J. Zohar

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision

In this report, which is an update of a guideline published in 2002 (Bandelow et al. 2002, World J Biol Psychiatry 3:171), recommendations for the pharmacological treatment of anxiety disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are presented. Since the publication of the first version of this guideline, a substantial number of new randomized controlled studies of anxiolytics have been published. In particular, more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs. The recommendations, developed by the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-traumatic Stress Disorders, a consensus panel of 30 international experts, are now based on 510 published randomized, placebo- or comparator-controlled clinical studies (RCTs) and 130 open studies and case reports. First-line treatments for these disorders are selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and the calcium channel modulator pregabalin. Tricyclic antidepressants (TCAs) are equally effective for some disorders, but many are less well tolerated than the SSRIs/SNRIs. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of substance abuse disorders. Potential treatment options for patients unresponsive to standard treatments are described in this overview. Although these guidelines focus on medications, non-pharmacological were also considered. Cognitive behavioural therapy (CBT) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders, OCD, and PTSD to support them being recommended either alone or in combination with the above medicines.

Obsessive Compulsive Disorder: Serotonin and Beyond

Summary: OCD was considered a rare, treatment refractory disorder of psychological origin, up until 20 years ago. Research in the last two decades has altered the perspectives regarding OCD. It is now clear that OCD is a prevalent disorder—about 2% of the population suffer from OCD—and that it is amenable both to psychological (cognitive-behavioural approach) and pharmacological intervention (with serotonergic medication). The biochemical and neuroanatomical (the frontal basal-thalamo cortical circuit) pathophysiology of OCD is also beginning to emerge. OCD is unique with regards to its specific response to serotonergic medication that blocks reuptake. Clomiprimine, fluoxetine, fluvoxemine, paroxetine, sertraline and citalopram were all found to be effective treatments for OCD based on large, multicentre, double-blind, placebo-controlled studies. As only serotonergic medications appear to be effective in OCD, the serotonergic hypothesis has been formulated and tested. Indeed, pharmacological challenges with specific serotonin agonists such as mCPP and sumatriptan, which were associated with transient exacerbation of OCD symptoms, are in line with the specific role of 5HT in the pathogenesis of OCD. However, this serotonergic hypothesis, while necessary, is not sufficient. It is clear that the dopaminergic and autoimmune mechanism are also implicated in the pathogenesis of OCD. Further studies are required to understand the relevance of the serotonergic and non-serotonergic systems in OCD, and to highlight the various possible subtypes of this intriguing disorder.

Physical co-morbidity among treatment resistant vs. treatment responsive patients with major depressive disorder

Co-morbid physical illness has been suggested to play an important role among the factors contributing to treatment resistance in patients with major depressive disorder. In the current study we compared the rate of physical co-morbidity, defined by ICD-10, among a large multicenter sample of 702 patients with major depressive disorder. A total of 356 of the participants were defined as treatment resistant depression (TRD) patients-having failed two or more adequate antidepressant trials. No significant difference was found between TRD and non-TRD participants in the prevalence of any ICD-10 category. This finding suggests that although physical conditions such as diabetes, thyroid dysfunction, hypertension, ischemic heart disease, and peptic diseases are often accompanied by co-morbid MDD, they do not necessarily have an impact on the course of MDD or the likelihood to respond to treatment. Marginally higher rates of co-morbid breast cancer, migraine and glaucoma were found among TRD participants. Possible explanations for these findings and their possible relation to TRD are discussed.

Obsessive-compulsive disorder in the elderly: A report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS)

INTRODUCTION Obsessive-compulsive disorder (OCD) is a highly disabling condition, with frequent early onset. Adult/adolescent OCD has been extensively investigated, but little is known about prevalence and clinical characterization of geriatric patients with OCD (G-OCD≥65years). The present study aimed to assess prevalence of G-OCD and associated socio-demographic and clinical correlates in a large international sample. METHODS Data from 416 outpatients, participating in the ICOCS network, were assessed and categorized into 2 groups, age<vs≥65years, and then divided on the basis of the median age of the sample (age<vs≥42years). Socio-demographic and clinical variables were compared between groups (Pearson Chi-squared and t tests). RESULTS G-OCD compared with younger patients represented a significant minority of the sample (6% vs 94%, P<.001), showing a significantly later age at onset (29.4±15.1 vs 18.7±9.2years, P<.001), a more frequent adult onset (75% vs 41.1%, P<.001) and a less frequent use of cognitive-behavioural therapy (CBT) (20.8% vs 41.8%, P<.05). Female gender was more represented in G-OCD patients, though not at a statistically significant level (75% vs 56.4%, P=.07). When the whole sample was divided on the basis of the median age, previous results were confirmed for older patients, including a significantly higher presence of women (52.1% vs 63.1%, P<.05). CONCLUSIONS G-OCD compared with younger patients represented a small minority of the sample and showed later age at onset, more frequent adult onset and lower CBT use. Age at onset may influence course and overall management of OCD, with additional investigation needed.

A comparison between print vs. internet methods for a clinical trial recruitment—A pan European OCD study

Recruitment for clinical studies presents a serious challenge in terms of meeting both time and budget constraints. The internet offers a potentially powerful means for quick and effective recruitment-either as an add-on or as alternative to traditional methods. We developed a Google search based solution which enhances patient recruitment. Recruitment via internet was associated with greater exposure to relevant applicants and better response to treatment as compared to traditional printed ads.

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

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.

Clinical factors predicting treatment resistant depression: affirmative results from the European multicenter study

Clinical variables were investigated in the ‘treatment resistant depression (TRD)‐ III’ sample to replicate earlier findings by the European research consortium ‘Group for the Study of Resistant Depression’ (GSRD) and enable cross‐sample prediction of treatment outcome in TRD.

P.2.b.035 The combined effect of genetic polymorphisms and clinical parameters on treatment response and resistance in major depressive disorder

BDNF and PDYN (p< 0.05, Spearman r = 0.2017) and an inverse correlation with two PDYN SNPs (rs1997794 and rs2281285). Conclusions: Our results are consistent with the epigenetic theory of psychosis, supporting the importance of alterations of epigenetic mechanisms in the etiology of BD and MDD. They also provide a new and clear correlation between changes in the epigenetic level of the BDNF and PDYN gene, suggesting their interaction in the development of BD. We also confirm that the use of PBMCs could be exploited as a reliable model of the complex epigenetic mechanisms leading to the discovery of biomarkers of diseases. Finally, we further suggest the relevance of integrating data on genetic variants and DNA methylation.

P.2.b.026 Social adjustment among therapy responder patients with mood disorders

A. Chiesa1 °, A. Serretti1, D. Souery2, R. Calati1, O. Sentissi3, S. Kasper4, E. Akimova4, J. Zohar5, D. Amital6, S. Montgomery7 1Department of Biomedical and Neuromotor Science, University of Bologna, Bologna, Italy; 2Laboratoire de Psychologie Medicale, Universite Libre de Bruxelles and Psy Pluriel Centre Europeen de Psychologie Medicale, Brussels, Belgium; 3Departement de Psychiatrie Hopitaux Universitaires de Geneve, Faculte de Medecine de Geneve, Geneve, Switzerland; 4Department of Psychiatry and Psychotherapy, Medical University, Vienna, Austria; 5Chaim Sheba Medical Center, Chaim Sheba Medical Center, Tel-Hashomer, Israel; 6Imperial College School of Medicine, Imperial College School of Medicine, London, United Kingdom; 7Laboratoire de Psychologie Medicale, Universite Libre de Bruxelles, Brussels, Belgium

P.3.026 Clinical and genetic predictors of antidepressant response and remission in treatment-resistant depression

R. Calati1 °, I. Massat2, S. Kasper3, S. Montgomery4, J. Zohar5, J. Mendlewicz6, A. Serretti1. 1University of Bologna, Institute of Psychiatry, Bologna, Italy; 2Université Libre de Bruxelles, Fonds de la Recherche Scientifique (FNRS) Laboratoire de Neurologie Expérimentale, Brussels, Belgium; 3Medical University Vienna, Department of Psychiatry and Psychotherapy, Vienna, Austria; 4University of London, Imperial College, London, United Kingdom; 5Chaim Sheba Medical Center, Chaim Sheba Medical Center, Tel-Hashomer, Israel; 6Université Libre de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium