Replicated evidence indicates that bipolar disorder is associated with alterations in molecular, cellular, and neuro systems that involve disparate metabolic and inflammatory pathways. Conventional treatments for bipolar disorder have largely been identified serendipitously rather than based on an a priori disease model. Consensus exists that available treatments for bipolar disorder are neither disease modifying nor targeting critical effector systems implicated in this disorder. This presentation will provide a rationale for exploring drug development opportunities for critical metabolic systems including glucagon-like-peptide and insulin systems as well as critical inflammatory pathways. Novel proof of concept data will be presented for several novel pharmacological approaches, e.g. insulin, minocycline, and infliximab.

In bipolar disorder (BD), illness progression has been associated with a higher number of mood episodes and hospitalizations, reduced interepisode intervals, poorer response to treatment, and cognitive/functional impairment. The term ‘neuroprogression” has been proposed to describe the pathological rewiring of the brain that takes place when clinical and cognitive deterioration occurs in the context of the progression of BD. Accordingly, neuroprogression would correspond to the biological underpinnings of illness progression and staging in BD. In some cases of BD it is possible to identify an active process of neuroprogression mediated by immune activation which cincludes: a) inflammation, b) changes in growth factors, c) oxidative stress and d) mitochondrial dysfunction. Recent evidence showing neuroinflammation in BD suggest that it may be associated with neuroprogressive changes such as incremental volume loss in brain, cognitive changes, and a declining likelihood of response to pharmacological and psychosocial treatments. Prompt treatment may be potentially neuroprotective and attenuate the volumetric and neurocognitive changes that emerge with chronicity. Accumulating evidence suggest that the assessment of immune activation in BD may be a means to assess illness progression. Interventions aiming at reducing immune activation in BD are currently being tested.

Beyond symptom remission, recovery aims at inclusion and social participation of psychiatric patients irrespective of remaining symptoms and disabilities. It thus places a focus on the patients’ individual resources and creativity, which enable them to participate in society. It also places a strong focus on social exclusion and stigmatization, may they result from passive avoidance or active exclusion of subjects with mental disorders. As such, fighting stigma includes a reflection on the role of psychiatry as a health care institution and its everyday practices. We discuss a person-centred approach in psychiatry that aims at inclusion in the life world and community and discuss several steps that facilitate recovery: reduction of coercive treatment by opening the doors of acute wards, rehabilitation via job placement, empowerment in advocacy groups as well as in the supervision of public health policy, hospital settings and treatment, and direct participation of experienced uses in therapeutic teams. With increasing globalization, we also emphasize the necessary intercultural openness of mental health care institutions and the participation of migrants both in devising health care settings as well in therapeutic teams.

The goal of an human-based or human oriented Psychiatry must be that the therapist does not only just superficially register symptoms of disease with a view to creating the basis for a subsequent attempt at ‘symptom-killing”, or making illness constructs disappear, but to work together with the patient to find new ways that will enable the patient to find a way out of his suffering and to return to a life he has chosen for himself that is as autonomous and happy as possible. The return to a life that is as autonomous and happy as possible as an expression of the comprehensive state of well-being defined by the WHO is also the most important treatment goal of human-based medicine. To achieve it, we have to move beyond a simple deficiency orientation to develop a resource-oriented treatment programme of the kind that was recently presented in the form of the Anton Proksch Institute’s Orpheus Programme, a modular therapy programme for addicts that is based on attractive treatment objectives and a life that holds joy. Besides the usual physical, psychological, social and spiritual resources, the main resources that are to be used in this treatment programme are those of Beauty and those of the possible.

Nowadays, there is an unprecedented degree of interconnectivity and mobility, that makes worthwhile to look for migration onto the new global context by recognizing the push factors that pressure people to leave the donor country, the pull factors that make the recipient country seem attractive, confirming patterns and duration of flows.

Due to the scarcity of data, in order to explore migration among psychiatry trainees, the European Federation of Psychiatry Trainees (EFPT) has done a survey to assess opinions and experiences of international migration. The results provided by this study bring an overview of migration among trainees and the challenges faced in this pathway. This data analysis and discussion can lead to further comparisons with other groups, contributing to the necessary steps into effective policy interventions that optimize the impact of migration for all the concerned.

Since Brain Drain has moved to the forefront agendas, as an attempt to guide national action and multilateral cooperation, WHO reported in its Global Code of Practice on International Recruitment of Health Personnel a framework for tackling the shortage in the global health workforce, with ethical, legal and institutional considerations. However, greater efforts are still needed to ensure that health workforce systems are strengthened everywhere.

These individuals that migrate have to adjust to new surroundings and to cope with the stresses, which is potential for the disruption of their mental health. Migration within psychiatry will probably continue, being essential to enhance support to those who migrate, and actually influence the mental health care provided internationally.

Workforce migration of health professionals is influencing countries’ health services. In this new global context it is worthwhile to look for actual and future migration by recognizing the push factors that pressure people to leave the donor country, the pull factors that make the recipient country seem attractive, while confirming patterns and duration of migration.

Despite the concern for migration has moved to the forefront agendas raising questions, there is lack of data of migration flows, as significant highly skilled migration has been within the European Union, and additionally, there is scarcity of data in psychiatry.

As an attempt to explore migration among psychiatry trainees, the European Federation of Psychiatry Trainees (EFPT) has done a cross-sectional European multicentre study, collecting data from 2281 psychiatric trainees across 33 countries, assessing opinions and experiences of international migration.

The results provided by this study bring an overview of migration among psychiatric trainees. This data analysis and discussion will permit further comparisons with other groups, such as physicians in general and psychiatry consultants worldwide.

The possibility to endorse discussion in this symposium addressing the starting period of the training, having an outline of migration and the different cultural challenges faced on the way to a psychiatry career, may raise awareness on the current trends, help to elucidate the underlying issues and recommend possible systems of support.

Migration within psychiatry will probably continue, being therefore essential to enhance support to those who migrate, and actually influence the mental health care provided internationally.

Ways of travelling and means of communication have exponentially developed, while their price has dropped. It is now relatively easy for a psychiatrist to travel in different countries in the early stages of his career. The development of European programs such as Erasmus has increased exchanges during medical school. After graduation, it is possible to travel abroad for a few weeks as an observer, months a researcher, but also for one’s entire life, as European legislation has made it possible for doctors to register and permanently work in many countries. The crisis in recruitment of psychiatrists that many countries face has put junior doctors in a position of finding a job almost wherever they want.

On the one hand, this phenomenon tends to drain resources in less favoured countries, and psychiatrists travelling the world might become mercenaries, looking for the best opportunities and not being able to maintain consistency in service provision. This would ultimately lead to psychiatrists only becoming technicians, providing a service for a fixed period of time, and being replaced as leaders by managers in charge of running services.

On the other hand, this constitutes a unique chance from a personal point of view, as a way to gain experience and discover other cultures. From a professional point of view, working in a different system is also a valuable experience, and the travelling doctor can bring his own culture and tend to naturally ‘think outside the box”, benefiting the service and the patients. In addition, a growing number of patients migrating themselves and coming from diverse backgrounds will benefit from a psychiatrist with a personal experience of migration.

The mental health workforce is a precious resource for countries. A high level of inverstment has been committed to train doctors, psychologists and nurses. Most European countries also suffer from a relative shortage of trained staff. The migration of such professionals is therefore a major loss of skills, and also exacerbates existing shortages in many countries.

Within the EU, staff migration is a fundamental right that cannot be challenged. Staff migration has a number of undesirable consequences, both to countries of origin and receiving countries that lead to actions. Migration leads to wage increases in order to tempt people to stay. This is in the interest of the individuals targeted, but affects other health service priorities since overal health service budgets are rarely adjusted.

The WHO European Mental Health Action Plan (EMHAP) draws attention to the challenges of migration. The diversity of clinical practice in Europe is still reflected in the diversity of curricula. Considering the extent of professional migration across the Region, reliable competencies need to be assured. Interventions for mental health problems need to be guided by professional codes of practice, as well as adherence to legal standards across the Region. This will require partnership between profesional bodies, governments and intergovernmental organizations. The endorsement of the EMHAP is a mandate for Action in this field, aiming to find a balance between rights of the individuals to work where they choose and offering protection for the wellbeing of the population.

Hemocue leuco+diff and DBS are two recent technological advances that can beneficially affect clozapine treatment in the near future.

1. 1. Hemocue Leuco+diff is a new point of care instrument that provides both a total white blood cel count as that of the five most common types of leucytes (neutrophils, lymphocytes, monocytes, eosinophils and basophils). In an open study in 70 patients on clozapine maintenance treatment, 39 clinical and 31 out-patients, the tolerability and the (dis-), advantages of the two methods of blood sampling, venous versus point-of care, were compared. In four consecutive monthly measurements, the method of blood sampling alternated monthly from point-of-care to venous and the other way around, from venous sampling to point-of-care. In those patients who indicated a preference, point of care method was preferred because it is less burdensome (no travelling involved, no waiting time) and immediate access to the results.

2. 2. The dried blood spot (DBS) is a method of measurement of drug plasma levels in a drop of dried blood on standardized paper card. DBS has been validated for antibiotic therapy of fungal infections and the treatment of tuberculosis. In a study of 15 outpatients on clozapine maintenance therapy we studied the non-inferiority of clozapine monitoring with DBS compared with venous blood sampling. We will present the first results and the possible implications of the outcome for clinical practice.

Treatment resistant schizophrenia (TRS) is one of the most disabling of psychiatric disorders, affecting about 1/3 of patients. First-line treatments include both atypical and typical antipsychotics. The original atypical, clozapine, is a final option, and although it has been shown to be the only effective treatment for TRS, many patients do not respond well to clozapine. Clozapine use is related to adverse events, most notably agranulocytosis, a potentially fatal blood disorder which affects about 1% of those prescribed clozapine and requires regular blood monitoring. This as a barrier to prescription and there is a long delay in access for TRS patients, of five or more years, from first antipsychotic prescription. Better tools to predict treatment resistance and to identify risk of adverse events would allow faster and safer access to clozapine for patients who are likely to benefit from it. The CRESTAR project (www.crestar-project.eu) is a European Framework 7 collaborative project that aims to develop tools to predict i) treatment response, particularly patients who are less likely to respond to usual antipsychotics, indicating treatment with clozapine as early as possible, ii) patients who are at high or low risk of adverse events and side effects, iii) extreme TRS patients so that they can be stratified in clinical trials for novel treatments. CRESTAR has addressed these questions by examining genome-wide association data, genome sequence, epigenetic biomarkers and epidemiological data in European patient cohorts characterized for treatment response, and adverse drug reaction using data from clozapine therapeutic drug monitoring and linked National population medical and pharmacy databases, to identify predictive factors. In parallel CRESTAR will perform health economic research on potential benefits, and ethics and patient-centred research with stakeholders.

What do carers of schizophrenia patients need during first contact with psychiatric services?

Employment and unemployment have becomemajor topics in mental health care and also in the public discussion. Employment is no longer considered the mere goal of psychiatric rehabilitationbut serves as a rehabilitative measure itself. Supported Employment (SE)according to the principle IndividualPlacement and Support (IPS) has made its way from the United States toEurope in the last decade. The EQOLISE-Trial (Burns et. al. 2007) can be considered theproof of principle of IPS in Europe. Not only had the main outcomecriterion, i.e.employment on the open Job market, successfully been reached. Moreover, it was shown that IPS influences psychopathology, rehospitalisationsand days spent in Hospital in a positive manner. Since then, more randomized controlled trials(RCTs) such as the Placement-Budgets-Trial (ISRCTN89670872), the ZHEPP-trial(ISRCTN54951166) and SE plus (ISRCTN02422335) have been initiated. These RCTscomprise a total of about 500 participants and focus on factors such as thetime needed to find a job, the applicability of IPS on job maintenance and on thepossibility to find a job for persons who receive disability pensions. Secondary outcome criteria are, among others, clinical and social functioning, motivation, and stigma. Data from these trials, from retrospective clinical analysesand from an EQOLISE follow-up at the Zurich site will be presented.

Evaluating innovative mental health care in Germany

Thomas Becker, Annabel Stierlin, Reinhold Kilian, Ulm/Günzburg, Germany

There is an interest in innovative mental health service models in Germany. This comprises, among others, crisis intervention and home treatment service models and assertive community treatment teams. Innovative funding models are being put to test. There are several catchment areas in the country where care is provided according to a capitation funding model that gives a high degree of freedom to health care providers in what services they use to provide care for patients (Regionale Psychiatriebudgets). Models of this type are also used in so-called model projects on the basis of federal law (Modellvorhaben §64b SGBV). In Hamburg, a comprehensive community- and hospital-based service for people with severe mental illness has been implemented (IV Vertrag) and put to test in the ACCESS trial. The focus of this talk is on an observational controlled trial (IVPower) studying the effectiveness and cost-effectiveness of an integrated community-base care programme (NWpG) implemented in several regions of Germany (in five federal states, Schleswig-Holstein, Northrhine-Westfalia, Berlin, Saxony and Bavaria. The 18-month multi-centre observational trial enrolls 250 patients in the NWpG programme and 250 patients who receive treatment as usual from routine mental health services in five catchment areas. Data are collected at baseline and three follow-ups after 6, 12 and 18 months Preliminary study results will be presented and discussed.

Fight against depression and suicide in Europe: evidence-based tools partly utilised.

Results of JA situation analysis

György Purebl, Tamás Kurimay

Semmelweis University of Medicine, Budapest, Hungary

Research is quite limited in terms of production of evidence regarding psychosocial interventions or pharmacological treatments for suicidal risk. Such evidence is poor also because suicidal patients were systematically excluded from clinical trials, for ethical reasons. Several key ideas are important in the management of the suicidal person. First, the multidimensional assessment of suicidal risk defines the areas of interference with various axis I or axis II disorders, but also with the complex psychosocial environment of such patients. The therapeutic approach must be adapted by taking into account various factors (i.e. gender, age group, degree of social exclusion, etc.). Furthermore, case management must take into account the type of suicidal behavior (acute suicidal crisis or chronic suicidal state), this typology being dependent on the link with axis I disorders, more frequent in acute suicidal crisis, or with disorders belonging axis II, more common in chronic, repetitive suicidal behavior.

Pharmacological prevention of suicide in patients with mood disorder

Zoltán Rihmer

Semmelweis University

National Institute of Psychiatry and Addictions

In spite of the fact that around two-thirds of suicide victims have current major depressive episode, and up-to half of them contact different levels of health-care services during the last 4 weeks of their life, over 80% of depressed suicides are untreated or inadequately treated.

However, several large-scale, naturalistic, observational follow-up studies show that successful acute and long-term treatment of major depression (with antidepressants) and bipolar disorders (with mood stabilizers, antidepressants and/or antipsychotics) markedly reduces the risk of further suicide attempts and committed suicide. Suicidal behaviour in unipolar depressives taking antidepressants is relatively most frequent among nonresponders and in the first 10-14 days of the treatment, several days before the start of action of the drug. Register based cohort studies also found that continuous treatment with antidepressants or mood stabilizers substantially reduced the risk of subsequent suicidal behaviour in unipolar or bipolar patients compared to those who were not pharmacologically treated. The marked decline of national suicide rates in countries where antidepressant utilization increased by three-to-eightfold recently also supports the antisuicidal effect of antidepressants, even on the level of general population. As anxiety, insomnia and psychotic features markedly increase the suicide risk among depressives, supplementary medication with anxiolytics in the case of insommnia or comorbid anxiety and with atypical antipsychotics in patients with psychotic depression is also necessary at least for short-time. However, psychosocial interventions, including psycho-education are allways needed.