Treatment-resistant OCD: Pharmacotherapies in adults

Serotonin reuptake inhibitor (SRI) medications are well established as first-line pharmacotherapeutic treatment for Obsessive-Compulsive Disorder (OCD). However, despite the excellent safety profile and demonstrated ef-ficacy of these medications, a substantial proportion of individuals with OCD fail to attain sufficient benefit from SRIs. In this narrative review, we discuss clinical features of OCD that have been associated with poorer response to SRIs, and we present pharmacotherapeutic interventions that have been explored as augmenting or alternative treatments for treatment-resistant OCD. We additionally highlight non-SRI interventions for OCD that are currently under investigation. Pharmacotherapeutic interventions were identified via expert consensus. To assess the evidence base for in-dividual pharmacotherapies, targeted searches for relevant English-language publications were performed on standard biomedical research databases, including MEDLINE. Information relevant to ongoing registered clinical trials in OCD was obtained by search of ClinicalTrials.gov. Pharmacotherapies are grouped for review in accordance with the general principles of Neuroscience-based Nomenclature (NbN). Clinical features of OCD that may suggest poorer response to SRI treatment include early age of onset, severity of illness, duration of untreated illness, and the presence of symmetry/ordering or hoarding-related symptoms. Based on evolving pathophysiologic models of OCD, diverse agents engaging serotonin, dopamine, norepi-nephrine, glutamate, and anti-inflammatory pathways have been explored as alternative or adjunctive therapies for treatment-resistant OCD and have at least preliminary evidence of efficacy. Medications with dopamine antagonist activity remain the most robustly evidence-based of augmenting in-terventions, yet dopamine antagonists benefit only a minority of those who try them and carry elevated risks of adverse effects. Interventions targeting glutamatergic and anti-inflammatory pathways are less well evidenced, but may offer more favorable benefit to risk profiles. Ongoing research should explore whether specific in-terventions may benefit individuals with particular features of treatment-resistant OCD

Lifetime Bipolar Disorder comorbidity and related clinical characteristics in patients with primary Obsessive Compulsive Disorder: a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS)

IntroductionBipolar disorder (BD) and obsessive compulsive disorder (OCD) are prevalent, comorbid, and disabling conditions, often characterized by early onset and chronic course. When comorbid, OCD and BD can determine a more pernicious course of illness, posing therapeutic challenges for clinicians. Available reports on prevalence and clinical characteristics of comorbidity between BD and OCD showed mixed results, likely depending on the primary diagnosis of analyzed samples.MethodsWe assessed prevalence and clinical characteristics of BD comorbidity in a large international sample of patients with primary OCD (n = 401), through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) snapshot database, by comparing OCD subjects with vs without BD comorbidity.ResultsAmong primary OCD patients, 6.2% showed comorbidity with BD. OCD patients with vs without BD comorbidity more frequently had a previous hospitalization (p < 0.001) and current augmentation therapies (p < 0.001). They also showed greater severity of OCD (p < 0.001), as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).ConclusionThese findings from a large international sample indicate that approximately 1 out of 16 patients with primary OCD may additionally have BD comorbidity along with other specific clinical characteristics, including more frequent previous hospitalizations, more complex therapeutic regimens, and a greater severity of OCD. Prospective international studies are needed to confirm our findings.Peer reviewe

Early intervention for obsessive compulsive disorder : An expert consensus statement

© 2019 Elsevier B.V.and ECNP. All rights reserved.Obsessive-compulsive disorder (OCD) is common, emerges early in life and tends to run a chronic, impairing course. Despite the availability of effective treatments, the duration of untreated illness (DUI) is high (up to around 10 years in adults) and is associated with considerable suffering for the individual and their families. This consensus statement represents the views of an international group of expert clinicians, including child and adult psychiatrists, psychologists and neuroscientists, working both in high and low and middle income countries, as well as those with the experience of living with OCD. The statement draws together evidence from epidemiological, clinical, health economic and brain imaging studies documenting the negative impact associated with treatment delay on clinical outcomes, and supporting the importance of early clinical intervention. It draws parallels between OCD and other disorders for which early intervention is recognized as beneficial, such as psychotic disorders and impulsive-compulsive disorders associated with problematic usage of the Internet, for which early intervention may prevent the development of later addictive disorders. It also generates new heuristics for exploring the brain-based mechanisms moderating the ‘toxic’ effect of an extended DUI in OCD. The statement concludes that there is a global unmet need for early intervention services for OC related disorders to reduce the unnecessary suffering and costly disability associated with under-treatment. New clinical staging models for OCD that may be used to facilitate primary, secondary and tertiary prevention within this context are proposed.Peer reviewe

Manifesto for a European research network into Problematic Usage of the Internet

Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.The Internet is now all-pervasive across much of the globe. While it has positive uses (e.g. prompt access to information, rapid news dissemination), many individuals develop Problematic Use of the Internet (PUI), an umbrella term incorporating a range of repetitive impairing behaviours. The Internet can act as a conduit for, and may contribute to, functionally impairing behaviours including excessive and compulsive video gaming, compulsive sexual behaviour, buying, gambling, streaming or social networks use. There is growing public and National health authority concern about the health and societal costs of PUI across the lifespan. Gaming Disorder is being considered for inclusion as a mental disorder in diagnostic classification systems, and was listed in the ICD-11 version released for consideration by Member States (http://www.who.int/classifications/icd/revision/timeline/en/). More research is needed into disorder definitions, validation of clinical tools, prevalence, clinical parameters, brain-based biology, socio-health-economic impact, and empirically validated intervention and policy approaches. Potential cultural differences in the magnitudes and natures of types and patterns of PUI need to be better understood, to inform optimal health policy and service development. To this end, the EU under Horizon 2020 has launched a new four-year European Cooperation in Science and Technology (COST) Action Programme (CA 16207), bringing together scientists and clinicians from across the fields of impulsive, compulsive, and addictive disorders, to advance networked interdisciplinary research into PUI across Europe and beyond, ultimately seeking to inform regulatory policies and clinical practice. This paper describes nine critical and achievable research priorities identified by the Network, needed in order to advance understanding of PUI, with a view towards identifying vulnerable individuals for early intervention. The network shall enable collaborative research networks, shared multinational databases, multicentre studies and joint publications.Peer reviewe

Proportionate methods for evaluating a simple digital mental health tool

Background: Traditional evaluation methods are not keeping pace with rapid developments in mobile health. More flexible methodologies are needed to evaluate mHealth technologies, particularly simple, self-help tools. One approach is to combine a variety of methods and data to build a comprehensive picture of how a technology is used and its impact on users. Objective: This paper aims to demonstrate how analytical data and user feedback can be triangulated to provide a proportionate and practical approach to the evaluation of a mental wellbeing smartphone app (‘In Hand’). Methods: A three-part process was used to collect data: 1) app analytics; 2) an online user survey; and 3) interviews with users. Findings: Analytics showed that >50% of user sessions counted as ‘meaningful engagement’. User survey findings (N=108) revealed that In Hand was perceived to be helpful on several dimensions of mental wellbeing. Interviews (N=8) provided insight into how these self-reported positive effects were understood by users. Conclusions: This evaluation demonstrates how different methods can be combined to complete a real-world, naturalistic evaluation of a self-help digital tool and provide insights into how and why an app is used and its impact upon users’ wellbeing. Clinical implications: This triangulation approach to evaluation provides insight into how wellbeing apps are used and their perceived impact on users’ mental wellbeing. This approach is useful for mental healthcare professionals and commissioners who wish to recommend simple digital tools to their patients and evaluate their uptake, use and benefits

Serotonin tranporter methylation and response to cognitive behaviour therapy in children with anxiety disorders

Anxiety disorders that are the most commonly occurring psychiatric disorders in childhood, are associated with a range of social and educational impairments and often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for the majority of cases, although up to 35-45% of children do not achieve remission. Recent research suggests that some genetic variants may be associated with a more beneficial response to psychological therapy. Epigenetic mechanisms such as DNA methylation work at the interface between genetic and environmental influences. Furthermore, epigenetic alterations at the serotonin transporter (SERT) promoter region have been associated with environmental influences such as stressful life experiences. In this study, we measured DNA methylation upstream of SERT in 116 children with an anxiety disorder, before and after receiving CBT. Change during treatment in percentage DNA methylation was significantly different in treatment responders vs nonresponders. This effect was driven by one CpG site in particular, at which responders increased in methylation, whereas nonresponders showed a decrease in DNA methylation. This is the first study to demonstrate differences in SERT methylation change in association with response to a purely psychological therapy. These findings confirm that biological changes occur alongside changes in symptomatology following a psychological therapy such as CBT

Learning to Deal with Problematic Usage of the Internet

An easily accessible guide for patients, caregivers, family members, and health care professionals presenting a state of the art overview of Problematic Use of the Internet. Ever since its development in the early 1990’s, the Internet has become highly pervasive across most of the civilised world. While the majority of Internet users take advantage of its many positive uses (including professional and recreational ones), some individuals can develop Problematic Use of the Internet (which we will refer to as PUI). This term encompasses a wide range of repetitive disabling behaviors characterized by compulsivity and addiction. These include, but are not limited to, Internet gaming, compulsive online sexual behaviors/ cyberpornography, Internet-related buying or shopping disorder, Internet-related gambling disorder, cyberbullying, cyberchondria, and social media/network forum use, among others. Although PUI affects a minority of individuals who routinely use the Internet, several reports have documented a series of unhealthy lifestyles and medical disturbances which are thought to represent the consequences of severe forms of PUI, especially when it comes to youth. People affected by PUI and their family members often do not know about the signs and symptoms of this condition. For example, they do not know how to recognize PUI, or whom to go to for help, and often they do not know whether this is a treatable condition and/or how to manage it. Because of this, National Health Authorities around the World are concerned about the health and societal costs that PUI may have. Some researchers are starting to consider particular forms of PUI as a serious and disabling form of behavioral addiction. We developed this companion book in an attempt to provide an easily accessible guide for the public, patients, caregivers, family members, and health care professionals presenting a state of the art overview of PUI. This initiative stems from the work of an international panel of experts participating in a 4-year COST Action project “European Network for Problematic Usage of the Internet” CA16207, funded by the Horizon 2020 Framework Programme of the European Union, which began in October 2017 and whose Principle Investigator, Prof. Naomi Fineberg, aimed to bring a multidisciplinary and geographically diverse group of experts and opinion leaders together under one European-led network to: advance the understanding of PUI from a bio-psycho-social perspective, to clarify brain-based causal mechanisms, and to develop effective interventions for the various forms of disorder

Placebo response in trichotillomania

Background: Trichotillomania is a functionally impairing, often overlooked disorder with no FDA-approved medications indicated for its treatment. The ability of clinical trials to detect beneficial effects of pharmacologic treatment in trichotillomania has been hampered by the high placebo response rate. Very little is known about baseline demographic and clinical characteristics that may be predictive of placebo response in such patients. Methods: 104 participants assigned to placebo were pooled from five double-blind trials conducted at three sites in the United States and Canada. Participants were classified as placebo responders or non-responders based on a cut-off of 35% reduction in symptom severity on the Massachusetts General Hospital Hair Pulling Scale (MGH-HPS). Baseline group differences were characterized using t-tests and equivalent non-parametric tests as appropriate. Results: Thirty-one percent of individuals assigned to placebo treatment showed a significant clinical response to placebo. Placebo responders (n=32) and non-responders (n=72) did not differ significantly on any demographic or clinical variable. Discussion: Predictors of placebo response for trichotillomania remain elusive and do not appear similar to those reported for other mental health disorders.Dr. Grant has received research grant support from TLC Foundation for BFRBs, NIDA, NIAAA, National Center for Responsible Gaming, Brainsway, Psyadon and Takeda Pharmaceuticals. Dr. Chamberlain’s involvement in this project was funded by a Wellcome Trust Clinical Fellowship (110049/Z/15/Z). Dr. Odlaug has received research funding from the TLC Foundation for BFRBs. Dr Keuthen has received research support from the TLC Foundation for BFRBs and Forest Laboratories