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Introduction: Expert 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., Methods: We 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., Results: Individual 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., Conclusion: While 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., Competing Interests: Declaration of competing interest Abraham Zangen is an inventor of Deep TMS coils developed to study and treat neurological and psychiatric disorders and has financial interest in BrainsWay which produces and markets these coils. Daniel L.C. Costa received honoraria from Janssen, Lundbeck and Schwabe pharmaceuticals. David Mataix-Cols receives royalties for contributing articles to UpToDate, Inc. David Shannahoff-Khalsa reports royalties from two books published by W.W. Norton & Co, Inc. that includes the Kundalini Yoga meditation protocol, personal sales for a DVD for the protocol, and OCD patient fees. Eric A. Storch receives research funding for his institution from the Ream Foundation, International OCD Foundation, and NIH. He is a consultant for Brainsway and Biohaven Pharmaceuticals. He owns stock less than $5000 in NView (for distribution of the Y-BOCS and CY-BOCS) and Limbix. He receives book royalties from Elsevier, Wiley, Oxford, American Psychological Association, Guildford, Springer, Routledge, and Jessica Kingsley. Juliana B. Diniz has received speaker's fees from Lundbeck and Janssen Cilag for lectures. Michael H. Bloch has received grant/research support from Therapix Biosciences, Emalex Biosciences, Janssen Pharmaceuticals, Biohaven Pharmaceuticals, NIH, Lesbian Health Fund, Yale Foundation for Lesbian and Gay Studies (FLAGS), and Patterson Foundation, has served on the advisory board/data monitoring and safety board of Therapix Biosciences, and serves as associate editor of Journal of Child Psychology and Psychiatry and on the editorial boards of Journal of Child and Adolescent Psychopharmacology and Depression & Anxiety. He has received royalties from Wolters Kluwer for Lewis's Child and Adolescent Psychiatry: A Comprehensive Textbook, Fifth Edition and moonlighting pay from the VA. Roseli G. Shavitt has received consultancy honoraria from Lundbeck and research grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) in the past three years. Sabine Wilhelm is a presenter for the Massachusetts General Hospital Psychiatry Academy in educational programs supported through independent medical education grants from pharmaceutical companies. She has received royalties from Elsevier Publications, Guilford Publications, New Harbinger Publications, Springer, and Oxford University Press, speaking honoraria from various academic institutions and foundations, including the International Obsessive Compulsive Disorder Foundation, the Tourette Association of America, and the Centers for Disease Control and Prevention, and payment from the Association for Behavioral and Cognitive Therapies for her role as Associate Editor of the Behavior Therapy journal and John Wiley & Sons, Inc. as Associate Editor of the journal Depression & Anxiety. She has also received honoraria for her role on the Scientific Advisory Board for One-Mind (PsyberGuide), Koa Health, Inc, and Noom, Inc. She has received research and salary support from Koa Health, Inc. None of the remaining co-authors have any conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To summarize the evidence-based cognitive-behavioral therapy (CBT) treatment and propose clinical interventions for adult patients with obsessive-compulsive disorder (OCD)., Methods: A systematic review of the literature on CBT interventions for the treatment of adult OCD, comprising behavior therapy and exposure and response prevention (ERP) was done. The objective of this study is to present updated clinical guidelines to clinicians, providing comprehensive details regarding the necessary procedures to be incorporated into the CBT protocol. We searched the literature published from 2013-2020 in five databases (PubMed, Cochrane, Embase, Psycinfo and Lilacs), considering: study design, primary outcome measures, type of publication and language. Selected articles were assessed for quality with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association (ACC/AHA)., Results: We examined 44 new studies used to update the APA guidelines from 2013. High-quality evidence supports CBT including ERP techniques as the first-line CBT treatment for OCD. In addition, protocols for internet-delivered CBT have also demonstrated their efficacy for the treatment of adults with OCD., Conclusion: CBT based on ERP is a widely used treatment according to high-quality scientific evidence to treat adults with OCD., Competing Interests: The authors report no conflicts of interest.

Objectives: To summarize evidence-based pharmacological treatments and provide guidance on clinical interventions for adult patients with obsessive-compulsive disorder (OCD)., Methods: The American Psychiatric Association (APA) guidelines for the treatment of OCD (2013) were updated with a systematic review assessing the efficacy of pharmacological treatments for adult OCD, comprising monotherapy with selective serotonin reuptake inhibitors (SSRIs), clomipramine, serotonin and norepinephrine reuptake inhibitors (SNRIs), and augmentation strategies with clomipramine, antipsychotics, and glutamate-modulating agents. We searched for the literature published from 2013-2020 in five databases, considering the design of the study, primary outcome measures, types of publication, and language. Selected articles had their quality assessed with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association (ACC/AHA)., Results: We examined 57 new studies to update the 2013 APA guidelines. High-quality evidence supports SSRIs for first-line pharmacological treatment of OCD. Moreover, augmentation of SSRIs with antipsychotics (risperidone, aripiprazole) is the most evidence-based pharmacological intervention for SSRI-resistant OCD., Conclusion: SSRIs, in the highest recommended or tolerable doses for 8-12 weeks, remain the first-line treatment for adult OCD. Optimal augmentation strategies for SSRI-resistant OCD include low doses of risperidone or aripiprazole. Pharmacological treatments considered ineffective or potentially harmful, such as monotherapy with antipsychotics or augmentation with ketamine, lamotrigine, or N-acetylcysteine, have also been detailed., Competing Interests: The authors report no conflicts of interest.

Objective: A lack of universal definitions for response and remission in pediatric obsessive-compulsive disorder (OCD) has hampered the comparability of results across trials. To address this problem, we conducted an individual participant data diagnostic test accuracy meta-analysis to evaluate the discriminative ability of the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) in determining response and remission. We also aimed to generate empirically derived cutoffs on the CY-BOCS for these outcomes., Method: A systematic review of PubMed, PsycINFO, Embase and CENTRAL identified 5,401 references; 42 randomized controlled clinical trials were considered eligible, and 21 provided data for inclusion (N = 1,234). Scores of ≤2 in the Clinical Global Impressions Improvement and Severity scales were chosen to define response and remission, respectively. A 2-stage, random-effects meta-analysis model was established. The area under the curve (AUC) and the Youden Index were computed to indicate the discriminative ability of the CY-BOCS and to guide for the optimal cutoff, respectively., Results: The CY-BOCS had sufficient discriminative ability to determine response (AUC = 0.89) and remission (AUC = 0.92). The optimal cutoff for response was a ≥35% reduction from baseline to posttreatment (sensitivity = 83.9, 95% CI = 83.7-84.1; specificity = 81.7, 95% CI = 81.5-81.9). The optimal cutoff for remission was a posttreatment raw score of ≤12 (sensitivity = 82.0, 95% CI = 81.8-82.2; specificity = 84.6, 95% CI = 84.4-84.8)., Conclusion: Meta-analysis identified empirically optimal cutoffs on the CY-BOCS to determine response and remission in pediatric OCD randomized controlled clinical trials. Systematic adoption of standardized operational definitions for response and remission will improve comparability across trials for pediatric OCD., (Copyright © 2021 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Differences in hippocampus volume have been identified in adult patients with obsessive-compulsive disorder (OCD). However, the role of this limbic structure in pediatric patients is unclear. This study aimed to investigate the hippocampus and its subregions in a sample of 29 children and adolescents with OCD compared to 28 healthy controls, matched for age, sex, education, and IQ. Volumetric segmentation was performed using the Freesurfer software to calculate the volumes of the subregions that reflect the hippocampal cytoarchitecture. The volumes of three anatomic subregions (tail, body, and head) were also calculated. ANCOVA was performed to investigate differences of these volumes between patients and controls, controlling for total gray matter volume. After Bonferroni correction for multiple comparisons (p-value < 0.00556 for the body and < 0.00625 for the head structures), patients presented statistically significant larger volumes of the following structures: left subiculum body; left CA4 body; left GC-DG body; left molecular layer body; right parasubiculum; left CA4 head; left molecular layer head; right subiculum head and right molecular layer head. These enlarged volumes resulted in larger left and right whole hippocampi in patients, as well as bilateral hippocampal heads and left hippocampal body (all p-values < 0.00625). There were no associations between OCD severity and hippocampal volumes. These findings diverge from previous reports on adults and may indicate that larger hippocampal volumes could reflect an early marker of OCD, not present in adults., (Copyright © 2020. Published by Elsevier B.V.)

Treatment response in obsessive-compulsive disorder (OCD) is heterogeneous and the neurobiological underpinnings of such variability are unknown. To investigate this issue, we looked for differences in brain structures possibly associated with treatment response in children with OCD. 29 children with OCD (7-17 years) and 28 age-matched controls underwent structural magnetic resonance imaging. Patients then received treatment with fluoxetine or group cognitive-behavioral therapy during 14 weeks, and were classified as treatment responders or non-responders. The caudate nucleus, thalamus and orbitofrontal cortex were selected a priori, according to previous evidence of their association with OCD and its treatment. Gray matter (GM) volume comparisons between responders, non-responders and controls were performed, controlling for total GM volume. 17 patients were classified as responders. Differences among responders, non-responders and controls were found in both caudate nuclei (both p-values = 0.041), but after Bonferroni correction for multiple comparisons, these findings were non-significant. However, after excluding the effect of an outlier, findings were significant for the right caudate (p = 0.004). Pairwise comparisons showed larger caudate GM volume in responders versus non-responders and controls, bilaterally. The right caudate accounted for 20.2% of the variance in Y-BOCS changes after treatment in a linear regression model, with a positive correlation (p = 0.016). We present a possible neural substrate for treatment response in pediatric OCD, which is in line with previous evidence regarding the caudate nucleus. Considering the limitations, further research is needed to replicate this finding and elucidate the heterogeneity of treatment response in children with OCD (National Clinical Trials Registration Number: NCT01148316).

For more than half a century, stereotactic neurosurgical procedures have been available to treat patients with severe, debilitating symptoms of obsessive-compulsive disorder (OCD) that have proven refractory to extensive, appropriate pharmacological, and psychological treatment. Although reliable predictors of outcome remain elusive, the establishment of narrower selection criteria for neurosurgical candidacy, together with a better understanding of the functional neuroanatomy implicated in OCD, has resulted in improved clinical efficacy for an array of ablative and non-ablative intervention techniques targeting the cingulum, internal capsule, and other limbic regions. It was against this backdrop that gamma knife capsulotomy (GKC) for OCD was developed. In this paper, we review the history of this stereotactic radiosurgical procedure, from its inception to recent advances. We perform a systematic review of the existing literature and also provide a narrative account of the evolution of the procedure, detailing how the procedure has changed over time, and has been shaped by forces of evidence and innovation. As the procedure has evolved and adverse events have decreased considerably, favorable response rates have remained attainable for approximately one-half to two-thirds of individuals treated at experienced centers. A reduction in obsessive-compulsive symptom severity may result not only from direct modulation of OCD neural pathways but also from enhanced efficacy of pharmacological and psychological therapies working in a synergistic fashion with GKC. Possible complications include frontal lobe edema and even the rare formation of delayed radionecrotic cysts. These adverse events have become much less common with new radiation dose and targeting strategies. Detailed neuropsychological assessments from recent studies suggest that cognitive function is not impaired, and in some domains may even improve following treatment. We conclude this review with discussions covering topics essential for further progress of this therapy, including suggestions for future trial design given the unique features of GKC therapy, considerations for optimizing stereotactic targeting and dose planning using biophysical models, and the use of advanced imaging techniques to understand circuitry and predict response. GKC, and in particular its modern variant, gamma ventral capsulotomy, continues to be a reliable treatment option for selected cases of otherwise highly refractory OCD.

Black esophagus is a rare but underdiagnosed disease. It occurs most frequently in severely ill patients and carries a high mortality rate. Cause of death is usually attributed to the comorbid conditions. Treatment is directed at the underlying cause, acid suppression and keeping the patient nil-per-os. Surgery is needed in complicated cases and stenosis is the most feared longterm sequel. In the present article, two cases are described and literature is reviewed., Competing Interests: Conflict of interest: None