Decrease In Yale-Brown Obsessive Compulsive Scale Research Articles

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

A preliminary study into the effects of the COVID-19 pandemic on Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores of patients with obsessive compulsive disorder

AimsThe COVID-19 pandemic has presented a challenge for treating people with OCD and it could be postulated that those with OCD fearing contamination might be more affected in current circumstances. Although there have been some studies already published, results have been heterogeneous and conflicting; possibly because of different populations or geographical locations examined.In this preliminary study we aim to identify the impact of the pandemic on the severity of OCD, as measured by Y-BOCS scores. To our knowledge, it is the first UK study of this kind and the only study that examines change in Y-BOCS scores over such a long time period.MethodPatients were identified from national OCD unit referral databases at Springfield Hospital. Referrals from March 2019–March 2020 were examined and patients included if they had a diagnosis of OCD, were accepted by the service following initial assessment and sufficient data were available. This preliminary study focused only on Y-BOCS to assess clinician-rated severity of OCD. Y-BOCS scores were compared from different time periods correlating to the progression of COVID-19. ‘Pre-pandemic’ score was taken from Jan–Dec 2019 or, if not available, from Jan–23 March 2020 (prior to UK lockdown). ‘Pandemic’ score was taken as the most recent rating from April 2020 onwards.Result21 patients were included. All treated as outpatients (although 9 had undergone previous inpatient treatment during the time period above). 81% showed improvement in Y-BOCS score between pre-pandemic and pandemic time periods, with an overall mean decrease in Y-BOCS of 10.3.ConclusionOverall, this study indicates that severity of OCD decreased during the pandemic compared to pre-pandemic. It may be that patients found it easier to access remote appointments, or perhaps the pandemic environment of being encouraged to stay at home and limiting unnecessary contact may have allowed limited opportunity for exposure. It might be that the pandemic provided a reason for patients to be avoidant of potential contamination thereby leading to a perceived rather than real improvement in Y-BOCS scores.Identification of specific contributing factors is beyond the scope of this preliminary study, however it will be important to conduct further research with a larger sample size that incorporates post-lockdown and post-pandemic scores to ascertain whether trends seen here are in fact maintained when normal social contact resumes.

Deep Brain Stimulation in the Bed Nucleus of Stria Terminalis in Obsessive-Compulsive Disorder—1-Year Follow-up

Deep brain stimulation (DBS) is under investigation as a treatment for therapy-refractory obsessive-compulsive disorder (OCD). As a crucial part of the anxiety circuit, the bed nucleus of stria terminalis (BNST) has been proposed as a target for DBS in OCD. Here, we investigate clinical outcomes and safety of DBS in the BNST in a series of 11 participants with severe therapy-refractory OCD. Eleven consecutive participants diagnosed with refractory OCD were treated with BNST DBS and completed follow-up. The primary outcome was a change in scores of the Yale Brown Obsessive Compulsive Scale (YBOCS) at 1 year after surgery. Secondary outcomes included changes in scores of the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Global Assessment of Functioning. At baseline, the mean ± SD YBOCS score was 33 ± 3.0, MADRS score was 29 ± 4.5, and GAF score was 49 ± 5.4. One year after DBS, mean ± SD YBOCS score was 20 ± 4.8 (38% improvement (range 10%-60%) P<0.01),MADRS score was 21 ± 5.8 (27% improvement, range 4%-74%, P < 0.01), and Global Assessment of Functioning score was 55 ± 6.5 (12% improvement, range 4%-29%, P<0.05). Of the 11 participants, 6 were considered responders (decrease in YBOCS ≥35%) and 4 partial responders (decrease in YBOCS 25%-34%). Surgical adverse events included 1 case of skin infection leading to reimplantation. The most common transient stimulation-related side effects were anxiety and insomnia. BNST DBS is a promising therapy in severe therapy-refractory OCD. Our results are in line with previous publications regarding effect and safety profile. Nevertheless, DBS for OCD remains an investigational therapy and should therefore be performed in multidisciplinary clinical studies.

Integrating Exposure and Response Prevention With a Mobile App to Treat Obsessive-Compulsive Disorder: Feasibility, Acceptability, and Preliminary Effects

Many individuals with obsessive-compulsive disorder (OCD) do not receive evidence-based care (specifically exposure and ritual prevention; EX/RP) due to barriers such as a lack of EX/RP-trained clinicians, geographic obstacles, and the cost and time associated with the treatment. Offering an integrated treatment model consisting of brief in-person therapy coupled with a mobile application (app) might be one way to increase access to and reduce the time burden (to clinicians and patients) of EX/RP. This pilot trial evaluated the feasibility, acceptability, and clinical effects of such a treatment program for adults with OCD. Thirty-three participants enrolled in the 8-week open trial. The integrated treatment program consisted of 3 to 5 in-person sessions followed by weekly phone calls supported by a mobile app (nOCD). Participants were evaluated by trained raters and completed self-report measures at baseline, midtreatment, posttreatment and 2-month follow-up; the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was the primary outcome. This integrated treatment program was feasible and acceptable to participants. Of the 33 study entrants, 14 (42%) responded to treatment (Y-BOCS decrease ≥35% with CGI- of 1 or 2), and 8 (24%) achieved minimal symptoms (i.e., Y-BOCS ≤12). At 2-month follow-up (n=20), 7/20 (35%) met criteria for treatment response, and 3/20 (15.0%) met criteria for treatment remission. Although preliminary, this model warrants further study as an efficacious and resource-efficient way to deliver EX/RP for some patients with OCD.

A Systematic Review of Evidence-based Treatment Strategies for Obsessive- compulsive Disorder Resistant to first-line Pharmacotherapy.

Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). However, a significant proportion of patients do not respond satisfactorily to first-choice treatments. Several options have been investigated for the management of resistant patients. The aim of the present paper is to systematically review the available literature concerning the strategies for the treatment of resistant adult patients with OCD. We first reviewed studies concerning the definition of treatment-resistant OCD; we then analyzed results of studies evaluating several different strategies in resistant patients. We limited our review to double-blind, placebo-controlled studies performed in adult patients with OCD whose resistance to a first adequate (in terms of duration and dosage) SRI trial was documented and where outcome was clearly defined in terms of decrease in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores and/or response/ remission rates (according to the YBOCS). We identified five strategies supported by positive results in placebo-controlled randomized studies: 1) antipsychotic addition to SRIs (16 RCTs, of them 10 positive; 4 head-to-head RCTs); among antipsychotics, available RCTs examined the addition of haloperidol (butyrophenone), pimozide (diphenyl-butylpiperidine), risperidone (SDA: serotonin- dopamine antagonist), paliperidone (SDA), olanzapine (MARTA: multi-acting receptor targeted antipsychotic), quetiapine (MARTA) and aripiprazole (partial dopamine agonist); 2) CBT addition to medication (2 positive RCTs); 3) switch to intravenous clomipramine (SRI) administration (2 positive RCTs); 4) switch to paroxetine (SSRI: selective serotonin reuptake inhibitor) or venlafaxine (SNRI: serotonin-norepinephrine reuptake inhibitor) when the first trial was negative (1 positive RCT); and 5) the addition of medications other than an antipsychotic to SRIs (18 RCTs performed with several different compounds, with only 4 positive studies). Treatment-resistant OCD remains a significant challenge to psychiatrists. To date, the most effective strategy is the addition of antipsychotics (aripiprazole and risperidone) to SRIs; another effective strategy is CBT addition to medications. Other strategies, such as the switch to another first-line treatment or the switch to intravenous administration are promising but need further confirmation in double-blind studies. The addition of medications other than antipsychotics remains to be studied, as several negative studies exist and positive ones need confirmation (only 1 positive study).

Paroxetine concentrations in obsessive-compulsive disorder: Support for a therapeutic interval

IntroductionPrevious studies of concentrations of serotonin reuptake inhibitors (SRIs) versus therapeutic efficacy have yielded inconsistent results. Even if the relationships between the individual's serotonergic system and the clinical symptoms of obsessive-compulsive disorder (OCD) are poorly understood, the SRIs are consistently effective in OCD. However, studies on SRI concentrations in OCD treatment are rare.Objectives/aimsTo identify possible links between paroxetine concentrations and anti-obsessive response.MethodsIn a randomised, double-blind trial, comparing clomipramine, paroxetine and placebo in OCD treatment, serum paroxetine levels were measured after 1 week and after 4 weeks of treatment in 18 patients. Anti-obsessive response was assessed with Yale-Brown obsessive compulsive scale (Y-BOCS) and patients’ global evaluation (PGE), after 12 weeks of treatment.ResultsSerum paroxetine concentrations after 4 weeks suggested a therapeutic interval between 50 and 240 nmol/L (13–63 ng/mL). The mean Y-BOCS decrease was 54% inside versus 7% outside this interval (t = 3.96; P = 0.0011).ConclusionsParoxetine levels seemingly predicted clinical outcome. Studies with a greater number of patients are necessary in order to confirm this finding and to discern whether it is useful in clinical practice.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Network Meta-Analysis of the Relative Efficacy of Pharmacological and Psychological Interventions in Adults with Obsessive Compulsive Disorder.

Obsessive compulsive disorder (OCD) is the fourth most common mental disorder in the UK with a prevalence of 1.5%. Both pharmacological and psychological interventions are used in the treatment with the treatment course usually chronic. This study estimates the relative efficacy of pharmacological and psychological treatments or combinations of both. A systematic review was conducted to identify RCTs of clomipramine, SSRIs, venlafaxine, and psychological interventions with a behavioural, cognitive or cognitive behavioural component. A Bayesian random effects network meta-analyses (NMA) was used to obtain coherent estimates of relative efficacy of every pair of the different interventions, even when direct evidence was not available. The primary endpoint was mean change in Yale-Brown obsessive compulsive scale (YBOCS). We assumed that treatment effects for the different SSRIs were similar in the sense that they came from a common Normal distribution of treatment effects with an overall SSRI class effect mean, and between treatment within class heterogeneity. There were 55 eligible studies identified in the systematic review. The intervention with the greatest decrease in YBOCS was behavioural therapy (“exposure and response prevention”) showing a decrease of 13.86 (CrI 9.34 to 18.31). The second and third greatest decrease was cognitive therapy (12.80 CrI 7.39 to 18.18) and behavioural therapy plus clomipramine (12.47 CrI 5.80 to 19.08) respectively. The SSRI class effect showed a relative decrease in mean YBOCS of 2.89 (CrI 1.05 to 4.71) compared to pharmacological placebo. The Results of the individual SSRIs ranged from a decrease of 2.49 (sertraline) to 3.10 (fluvoxamine). This analysis showed a combination of behavioural therapy plus clomipramine has the greatest decrease in YBOCS. There is little evidence to show a difference between SSRIs.