Zonisamide augmentation in poor- or non-responder patients treated with duloxetine for a major depressive episode

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sychiatry

OFFICIAL JOURNAL OF THE WORLD PSYCHIATRIC ASSOCIATION (WPA)

Volume 8, Supplement 1

February 2009

WORLD PSYCHIATRIC ASSOCIATION

INTERNATIONAL CONGRESS

“TREATMENTS IN PSYCHIATRY: A NEW UPDATE”

April 1-4, 2009

Florence, Italy

ABSTRACTS

000-000_Copertina_WB-xp6.qxd 6-03-2009 15:29 Pagina IV

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Printed in Italy by Legoprint SpA, via Galilei, 11 - 38015 Lavis, TN

The World Psychiatric Association (WPA)

The WPA is an association of national psychiatric societies aimed to increase knowledge and skills necessary for work in the field of mental health and the care for the mentally ill. Its member societies are presently 134, spanning 122 different countries and representing more than 200,000 psychiatrists.

The WPA organi zes the World Congress of Psychiatry every three years. It also organizes international and regional congresses and meetings, and thematic conferences. It has 65 scientific sections, aimed to disseminate information and pro-mote collaborative work in specific domains of psychiatry. It has produced several educational programmes and series of books. It has developed ethical guidelines for psychiatric practice, including the Madrid Declaration (1996).

Further information on the WPA can be found on the web-site www.wpanet.org.

WPA Executive Committee

President – M. Maj (Italy) President-Elect – P. Ruiz (USA) Secretary General – L. Küey (Turkey) Secretary for Finances – T. Akiyama (Japan) Secretary for Meetings – T. Okasha (Egypt) Secretary for Education – A. Tasman (USA) Secretary for Publications – H. Herrman (Australia) Secretary for Sections – M. Jorge (Brazil)

WPA Secretariat

Psychiatric Hospital, 2 Ch. du Petit-Bel-Air, 1225 Chêne-Bourg, Geneva, Switzerland. Phone: +41223055736; Fax: +41223055735; E-mail: wpasecretariat@wpanet.org.

World Psychiatry

World Psychiatry is the official journal of the World Psychiatric Association. It is published in three issues per year and is sent free of charge to psychiatrists whose names and addresses are provided by WPA member societies and sec-tions.

Research Reports containing unpublished data are wel-come for submission to the journal. They should be subdivid-ed into four sections (Introduction, Methods, Results, Discussion). References should be numbered consecutively in the text and listed at the end according to the following style: 1. Bathe KJ, Wilson EL. Solution methods for eigenvalue

problems in structural mechanics. Int J Num Math Engng 1973;6:213-26.

2. McRae TW. The impact of computers on accounting. London: Wiley, 1964.

3. Fraeijs de Veubeke B. Displacement and equilibrium models in the finite element method. In: Zienkiewicz OC, Hollister GS (eds). Stress analysis. London: Wiley, 1965:145-97. All submissions should be sent to the office of the Editor.

Editor – M. Maj (Italy).

Associate Editor – H. Herrman (Australia).

Editorial Board – P. Ruiz (USA), L. Küey (Turkey), T. Akiyama

(Japan), T. Okasha (Egypt), A. Tasman (USA), M. Jorge (Brazil).

Advisory Board – H.S. Akiskal (USA), R.D. Alarcón (USA), S.

Bloch (Australia), G. Christodoulou (Greece), J. Cox (UK), H. Freeman (UK), M. Kastrup (Denmark), H. Katschnig (Austria), D. Lipsitt (USA), F. Lolas (Chile), J.J. López-Ibor (Spain), J.E. Mezzich (USA), R. Montenegro (Argentina), D. Moussaoui (Morocco), P. Munk-Jorgensen (Denmark), F. Njenga (Kenya), A. Okasha (Egypt), J. Parnas (Denmark), V. Patel (India), N. Sartorius (Switzerland), B. Singh (Australia), P. Smolik (Czech Republic), R. Srinivasa Murthy (India), J. Talbott (USA), M. Tansella (Italy), S. Tyano (Israel), J. Zohar (Israel).

Office of the Editor – Department of Psychiatry, University of Naples SUN, Largo Madonna delle Grazie, 80138 Naples, Italy. Phone: +390815666502; Fax: +390815666523; E-mail: majmario@tin.it.

Managing Director & Legal Responsibility - Wubbo Tempel (Italy).

Published by Elsevier S.r.l., Via P. Paleocapa 7, 20121 Milan, Italy.

World Psychiatry is indexed in PubMed, Current Contents/Clinical Medicine, Current Contents/Social

and Behavioral Sciences, Science Citation Index, and EMBASE.

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WORLD PSYCHIATRIC ASSOCIATION

INTERNATIONAL CONGRESS

"TREATMENTS IN PSYCHIATRY:

A NEW UPDATE"

April 1-4, 2009

Florence, Italy

PRESIDENT OF THE CONGRESS

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ESI

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_{TOP-CITED SCIENTIST LECTURES}

TL1.

THE TREATMENT GAP IN PSYCHIATRY

R.C. Kessler

Department of Health Care Policy, Harvard Medical School, Boston, MA, USA

Data are presented on patterns, self-reported reasons for, and socio-demographic correlates of unmet need for treatment of mental disor-ders in 23 countries around the world. The data come from general population surveys carried out as part of the World Health Organiza-tion’s World Mental Health (WMH) Survey Initiative. Results show that a high proportion of people with DSM-IV mental disorders in all countries’ surveys fail to receive any form of professional treatment for their mental disorders. The data also show that many patients receive treatments that fail to meet even the most minimal acceptable standards of treatment quality. Unmet need for treatment is lower for more severely impairing than less severe cases, but is quite high even in more severe cases. Reason analysis shows that lack of perceived need, predisposing factors, and enabling factors all play separate roles in accounting for this treatment gap. Important insights into the causal processes that lead to associations between socio-demograph-ic sources of health care disparities and unmet need for treatment emerge by including these factors in the reason analysis.

TL2.

PSYCHIATRIC GENETICS: A CURRENT

PERSPECTIVE

K. Kendler

Virginia Institute of Psychiatric and Behavioral Genetics, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA, USA

This paper will first review the four major paradigms currently active in psychiatric genetics: simple genetic epidemiology, advanced genet-ic epidemiology, gene-finding methods and molecular genetgenet-ics. It will then review selectively advances in each of these areas, trying to illus-trate the methodological strengths and limitations of each approach. In the area of advanced genetic epidemiology, we will review exam-ples of genetic models of development, sex-modification of genetic effects, gene by environment interaction, and gene by environmental correlation. In the section on gene finding methods, we will review candidate gene association and linkage but focus on gene-wide asso-ciation methods. We will provide an up to the minute assessment of progress in this very rapidly moving area. We will also briefly touch on genomic approaches, especially copy number variants and the chal-lenges posed by allelic heterogeneity and the rare variant common disease model for psychiatric disorders.

TL3.

BIPOLARITY: A BROAD SPECTRUM (SPECTRA)

IN SEARCH OF TREATMENT

H.S. Akiskal

University of California at San Diego, La Jolla, CA, USA

“Bipolar spectrum” first appeared in the psychiatric literature in a 1977 paper on a prospective follow-up of cyclothymic individuals: most developed depression or bipolar II, fewer developed full blown

manic-depressive illness and, significantly, nearly half the sample treated with antidepressants developed increased cycling. Much of the evidence for this broadened bipolar concept has come during the past few years. Subthreshold bipolar conditions have been identified in the community and several epidemiological studies, in both Europe and the United States, showing an average population preva-lence of 5%. Prospective follow-up has shown progression of sub-threshold bipolarity to full-blown bipolar disorders. There has been great momentum in the clinical literature to study the various forms of the bipolar spectrum, which, in addition to the well-known types I and II in the DSM-IV and ICD-10 terminology, include depressions with shorter hypomanias, hypomanias elicited by antidepressant treatment, depressions arising from various bipolar temperaments such as the cyclothymic and the hyperthymic, as well as depressions with intra-episode hypomania (depressive mixed state). Despite criti-cism from some quarters, bipolar validation has been achieved for most of these forms in rigorously conducted studies coming from var-ious clinics in the world, particularly the United States, Italy, Ger-many, Switzerland and Hungary, as well as two national studies from Poland and France. Other proposed bipolar concepts refer to issues that have to do with “unipolar” depressions with high recurrence, atypical depression, seasonality, early age at onset, depressive and dysthymic states with bipolar family history, and affective states occurring in the setting of multiple anxiety disorders, as well as those in the post-partum period. In addition, controversial proposals have been made to hypothesize that borderline personality disorder, disso-ciate states, polysubstance abuse, particularly cocaine and stimulant abuse, might be related to the bipolar spectrum. Other “candidates” for the bipolar spectrum include affective comorbidity with migraine, eating disorders, gambling and a variety of impulse-control disorders. This is a large terrain and beyond the conventional literature, but of major significance for public health, clinical psychiatry, psychiatric theory and research methodology, including genetics. Thus, the field has progressed to the point of proposing some “soft” bipolar condi-tions as behavioral endophenotypes for bipolar disorder, for which genetic loci have been proposed in preliminary studies. While uncrit-ical acceptance of such a broad spectrum (or spectra) is not justified, criticisms of the bipolar spectrum without adequate familiarity of the entire literature are equally unwarranted. Much of what has driven treatment in practice has involved applying what works for the hard spectrum to the soft spectrum and beyond. Such therapeutic applica-tion, currently largely the domain of clinical judgment, should move to rigorous therapeutic trials in the service of public health, as it is happening in such fields as diabetes and hypertension. Primary and secondary prevention, including that of suicidal behavior, is an elo-quent driving force to address the spectrum of therapeutic challenges in psychiatry in this broad domain – challenges which are no less in magnitude than those in medicine at large.

TL4.

PHARMACOTHERAPY OF BINGE EATING

DISORDER

S.L. McElroy

Lindner Center of HOPE, Mason, OH; University of Cincinnati College of Medicine, Cincinnati, OH, USA

Binge eating disorder (BED) is the most common eating disorder. Patients with BED engage in frequent, recurrent episodes of binge eating without the compensatory weight-loss behaviors of bulimia nervosa or anorexia nervosa. Many of these patients suffer from mood symptoms or disorders and/or obesity. A growing number of

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pharma-cologic treatment options are now available to treat BED. These agents include selective serotonin reuptake inhibitors, the anti-obesi-ty agent sibutramine, and the anticonvulsant topiramate. This paper reviews the current clinical evidence for these and other medications in the treatment of BED.

TL5.

ENVIRONMENTAL CAUSES OF MENTAL DISORDER

M. Rutter

Institute of Psychiatry, London, UK

Half a century ago, there was a general acceptance of the view that environmental causes of mental disorder were strong and determina-tive. That view has been seriously challenged and it has become clear that the strong and deterministic notion of environmental causation was extremely misleading. Nevertheless, powerful research strategies have demonstrated the reality and importance of environmental cau-sation. This paper reviews the challenges and how they have been met; summarises the ways in which the early views have had to be modified; and indicates the current state of the art and the challenges that remain. Six issues constitute the main focus: a) the identification of key elements of risk, together with the appreciation that the casual effects may be prenatal as well as postnatal, and include both physi-cal and psychosocial hazards; b) the recognition that with multifacto-rial disorders there cannot be any single “basic” cause; rather the need is to identify key individual causal components and the direct and indirect pathways involved in the causal process; c) the reality of reverse causation, as exemplified by child effects on parenting; d) the need to consider possible genetic mediation of risks associated with specific environments; e) the role of “natural experiments” in testing causal inferences; f) the heterogeneity of response to environmental risk, the reality of resilience and the importance of the effects of envi-ronments on biology and the need to consider how “envienvi-ronments get under the skin”.

TL6.

THE CAUSES OF SCHIZOPHRENIA: THE STRIATUM

AND THE STREET

R.M. Murray

Institute of Psychiatry, London, UK

Much evidence suggests that the final common pathway to at least the positive symptoms of schizophrenia is dopamine dysregulation in the striatum. It is clear that an individual can develop this dysregulation consequent upon a number of different aetiological factors. Firstly, we have known for many years that inheritance contributes, and the evi-dence from the plethora of molecular studies over the last 6 years sug-gests that in most cases this operates through the interaction of a num-ber of genes of small effect. However, in a small proportion of cases, a copy number variation may play a major role possibly through impair-ing neurodevelopment. Certainly, some pre-schizophrenic children have cognitive and neuromotor impairments, and at first presentation, many individuals with schizophrenia have obvious brain structural and neuropsychological abnormalities. Furthermore, the risk-increas-ing effect of obstetric complications has been demonstrated for schiz-ophrenia, and these are known to be associated with both structural brain and cognitive abnormalities and with dopamine dysregulation. Thus, a second aetiological pathway implicates deviant neurodevel-opment. The excessive use of stimulant drugs and cannabis also increases risk of schizophrenia, and once again this appears to be via

their effect on striatal dopamine. Finally, there is increasing evidence implicating exposure to a number of social factors, including migra-tion, urbanisamigra-tion, and possibly childhood maltreatment. Of course, in many patients, more than one of these risk pathways is involved, and a combination of genetic, developmental and social factors proj-ect the individual over the threshold into illness.

TL7.

LONG-TERM MANAGEMENT OF DEPRESSION:

THE ROLE OF PHARMACOTHERAPY

AND PSYCHOTHERAPIES

M.E. Thase

University of Pennsylvania School of Medicine and Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA

This paper deals with the treatment of recurrent major depressive dis-order, focusing on strategies for prevention. There is broad consensus in practice guidelines that virtually all patients who respond to anti-depressant medications should receive a 6 to 9 month course of con-tinuation phase therapy to reduce the risk of relapse and that patients who have experienced three or more lifetime depressive episodes should receive a longer course of maintenance phase therapy to pre-vent recurrent illness. For those who do not obtain a full remission during acute phase therapy, there is increasing evidence that simply continuing the incompletely effective strategy is not sufficient to off-set the risk of relapse. With respect to maintenance phase therapy, there are surprisingly few studies of truly long-term courses of phar-macotherapy (i.e., across 2 or more years). It does appear that all medications with established short-term efficacy are also significantly more effective than placebo for prevention of relapse or recurrence. There is also evidence that various forms of cognitive behavior thera-py (CBT) have some degree of enduring prophylactic efficacy and may reduce the risk of recurrent illness following withdrawal of anti-depressant medications. Although studies of interpersonal psy-chotherapy (IPT) have yielded mixed results, the value for ongoing monthly sessions of IPT – in lieu of pharmacotherapy – has been shown in studies of adults under the age of 70, particularly when ther-apeutic focus is maintained on key areas of interpersonal vulnerabili-ty. Areas of controversy are also discussed, including questions per-taining to tachyphylaxis and whether or not the benefit-risk profile of longer-term antidepressant therapy has been exaggerated.

TL8.

WHAT IS A MOOD STABILIZER?

P.E. Keck, Jr.

Lindner Center of HOPE and University of Cincinnati College of Medicine, Cincinnati, OH, USA

The term “mood stabilizer” first entered the scientific lexicon in 1960, and did not refer to lithium, but rather to an obscure first generation antipsychotic agent then in development. This may have been pre-scient, however, as pharmacologic agents from different classes and different therapeutic designations have increasingly come to be described as mood stabilizers. Mood stabilizers have, in turn, been conceptualized as treatments for bipolar disorder, although the course of major depressive disorder for many patients suggests that this latter illness could benefit from mood stabilizing concepts as well. This paper considers the question of what a mood stabilizer is in the context of definitions formulated by investigators in the field of bipolar disorder, and in the light of evidence from randomized,

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con-trolled trials of treatments for the three acute mood episodes of bipo-lar disorder – mania, mixed states, and depression – and the preven-tion of symptomatic and syndromic relapses and recurrences of these mood states.

TL9.

MEDICAL BURDEN IN BIPOLAR DISORDER

D.J. Kupfer

Western Psychiatric Institute and Clinic, Pittsburgh, PA, USA

From a world public health perspective, bipolar disorder is one of the ten most disabling conditions. In the last decade, several impor-tant issues have emerged: a) The increasing awareness that bipolar disorder is associated with a medical burden from both concurrent medical disease and the adverse potential effect of the treatments used for bipolar disorder; routine medical screening needs to be implemented. b) The ongoing lack of complete recovery and full restorative and functioning is associated with increased medical and psychiatric comorbidity; the regular use of psychosocial approaches is needed. c) The presence of risk factors including obesity, nicotine, and drug use accelerate an overall increase in morbidity and mortal-ity. d) New comprehensive and integrated psychiatric/medical treat-ment approaches are needed. These recommendations are supported by data demonstrating that the increased medical comorbidity leads to slower treatment response of bipolar episode, especially depres-sion, as well as earlier recurrence. The presence of the metabolic syn-drome necessitates an integrated care model for bipolar disorder which seeks to positively influence modifiable medical risk factors, medical and psychiatric diseases, as well as to improve sleep/wake and social rhythms, and overall functioning. These customized treat-ment strategies include monitoring medical disease outcomes and medical risk factors. The following research and clinical questions emerge from current studies. How do we prevent acute illness from becoming chronic? Can early intervention prevent “comorbid accu-mulation”? And finally, how can we identify subgroups with circadi-an fragility or vulnerability as well as subgroups most “prone” to develop high metabolic risk profiles?

TL10.

GETTING THE EVIDENCE FOR EVIDENCE BASED

CARE OF DEPRESSION: HOW TO NARROW

THE KNOWLEDGE GAP

A.J. Rush

Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA

Clinicians and their depressed patients make treatment decisions everyday, which rest on the answers to critical clinical questions based more on “best guesses” than on empirical evidence in many instances. For example, how long should a patient be treated to determine that remission will not occur? Which clinical features, if any, recommend one treatment over another? Yet, answers to these critical questions profoundly affect both how treatment is delivered and its outcomes. This paper highlights and prioritizes these clinical questions and the available evidence to address them. The limitations both in what we know now and in how we gather evidence to answer better these questions in the future are discussed. Changes in how we report research results to better inform clinicians are also suggested. In addi-tion, suggestions to revise our current practice procedures in order to get more valid answers to these questions in more rapid and effective

ways are provided. The potential value of widely implementing meas-urement-based care, a uniform outcome recording system, and in establishing simple patient registries to address several of these issues is discussed. Finally, new clinically useful and “patient friendly” study designs illustrate potential ways to gather the evidence that we so des-perately need to put valid evidence into evidence-based care.

UPDATE LECTURES

UL1.

HOW DO WE CHOOSE MEDICATIONS

FOR PSYCHIATRIC PATIENTS?

R.J. Baldessarini

Harvard Medical School and McLean Hospital, Belmont, MA, USA

Most psychotropic drugs are palliative and not highly selective for particular disorders: “antipsychotics” are excellent antimanics, most “antidepressants” could as well been labeled “anxiolytics”, and drugs for epilepsy are used for mood disorders. Most are selected by a mix of addressing syndromes and symptoms. Research findings have a limited impact on practice. Current clinical research is highly indus-trial, oriented more toward licensing and marketing than questions of interest to clinicians and patients, and innovation plus marketing strongly influence drug choice. Clinical consideration of specific treatments typically focuses first on what is relatively simple to use and acceptable to patients: a need for regular medical monitoring or blood tests is a potent disincentive, given simpler or safer options. As examples, tricyclic antidepressants were displaced by the easier-to-use, but not more effective, selective serotonin reuptake inhibitors; lithium nearly disappeared in the US as seemingly simpler, safer anti-convulsants and antipsychotics became available, and easily-used valproate displaced lithium even without long-term research support or regulatory approval for prophylaxis. Regional and national differ-ences in drug choices suggest effects of culture or training, including marketing influences of “thought leadership”, and even fads. Confu-sion also is generated by plastic, market-oriented terms such as “major depression”, “antidepressant”, and mood stabilizer. Notably, depressive features of bipolar disorder are commonly conflated with unipolar major depressive disorder, even though the syndromes are very different and require dissimilar treatments, although they are very commonly treated with “antidepressants”.

UL2.

PSYCHOTHERAPIES: WHAT WORKS FOR WHOM?

P. Fonagy

University College London, London, UK

Sixty years of research have established psychological therapies as an effective part of our therapeutic armamentarium of psychiatry in work with most mental disorders. This paper reviews the indications for specific types of psychological therapy for all common mental dis-orders including the psychoses, non-psychotic disdis-orders and Axis II disorders. There is also an accumulating body of evidence that sug-gests psychological interventions in the context of prevention of men-tal disorder. However, while there appears to be no shortage of poten-tially effective interventions, we are not much closer to being able to answer the question: “What is most likely to work for whom?” in

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relation to particular treatments and models of disorder. The question of the effectiveness of psychotherapy has shifted from the issue of out-come to the issue of mechanism. A range of treatments work, but do they work as well as they could? This question cannot be answered unless we understand more about the process of psychological disor-der and the way “disease process” interfaces with therapeutic mecha-nism. This paper identifies some examples where this reframing of the outcomes question has been helpful in improving the efficacy and generalisability of psychological treatment.

UL3.

VALUES-BASED PRACTICE AND PSYCHIATRIC

DIAGNOSIS: BRINGING VALUES AND EVIDENCE

TOGETHER IN POLICY, TRAINING AND RESEARCH

K.W.M. Fulford

Universities of Oxford and Warwick, Department of Health, UK

In the current climate of dramatic advances in the neurosciences, it has been widely assumed that the diagnosis of mental disorder is a matter exclusively for value-free science. Using a case history, this paper shows how, to the contrary, values come into the diagnosis of mental disorders directly through the criteria at the heart of psychia-try’s most scientifically-grounded classification, the American Psychi-atric Association’s DSM. Various possible interpretations of the importance of values in psychiatric diagnosis are outlined. Drawing on work in the Oxford analytic tradition of philosophy, it is shown that, properly understood, diagnostic values in psychiatry are com-plementary to evidence-based science. This interpretation opens up psychiatric diagnostic assessment to the resources of a new skills-based approach to working with complex and conflicting values called “values-based practice”. The principles of values-based prac-tice are briefly introduced and then illustrated with a number of recent developments in policy and service development in the UK’s Department of Health and internationally. In particular, a current Department of Health programme on best practice in diagnostic assessment is outlined. This programme illustrates how person-cen-tred diagnostic assessment depends crucially on combining evidence-based with values-evidence-based approaches.

UL4.

RECOVERY AND POSITIVE PSYCHOLOGY:

EMPIRICISM OR ATTITUDE?

S.G. Resnick

VA Connecticut Healthcare System, West Haven, CT, USA

Recovery is a grass-roots movement derived from the personal narra-tives of those living with a mental illness. Despite the increasing pres-sure to provide “recovery-oriented” services and “recovery-informed” research, the meaning of the word recovery is still unclear. We do not have consensus on the definition of recovery, we have yet to identify factors that promote it, and we lack well-validated measurement tools that help us know when we have achieved it. Fortunately, the positive psychology movement may provide us with some guidance in addressing these unknowns. Positive psychology seeks to answer the same basic question as the recovery movement, namely, how can we learn to live happy, gratifying, and meaningful lives? But, unlike the recovery movement, positive psychology was founded by academics, its concepts are derived through quantitative research, and the move-ment keeps empiricism at its core. Thus, the positive psychology movement is poised to offer a complementary view to the grass-roots

perspective of the recovery movement. Yet, despite their increasing popularity and prominence, these two complementary movements continue to develop independently of one another, with minimal awareness of the other’s existence. This paper briefly reviews the state of the research in the recovery movement, followed by a focus on potential areas of synergy between the two movements for research and practice.

UL5.

STEPS, CHALLENGES AND MISTAKES TO AVOID

IN THE DEVELOPMENT OF COMMUNITY MENTAL

HEALTH CARE: A FRAMEWORK FROM

EXPERIENCE

G. Thornicroft, M. Tansella

Health Service and Population Research Department, Institute of Psychiatry, King’s College London, UK; Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Italy

This paper summarises our own accumulated experience from devel-oping community-orientated mental health services in England and Italy over the last 20-30 years. From this we have provisionally con-cluded that the following issues are central to the development of bal-anced mental health services: a) services need to reflect the priorities of service users and carers; b) evidence supports the need for both hospital and community services; c) services need to be provided close to home; d) some services need to be mobile rather than static; e) interventions need to address both symptoms and disabilities; and f) treatment has to be specific to individual needs. In this paper we consider ten key challenges that often face those trying to develop community-based mental health services: a) dealing with anxiety and uncertainty; b) compensating for a possible lack of structure in com-munity services; c) learning how to initiate new developments; d) managing opposition to change within the mental health system; e) responding to opposition from neighbours; f) negotiating financial obstacles; g) avoiding system rigidities; h) bridging boundaries and barriers; i) maintaining staff morale; and j) creating locally relevant services rather than seeking “the right answer” from elsewhere.

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EARLY INTERVENTION IN PSYCHIATRY

P.D. McGorry

ORYGEN Youth Health Research Centre, University of Melbourne, Australia

Mental and substance use disorders are among the most important health issues facing society. They are by far the key health issue for young people in the teenage years and early twenties and, if they per-sist, they constrain, distress and disable for decades. Epidemiological data indicate that 75% of people suffering from an adult-type psychi-atric disorder have an age of onset by 24 years of age, with the onset for most of these disorders – notably psychotic, mood, personality, eating and substance use disorders – mainly falling into a relatively discrete time band from the early teens up until the mid 20s, reaching a peak in the early twenties. In recent years, a worldwide focus on the early stages of psychotic disorders has improved the prospects for understanding these complex disorders and improving their short-and longer-term outcomes. This reform paradigm has also illustrated how a staging model may assist in interpreting and utilising biological data and refining diagnosis and treatment selection. There may be

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broader lessons for psychiatric research and treatment, particularly in the field of mood and substance use disorders. Furthermore, the cru-cial developmental needs of this age group are poorly met by existing service models and approaches. Young people need a different style and range of service provision in order to engage with and benefit from interventions. The need for structural reform and a long term research agenda is clear.

UL7.

IMPROVING COGNITIVE PERFORMANCE

AND REAL-WORLD FUNCTIONING IN PEOPLE

WITH SCHIZOPHRENIA

M.F. Green

Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, USA

Considerable efforts are underway to find new treatments for cognitive impairment in schizophrenia. These efforts have been stimulated by activities from the US National Institute of Mental Health (e.g., MATRICS and TURNS Initiatives) that have provided a pathway for approval of cognition-enhancing drugs. We present data on new phar-macological and behavioral interventions that are designed to enhance cognition and improve daily functioning. For pharmacological inter-ventions, the cognitive effects of second-generation antipsychotic medications and anti-dementia drugs in schizophrenia have been inconsistent and relatively disappointing. This situation has led to careful consideration of newer types of drugs. Proof of concept trials of drugs that act on novel mechanisms (e.g., alpha 7 nicotinic receptor, AMPA receptor, neural protective agents, glycinergic agents) are start-ing to emerge and are showstart-ing mixed results as cognitive enhancers. Several behavioral training interventions have been implemented, including cognitive remediation and errorless learning. These are showing success in improving outcomes when combined with voca-tional rehabilitation. Social cognitive deficits in schizophrenia have become a relatively new target for intervention. Recently developed training programs for social cognition are showing promise. Overall, this is a time of considerable innovation in both the pharmacological and behavioral treatments for schizophrenia.

UL8.

EVIDENCE-BASED COMPREHENSIVE

MANAGEMENT OF BIPOLAR DISORDER

E. Vieta

Bipolar Disorder Program, University of Barcelona, Spain

The successful treatment of bipolar disorder heavily depends on hav-ing a medical model of the disease in mind. The cornerstones of such treatment are evidence-based psychopharmacology and psychoedu-cation. The treatment of mania can be addressed with antipsychotics, as all of them have antimanic properties and may have a faster onset of action than lithium or anticonvulsants such as valproate or carba-mazepine. The choice of the antipsychotic should rather rely on the safety/tolerability profile and on the availability of long-term data for that specific compound. As far as possible, compounds with low extrapyramidal and metabolic side effects liability should be pre-ferred. The treatment of bipolar depression may be addressed with a more heterogeneous range of medications, including quetiapine, lam-otrigine, the combination of olanzapine and fluoxetine, and other combinations of drugs. The long-term treatment of bipolar disorder is crucial for a good clinical outcome and to prevent cognitive and

func-tional impairment, and may involve lithium, lamotrigine, valproate, carbamazepine, quetiapine, aripiprazole, olanzapine, and combina-tions of these and other agents. Long-acting risperidone may be used in highly relapsing patients, and electroconvulsive therapy or clozap-ine may be a good choice in treatment-resistant cases. Education on the disease aimed at the patient and also at the family, caregivers, and significant others is also essential for a good outcome. Enhancing ill-ness awareill-ness improves treatment adherence and helps to cope with stigma; teaching patients on the recognition of early warning signs of relapse and on effective seek for help may be particularly effective to prevent relapse into mania; helping patients to understand the poten-tial impact of legal and illegal drugs on the course of their condition, promoting healthy sleep and eating habits, and reinforcing resilience may be very useful to decrease their vulnerability to stressors and to keep them well.

UL9.

MANAGEMENT OF PATIENTS

WITH CO-OCCURRING SUBSTANCE ABUSE

AND SEVERE MENTAL DISORDER

R.E. Drake

Dartmouth Psychiatric Research Center, Dartmouth Medical School, Lebanon, NH, USA

This paper discusses the clinical implications of past and current research on co-occurring substance abuse and severe mental disorder. Past research findings include: a) co-occurring disorders are modal; b) co-occurring disorders are costly; c) parallel treatments are ineffec-tive; d) integrated treatment are more effecineffec-tive; e) integrated dual diagnosis treatment fidelity is important. These findings suggest that all mental health clinicians need to be skilled in assessing and treat-ing co-occurrtreat-ing disorders and that all mental health programs need to be co-occurring disorders programs. Recent research points to sev-eral new findings: a) recovery is multi-dimensional; b) types of inter-ventions have specific effects; c) group interinter-ventions and residential programs are the most effective modalities for addressing co-occur-ring substance abuse; d) relapse prevention is correlated with safe housing, employment, relationships, and maintenance treatment; e) supported employment effectively provides a critical recovery compo-nent: structured and meaningful activity; f) subtypes of co-occurring disorders patients have different treatment needs and different trajec-tories of recovery. These findings support using client preferences for a variety of interventions; long-term programs; emphasizing groups, residential services, and supported employment; and developing per-son-centered algorithms for interventions. Several other research findings, related to families, trauma treatments, and other aspects of co-occurring disorders, are less clear.

UL10.

COMPREHENSIVE MANAGEMENT OF BORDERLINE

PERSONALITY DISORDER IN ORDINARY CLINICAL

PRACTICE

M.H. Stone

Department of Clinical Psychiatry, Columbia College of Physicians and Surgeons, New York, NY, USA

Within the past decade, manuals containing treatment guidelines have been developed for a number of the different, and currently pop-ular, approaches to the therapy of borderline personality disorder (BPD). Among these are manuals of transference-focused

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psy-chotherapy (TFP), an outgrowth of past works on psychoanalytically-oriented forms of therapy for this patient group; the closely related mentalization-based therapy (MBT) promulgated by Fonagy and his colleagues; dialectic behavior therapy (DBT), cognitive-behavior therapy (CBT), schema-based therapy (SBT), and supportive therapy. These different approaches have proven about equally effective in reducing the tendency to self-destructive behaviors (including suicide gestures) within about 8 to 12 months, in those BPD patients who manifest such behaviors. Long-term outcomes (5 or 10 years or more) have not been assessed for the various approaches, so we cannot claim that one method is superior across the board, with respect to the more important parameters of love, friendship, work, and hob-bies. Furthermore, the symptom improvement (fewer self-destructive acts, less depression, etc.) cannot be ascribed solely to the verbal psy-chotherapy approach, since antidepressant, mood-stabilizing, and other medications often play a decisive role, especially in the early phases of treatment, in reducing the “Axis-I” symptoms that invari-ably accompany cases of BPD. The typical BPD patient has problems in many spheres, and needs help in skill-building (DBT), in modifying unrealistic core-beliefs (SBT), in developing more adaptive relation-ships with others (TFP), in improving the capacity for self-relection (TFP and MBT), and in changing behavior along more adaptive and realistic lines (CBT). Limit-setting and crisis-intervention will be important modalities, especially at the outset (supportive therapy). What is called for is, ideally, an integrated form of therapy, along the lines advocated by Livesley, where one is trained in a particular ther-apeutic approach, but remains open to the advantages offered by the others, depending on the moment-to-moment needs of each BPD patient. Judicious shifting from one modality to another, as the occa-sion demands, while remaining firmly anchored in one’s original training and specialty, is the ideal strategy. This involves flexibility and respect for the other main approaches, besides the one in which therapists had their main training and early experience. Knowledge of, and respect for, the different psychopharmacological agents that may be effective in working with BPD patients are also crucial to the full and complete treatment of patients with this disorder.

UL11.

COMPARATIVE EFFICACY, EFFECTIVENESS

AND COST-EFFECTIVENESS OF ANTIPSYCHOTICS

IN THE TREATMENT OF SCHIZOPHRENIA

W.W. Fleischhacker

Department of Biological Psychiatry, Medical University of Innsbruck, Austria

The tremendous success of clozapine in the treatment of schizophre-nia has fostered the development of a number of second generation antipsychotics. These include amisulpride, aripiprazole, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone and zotepine. The advent of these drugs has refueled the interest in the pharmacological treatment of schizophrenia, where little progress had been made since the early 1970s. Next to control of positive symptoms comparable to the classical neuroleptic haloperidol, these new antipsychotics have opened new vistas into treatment areas that had been basically unresponsive to traditional neuroleptics, such as negative and depressive symptoms as well as cognitive dysfunctions. Safety concerns, traditionally focused on extrapyramidal motor symptoms, have shifted to other previously neglected areas, such as endocrine and sexual dysfunctions as well as disturbances in glucose and lipid metabolism. As these new medications are available at a considerably higher cost than their classical counterparts, a

discus-sion about cost-effectiveness arose. Health care providers, supported by critical scientists, who claim that the advantages of the new drugs over the older ones are too small to recommend them as first line treatments, are still restricting reimbursement of second generation antipsychotics in some countries. Taken all evidence together, it appears fair to say that the new medications have a considerable advantage over traditional antipsychotics with respect to the risk for both acute and chronic extrapyramidal motor side effects. This has been substantiated by almost every clinical trial available. On the other hand, one needs to consider the fact that some of the newer drugs have a significant risk to induce weight gain as well as distur-bances of glucose and lipid metabolism, although there is recent evi-dence that this may also hold true for some of the older antipsy-chotics, especially in younger patients. With respect to efficacy, the most up-to-date meta-analysis suggests a slight advantage of some of the newer generation antipsychotics over older drugs, with respect to both positive and negative symptoms, although some large scale prag-matic studies do not support this. This advantage seems to be partic-ularly relevant in first episode schizophrenia patients. As most of the cost-effectiveness studies have focused on direct treatment costs, we still await pharmacoeconomic comparisons between older and newer antipsychotics that include indirect costs, which largely drive the overall economic impact of schizophrenia. Lastly, subjective reports of patients’ well being and acceptance of medication also appear to favor the newer drugs. This should also be an important constituent of choice of treatment.

UL12.

THE ART AND SCIENCE OF SWITCHING

ANTIPSYCHOTIC MEDICATIONS

P.J. Weiden

Center for Cognitive Medicine, University of Illinois Medical Center, Chicago, IL, USA

The introduction of the newer atypical antipsychotic medications in the 1990s was the first major change in the psychopharmacologic treatment of schizophrenia in many years. Many patients previously treated with conventional antipsychotics showed marked improve-ment when switched to a new antipsychotic. It soon became apparent that there were certain barriers to making a successful switch between antipsychotics, with many patients becoming unstable and relapsing during switches. Now, over a decade has passed since the newer med-ications have become available, and basic switching techniques are better understood. However, new challenges have emerged as more antipsychotics become available, and the range of pharmacologic treatment options continues to expand. Rates of switching antipsy-chotics in United States outpatient practice settings have jumped from about 10% a year to over 30% a year. This paper focuses on recent developments in switching between the newer antipsychotics, in the light of new understanding from effectiveness trials such as the CATIE, and the potential exacerbation of medical risk factors associ-ated with some, but not all, of the newer medications. To address the problem of high rates of “failed” switches, this paper also reviews how differences in the pharmacologic and clinical profiles of newer antipsychotics influence switch strategy techniques.

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UL13.

COMBINED AND SEQUENTIAL TREATMENT

STRATEGIES IN DEPRESSION

AND ANXIETY DISORDERS

G.A. Fava

Affective Disorders Program, Department of Psychology, University of Bologna, Italy

There is increasing awareness that monotherapy (whether pharma-cotherapy or psychotherapy) is unlikely to yield full remission in mood and anxiety disorders. The joint use of psychotherapeutic and pharmacological strategies has produced limited benefits when the two treatments have been administered simultaneously. More promis-ing results have been obtained with their sequential combination, particularly when psychotherapeutic approaches have followed the administration of pharmacotherapy. In unipolar depression, there is substantial evidence that decreasing residual symptoms and/or increasing psychological well-being and coping skills in remitted patients may decrease relapse rate during follow-up up to 6 years. The sequential strategy does not fall within the realm of maintenance treatments. It is an intensive, 2-stage approach, which is based on the fact that addressing one dimension of illness after an earlier feature has improved can increase the likelihood of more complete and last-ing remission. The plannlast-ing of treatment in mood and anxiety disor-ders requires determination of the first line approach (e.g., pharma-cotherapy) and tentative identification of other areas of concern to be addressed by concomitant or subsequent treatment.

UL14.

MULTIMODAL MANAGEMENT OF ANOREXIA

AND BULIMIA NERVOSA

K.A. Halmi

Weill Medical College, Cornell University, New York, NY, USA

The allostatic model is useful to conceptualize the development of the multimodal management of anorexia and bulimia nervosa. Allostasis is a dysregulation of brain reward circuits in response to the failure of homeostasis, a self-regulating process for multi system coordination of an organism’s response to an acute challenge, starvation in anorex-ia nervosa (AN) and binge/purge behavior in bulimanorex-ia nervosa (BN). The state of allostasis reflects both genetic and environmental factors and the allostatic load represents the presence of excessive demand on regulatory systems. Multiple brain mechanisms could contribute to produce the allostatic state that underlies the severe psychopathol-ogy in anorexia and bulimia nervosa. Evidence exists for biological vulnerabilities and genetic factors leading to an allostatic state in these disorders. Dysfunction of neurotransmitters (serotonin, dopamine and norepinephrine) regulating eating behavior are pres-ent, as well as aberrations of neuropeptides (NYP, opioids, leptin, CCK, ghreline, melanocortins, adiponectin, agouti-related protein and BDNF) which affect eating. Genetic studies show significant linkage on chromosome 1 for restricting AN and on chromosome 10 for BN. The key multimodal elements in the treatment of AN and BN are commensurate with the allostatic model. Medical management requires weight restoration with nutritional rehabilitation, rehydra-tion and correcrehydra-tion of serum electrolytes. The core eating disorder psychopathology requires specific cognitive-behavioral therapy. Ado-lescents with eating disorders require family therapy. Comorbidities and severe impairment of function require pharmacotherapy. Few randomized controlled treatment trials exist to provide guidelines for treatment of AN. In the past 5 years, additional family therapy studies

and an olanzapine-placebo controlled trial have provided evidence for treatment of AN. In a recent trial, adolescents with BN were effec-tively treated with family therapy. Innovative treatments are especial-ly needed for adults with chronic AN. Attention must be focused on resistance to treatment and extremely high dropout rates.

UPDATE SYMPOSIA

US1.

THE EVOLVING SCIENCE AND PRACTICE

OF PSYCHOSOCIAL REHABILITATION

US1.1.

DEVELOPMENTS IN PSYCHOSOCIAL

REHABILITATION: INNOVATION OR RE-INVENTION?

R. Warner

Department of Psychiatry, University of Colorado Health Sciences Center, Denver, CO, USA

Since the Second World War, we have seen tremendous changes in psychosocial rehabilitation methods. The development of the thera-peutic community, dramatic reforms in hospital care and early dis-charge to the community have led to the dissolution of large psychi-atric institutions across the developed world. The psychosocial club-house has proven useful in tackling the powerlessness, boredom and social exclusion that many people with mental illness experience when they achieve a stable existence in the community. Supported employ-ment and social firms have helped address the problem of unemploy-ment. Cognitive behavioral therapy seeks to decrease the discomfort created by persistent psychotic symptoms, and cognitive remediation aims to reduce the handicap caused by the cognitive symptoms of psy-chosis. Which of these developments are truly an innovation and which are a reformulation of an earlier approach? What social, politi-cal and economic factors drive the emergence of new rehabilitation methods? What are the next barriers we must confront?

US1.2.

VOCATIONAL REHABILITATION IN EUROPE:

LESSONS FROM THE EQOLISE TRIAL

T. Burns

University of Oxford, UK

The severely mentally ill invariably have low rates of employment despite extensive rehabilitation efforts. Recently there has been a shift in vocational rehabilitation in mental health, away from the more tra-ditional structured rehabilitation programmes (often referred to as “train-and-place”) to more direct “place and train” approaches. The most widely researched of these approaches is independent place-ment and support (IPS) and several US randomized controlled trials have demonstrated very significant advantages over high-quality tra-ditional rehabilitation measured as obtaining open employment. However, we have learnt from bitter experience that complex com-munity interventions do not always work as well when translated to different social contexts, and the European employment situation is very different to that in the US. We conducted a multisite trial of IPS in Europe. The trial involved a random allocation of 302 psychotic subjects, 50 from within each of six European countries, to either IPS or local standard vocational rehabilitation. Subjects were followed up for 18 months by independent researchers. Primary outcome was

Zonisamide augmentation in poor- or non-responder patients treated with duloxetine for a major depressive episode

WP

W

orld

P

sychiatry

OFFICIAL JOURNAL OF THE WORLD PSYCHIATRIC ASSOCIATION (WPA)

Volume 8, Supplement 1

February 2009

WORLD PSYCHIATRIC ASSOCIATION

INTERNATIONAL CONGRESS

“TREATMENTS IN PSYCHIATRY: A NEW UPDATE”

April 1-4, 2009

Florence, Italy

ABSTRACTS

The World Psychiatric Association (WPA)

World Psychiatry

World Psychiatry is indexed in PubMed, Current Contents/Clinical Medicine, Current Contents/Social

and Behavioral Sciences, Science Citation Index, and EMBASE.

WORLD PSYCHIATRIC ASSOCIATION

INTERNATIONAL CONGRESS

"TREATMENTS IN PSYCHIATRY:

A NEW UPDATE"

April 1-4, 2009

Florence, Italy

PRESIDENT OF THE CONGRESS

CONTENTS

ESI

TOP-CITED SCIENTIST LECTURES

TL1.

THE TREATMENT GAP IN PSYCHIATRY

TL2.

PSYCHIATRIC GENETICS: A CURRENT

PERSPECTIVE

TL3.

BIPOLARITY: A BROAD SPECTRUM (SPECTRA)

IN SEARCH OF TREATMENT

TL4.

PHARMACOTHERAPY OF BINGE EATING

DISORDER

TL5.

ENVIRONMENTAL CAUSES OF MENTAL DISORDER

TL6.

THE CAUSES OF SCHIZOPHRENIA: THE STRIATUM

AND THE STREET

TL7.

LONG-TERM MANAGEMENT OF DEPRESSION:

THE ROLE OF PHARMACOTHERAPY

AND PSYCHOTHERAPIES

TL8.

WHAT IS A MOOD STABILIZER?

TL9.

MEDICAL BURDEN IN BIPOLAR DISORDER

TL10.

GETTING THE EVIDENCE FOR EVIDENCE BASED

CARE OF DEPRESSION: HOW TO NARROW

THE KNOWLEDGE GAP

UPDATE LECTURES

UL1.

HOW DO WE CHOOSE MEDICATIONS

FOR PSYCHIATRIC PATIENTS?

UL2.

PSYCHOTHERAPIES: WHAT WORKS FOR WHOM?

UL3.

VALUES-BASED PRACTICE AND PSYCHIATRIC

DIAGNOSIS: BRINGING VALUES AND EVIDENCE

TOGETHER IN POLICY, TRAINING AND RESEARCH

UL4.

RECOVERY AND POSITIVE PSYCHOLOGY:

EMPIRICISM OR ATTITUDE?

UL5.

STEPS, CHALLENGES AND MISTAKES TO AVOID

IN THE DEVELOPMENT OF COMMUNITY MENTAL

HEALTH CARE: A FRAMEWORK FROM

EXPERIENCE

UL6

EARLY INTERVENTION IN PSYCHIATRY

UL7.

IMPROVING COGNITIVE PERFORMANCE

AND REAL-WORLD FUNCTIONING IN PEOPLE

_{TOP-CITED SCIENTIST LECTURES}