid anti-OCD effects from a single intravenous dose of ketamine can persist for at least 1 week in some OCD patients with constant intrusive thoughts. This is the first randomized, controlled trial to demonstrate that a drug affecting glutamate neurotransmission can reduce OCD symptoms without the presence of an SRI and is consistent with a glutamatergic hypothesis of OCD.

High-dose escitalopram for the treatment of obsessive–compulsive disorder

The aim of this study was to evaluate the efficacy and tolerability of high-dose escitalopram in patients suffering from obsessive-compulsive disorder (OCD). In an open-label, 16-week prospective study, patients with OCD received escitalopram at a dose of 20 mg/day for 3 weeks, after a 1-week titration at 10 mg/day. Patients who did not achieve a > or =25% reduction from baseline in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score during these 4 weeks were continued on higher doses of escitalopram (maximum 50 mg/day) for 12 weeks. The primary efficacy measure of OCD symptoms was change from baseline in the Y-BOCS score. Overall, 67 patients (33 women, 34 men) with a mean Y-BOCS score of 29.6 entered the study. After 4 weeks of standard-dose escitalopram treatment, one patient discontinued owing to pregnancy, and two patients achieved a reduction in Y-BOCS > or =25%. Consequently, 64 patients were eligible to receive high-dose escitalopram (mean dose, 33.8 mg/day at endpoint). At endpoint, high-dose escitalopram had significantly improved the OCD symptoms (Y-BOCS score) and all the other efficacy measures (P<0.001), compared with baseline. Escitalopram was also well tolerated, with no discontinuations during the 12-week high-dose phase. The only reported adverse drug reactions were dry mouth (n=8, 12.1%) and decreased sexual desire (n=21, 31.8%). Preliminary investigation shows that high-dose escitalopram is an efficacious and well tolerated treatment for patients suffering from severe OCD. Randomized, blinded studies are needed to reinforce these findings.

Cognitive‐Behavioral Treatment of Pediatric Obsessive‐Compulsive Disorder: An Open Clinical Trial

The purpose of this open clinical trial was to examine the efficacy of cognitive-behavioral treatment involving exposure and ritual prevention for pediatric obsessive-compulsive disorder (OCD). Children and adolescents with diagnosed OCD (N = 14) received cognitive-behavioral treatment, seven patients received intensive treatment (mean = 18 sessions over 1 month) and seven received weekly treatment (mean = 16 sessions over 4 months). Eight of these patients received concurrent treatment with serotonin reuptake inhibitors and six received cognitive-behavioral treatment alone. Outcome was assessed via interviewer ratings on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Obsessive Compulsive Rating Scales for Main Fear and Main Ritual, and Hamilton Depression Rating Scale. Cognitive-behavioral treatment was effective in ameliorating OCD symptoms. Twelve of the 14 patients were at least 50% improved over pretreatment Y-BOCS severity, and the vast majority remained improved at follow-up; mean reduction in Y-BOCS was 67% at posttreatment and 62% at follow-up (mean time to follow-up = 9 months). Results suggest that cognitive-behavioral treatment by exposure and ritual prevention is effective for pediatric OCD. Controlled studies with random assignment to conditions are warranted to evaluate the relative efficacy of cognitive-behavioral pharmacological, and combined treatments.