Major depressive disorder is frequently diagnosed based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), which emphasises depressed mood and anhedonia as key symptoms. While the increased negative affect is well represented in the standard questionnaires, the presence of positive affect is usually not assessed. Furthermore, the reliability of the DSM-5 as a diagnostic instrument has been challenged. Recent field trials have indicated that the

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... t reliability of the DSM-5 for major depressive disorder is 'questionable',1 ie the degree to which two clinicians could independently agree on the presence or absence of selected DSM-5 diagnoses in the same patient. Furthermore, patients and clinicians regard different symptoms as a priority when considering cure.2 While patients consider items like 'meaningful life', positive affect and 'concentration' as most important, clinicians generally perceive depressive symptoms and impaired functioning as the most important. This is of relevance because poor physician-patient agreement regarding the relative importance of these symptoms is associated with a worse clinical outcome for three variables: anxiety, positive affect and social relationships. 3 Clinical experience and the history of psychopharmacology (including 30 years of marketing of antidepressants) illustrate that depression is more than just low mood. In addition to drugs that broadly affect depressive symptoms, a range of antidepressants are now available with different pharmacological actions, developed to target specific symptoms in depression beyond low mood. These symptoms include anxiety symptoms (eg selective serotonin reuptake inhibitors), physical symptoms (eg duloxetine), positive affect (eg agomelatine) and cognitive symptoms (eg vortioxetine).4 Exploring the historical use of antidepressants highlights how depression is a disease with multiple dimensions and may help further our understanding of this complex disorder, and of the specific profiles of different antidepressants. Abstract Cognitive dysfunction in depression can include biases towards negative emotional information and deficits in memory, attention and executive function. In depression, experimental models have revealed early effects of antidepressants on emotional biases.1 One week of selective serotonin reuptake inhibitor (SSRI) treatment reduced the recognition of negative versus positive affective facial expressions, accompanied by reduced amygdala response to fearful faces. These early changes in emotional processing predict a reduction in symptoms after 6-8 weeks of treatment and have led to the hypothesis that early reduction in affective bias is a key mechanism of antidepressant drug effects.1 The effects of SSRIs on other cognitive deficits in depression are less consistent; improvements can often be accounted for by mood effects. The multimodal antidepressant vortioxetine improved executive function in depressed patients and these effects may be direct rather than via symptom improvement.2,3 In support of these clinical observations, we found an early effect of vortioxetine in individuals remitted from depression and healthy volunteers. Compared to placebo, vortioxetine facilitated subjective and objective measures of cognitive function while reducing activation in the dorsolateral prefrontal cortex and hippocampus during the n-back working memory task. This suggests that vortioxetine modulates neural responses across a circuit subserving working memory conversely to the changes described in depression. Abstract | 3 Compared to clinical rating scores, objective measurement of cognitive function with behavioural assessment and neuroimaging may provide more information about the early effects of antidepressants. These early effects may be fundamental to later effects on patient functioning in depression. Abstract Cognitive dysfunction has been recognised as an important feature of major depression since its earliest historical descriptions. The prominence of mood symptoms during the acute state led to the assumption that cognitive dysfunction is an epiphenomenon of depression. However, there are inconsistencies with this viewpoint. Cognitive dysfunction remains present during remission of depressive symptoms and the magnitude of cognitive dysfunction explains much of the residual functional disability seen in depression.1 Antidepressant therapies offer only limited benefit in cognitive function for the most part,2 where such effects have been shown, and some of these cognitive effects appear to be partially independent of mood effects.3,4 When evaluating cognition in depression, it is important to appreciate that the illness may be responsible for a change from a previously higher level of cognitive functioning, and it is this change, rather than performance relative to published norms, that is most clinically meaningful. For example, a patient whose performance may have been above the mean who is now performing at the mean should be regarded as suffering from cognitive dysfunction, even though test performance falls within the normal range. This situation represents a challenge in the clinic that may be best overcome by careful interview of the patient about performance-capacity changes associated with the onset of depression that may arise from emergent cognitive dysfunction. Similar interviewing, or alternatively cognitive testing, can then be used to track change in the presence of treatments. In this presentation, both 'direct' and 'indirect' treatment effects on cognitive dysfunction in depression will be described, and evidence presented. By way of context, a general description of cognitive dysfunction will be offered, including a discussion of cognitive dysfunction in other psychiatric diseases (in particular, schizophrenia and attention-deficit hyperactivity disorder). In addition, the psychometric requirements for reliable measurement of cognitive change will be presented, including specific tools, and their potential for clinical application in depression. Abstract Virtually all patients with schizophrenia will relapse if antipsychotic treatment is stopped following a psychotic episode, and in the long term many patients will experience multiple relapses. 1,2 Relapse may occur suddenly, within weeks of antipsychotic discontinuation, and with limited early warning signs. 3 Relapse is harmful to the patient and results in treatment resistance, such that higher doses of antipsychotic, and a longer treatment period, are required to regain symptomatic control. 2 Furthermore, relapse has serious psychosocial consequences, including distress to patients and carers, disruption of relationships, education, and employment, suicidal and homicidal behaviour, increased stigma, and increased economic burden. 4 Thus, patient health-related quality of life (HRQoL) is adversely affected, and the longer the length of the illness, the worse the HRQoL. 5 Antipsychotic medication is efficacious for preventing relapse when taken correctly, but partial or non-adherence to oral antipsychotics is common. 6 Non-adherence to medication results in poor health outcomes, and increased healthcare costs. 7 Treatment adherence also correlates with HRQoL in patients with schizophrenia, and therefore improving adherence to medication is a key approach to improving HRQoL. 8 Thus, the development of antipsychotic treatments that can minimise non-adherence provides a valuable contribution to reducing the incidence of relapse and improving long-term HRQoL and functioning, in patients with schizophrenia. References 1. Emsley R, Oosthuizen P, Koen L, Niehaus D, Martinez L. Comparison of treatment response in second-episode versus first-episode schizophrenia. J Clin Psychopharmacol 2013; 33 (1): 80-83. 2. Lieberman JA, Alvir JM, Koreen A, Geisler S, Chakos M, Sheitman B, Woerner M. Psychobiologic correlates of treatment response in schizophrenia. Neuropsychopharmacology 1996; 14: 13S-21S. 3. Emsley R, Oosthuizen PP, Koen L, Niehaus DJ, Martinez G. Symptom recurrence following intermittent treatment in first-episode schizophrenia successfully treated for 2 years: a 3-year open-label clinical study. J Clin Psychiatry 2012; 73 (4): e541-e547. 4. Emsley R, Fleischhacker WW. Is the ongoing use of placebo in relapse-prevention clinical trials in schizophrenia justified? Schizophr Res 2013; 150 (2-3): 427-433. 5. Bobes J, Garcia-Portilla MP, Bascaran MT, Saiz PA, Bousoño M. Quality of life in schizophrenic patients. Dialogues Clin Neurosci 2007; 9 (2): 215-226. 6. Citrome L. New second-generation long-acting injectable antipsychotics for the treatment of schizophrenia. Expert Rev Neurother 2013; 13 (7): 767-783. 7. World Health Organization (WHO). Adherence to long-term therapies: evidence for action. © World Health Organization 2003. 8. Hayhurst KP, Drake RJ, Massie JA, Dunn G, Barnes TR, Jones PB, Lewis SW. Improved quality of life over one year is associated with improved adherence in patients with schizophrenia. Eur Psychiatry 2014; 29 (3): 191-196. Abstract Evidence is emerging that relapse prevention after the initial onset of psychosis may confer significant clinical and functional benefits. Furthermore, a longer duration of untreated psychosis is associated with worse long-term outcome. Thus, prompt initiation of treatment is a vital component of optimal care early in the course of psychosis. Of particular importance is medication adherence, as non-adherence to antipsychotic medication has a significant negative impact on treatment response, is a significant predictor of poorer outcomes and is the biggest predictive factor of relapse after a first episode of psychosis. Continuous integrated care for people with schizophrenia is the 'gold standard' that many national and international guidelines recommend. But the question remains, how can this be achieved in everyday practice? Dr Maju Mathews (Janssen) will discuss the latest developments in both psychosocial and pharmacological treatments and will highlight the importance of continuous monitored integrated care. Abstract This session will take the innovative format of an interactive case study, of which audience members can directly influence the outcome. A short case study will be presented: a patient who has experienced several relapses. The audience members can then vote on how they would proceed at several key decision points. At each of these points, the audience's response will determine the next aspect of the case to be presented. The session will present scenarios such as non-adherence to treatment, and the challenges involved when a patient refuses to accept their diagnosis. How the audience decides to deal with these scenarios is up to them! Dr David Castle (Australia) will be on hand to guide the audience and will provide best-practice examples from real clinical practice showing how to deal with these scenarios -after the audience has made their choice, of course! Abstract Depression and anxiety frequently occur together in clinical practice, and this presentation will discuss the nature of interaction of these conditions. Within major depressive disorder (MDD), the DSM-5 includes a 'with anxious distress' specifier for patients experiencing at least two anxiety symptoms during the majority of days of a major depressive episode. Anxious distress is a prominent feature of MDD, in primary care and speciality mental health settings. In total, the DSM-5 outlines 12 types of anxiety disorder and eight types of depressive disorder; however, there is considerable overlap between these conditions. Some symptoms occur in both anxiety and depression, for example, fatigue, dysphoria, irritability, sleep disturbance, appetite disturbance, and sensitivity to criticism. Indeed, there is debate as to whether depression and anxiety are distinct disorders, or whether they are overlapping syndromes, which share a common neurobiology. Patients with depression and comorbid anxiety disorder, compared with depression without anxiety, have a less favourable prognosis. This is due to multiple factors, including more severe depressive symptoms, poorer response to medication, longer time to response and remission, functional impairment, and increased suicidality. When anxiety Abstract | 7 and depression are present together, a greater impairment in mental health and functioning is observed than for either condition by itself. Thus, not only are symptoms of depression and anxiety highly overlapping and difficult to dissect, they are characteristic of a more severe, harder-to-treat illness. Abstract In MDD, high levels of anxiety are associated with increased suicide risk, longer duration of illness, and a greater likelihood of non-response to treatment. Unlike pure depressive episodes, which are generally recognised in primary care, depression with anxiety symptoms or comorbid anxiety is under-diagnosed. Considering that patients with MDD are highly likely to suffer from anxiety symptoms or a comorbid anxiety disorder, screening for anxiety in patients with MDD, and vice versa, should become routine in clinical practice. This presentation will discuss the challenges associated with diagnosing and treating depression with anxiety. There is currently a need for treatments with proven efficacy in treating depression with anxiety. Anxious depression is associated with a lower likelihood of remission following cognitive therapy. In the STAR*D study, remission with citalopram treatment was significantly less likely, and took longer to occur, in patients with anxious depression compared with non-anxious depression. Furthermore, pooled data from five clinical trials have shown that patients with severe non-anxious depression are more responsive to SSRI treatment, compared with patients with severe anxious depression. Published data on the efficacy of pharmacological treatment of depression with anxiety will be reviewed. In conclusion, anxiety in MDD is under-diagnosed, and MDD with anxiety is more difficult to treat. However, treatment can be successful with the appropriate strategy, including choice of pharmacological treatment. Abstract Social anxiety disorder (SAD) is a highly prevalent disorder, which is associated with a considerable functional burden. However, low rates of presentation, recognition and diagnosis mean that a large proportion of patients with SAD do not receive treatment. Nonetheless, several treatments for SAD are available, and this presentation will discuss the relative merits of different techniques. The findings of meta-analyses and randomised placebo-controlled treatment studies indicate that a range of approaches are efficacious in the acute treatment of SAD. Pharmacological and psychological treatments, when delivered separately, have broadly similar efficacy in acute treatment. It is unlikely that the combination of pharmacological with psychological treatments is associated with greater overall efficacy than with either treatment by itself. Antidepressant drugs with proven efficacy include most selective serotonin re-uptake inhibitors (SSRIs), the serotonin-noradrenaline reuptake inhibitor (SNRI), venlafaxine, the monoamine oxidase inhibitor (MAOI), phenelzine, and the reversible inhibitor of monoamine oxidase A (RIMA), moclobemide; the potential efficacy of tricyclic antidepressants is unknown. Some benzodiazepines and anticonvulsants, and the antipsychotic, olanzapine, also appear efficacious in acute treatment. In the long term, the findings of randomised placebo-controlled relapse-prevention studies in patients who have responded to previous acute treatment reveal a significant advantage for staying on active medication for up to 6 months. Pharmacological treatments are effective not only in reducing symptoms but also in reducing symptom-related disability. Abstract Long-acting injectable antipsychotic treatments (LATs) have traditionally been considered as a "last resort" for those patients with schizophrenia with the most severe or chronic symptoms, non-compliance and frequent hospitalizations. Since atypical long-acting antipsychotics were introduced, it has been more and more appreciated that use of LATs earlier in the disease course can lead to better clinical and functional outcomes by preventing relapses, rehospitalization and deterioration associated with partial or non-adherence. Dr. Andreas Schreiner, J&J EMEA Neuroscience Therapeutic Area Leader, will cover the emerging role of LATs based on recent clinical data & EMEA physicians' clinical experience. Abstract Paliperidone palmitate once-monthly (PP1M), a long-acting injectable antipsychotic treatment (LAT), approved in the United States and numerous other countries has been shown to ensure reliable and sustained exposure and reduce relapse rates among patients suffering from schizophrenia. The recently developed three-monthly injection of paliperidone palmitate (PP3M) has a sustained release formulation, permitting a significantly extended dosing interval, i.e. four doses per year. Dr. Maju Mathews, Global Medical Affairs Leader for Neuroscience at Janssen Pharmaceuticals, will cover the background and history of PP3M development and product information including technology and prescription guidance. Psychiatrists now have the option to offer patients the newest, longest lasting antipsychotic schizophrenia treatment with the simplest dosing regimen (four administrations per year). This will allow time for psychiatrists & patients to discuss and address other important treatment objectives such as patients' life goals, psychosocial treatments and rehabilitation. Abstract In Korea, similar to many other parts of the world, long-acting antipsychotic treatment (LAT) is perceived as a "last option" in schizophrenia treatment. Just recently, patients' access to LATs in Korea has been improved after the government's decision to enhance access in view of the effectiveness of long-acting treatment, making LATs more readily available to patients in need. Dr. Kim Sung Wan, a nationwide key expert in early psychosis management in Korea will present the Korean experience with LATs. Dr Kim will also share the role of the currently evolving Korea community care model developed around the use of long-acting therapy for improving management of schizophrenia. Abstract Our group identified orexin A and orexin B (also known as hypocretin 1 and hypocretin 2) as hypothalamic neuropeptides in 1998. Initially, these peptides were recognized as regulators of feeding behavior. Subsequently, a series of studies suggested that orexin deficiency causes narcolepsy in humans and mammalian species, highlighting roles of this hypothalamic neuropeptide in the regulation of sleep and wakefulness. Studies of efferent and afferent systems of orexin-producing neurons have shown that the orexin neuronal system has close interactions with systems that are involved in the regulations of emotion, energy homeostasis, reward, and arousal. These observations suggest that orexin neurons are involved in sensing the body's external and internal environments, and regulate vigilance states accordingly. I will discuss the neuronal pathways and mechanisms by which the orexin system regulates wakefulness in relation to circadian cycle, emotion, energy homeostasis and other systems. I will also mention about the therapeutic potentials of drugs that target orexin receptors. Abstract Orexin/hypocretin peptides are produced by a cluster of hypothalamic neurons. This small cluster of cells have projections to many brain regions especially those associated with arousal and motivation including the histaminergic neurons of the tubueromammilary nucleus noradrenergic neurons of the locus coeruleus, seretonergic neurons of the raphe nucleus and dopaminergic neurons of the ventral tagmental area. Also, they are responsive to a variety of inputs including the amygdala, nucleus acumbus as well as the dorsomedial nucleus of hypothalamus. Thus, orexin neurons are responsive to stress, autonomic activity, hunger, satiety, reward system sleep wake homeostasis and circadian timing. Effects on sleep wake are well documented, with antagonist improving sleep onset and maintenance effects, while agonists producing sustained wakefulness and reversal of sleep deprivation effects. The improvement in sleep Brexpiprazole as a treatment for schizophrenia Speaker: Christoph Correll, USA Abstract The efficacy and safety of brexpiprazole monotherapy versus placebo have been investigated in two Phase III clinical trials in patients with an acute relapse of schizophrenia. 1,2 The findings of these studies were that, over 6 weeks of The role of cognitive dysfunction in depression and what it means for the patient, clinician and society Abstract Cognitive dysfunction is a core diagnostic symptom for depression according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition and the International Classification of Diseases, 10th Revision. Cognitive dysfunction is common during depressive episodes and may persist into remission,1 with deficits reported in the domains of executive function (including planning and task initiation/monitoring), memory, attention and psychomotor speed.1 Assessment of cognitive dysfunction in patients with depression: which test is best? John Harrison, UK Recently, there has been increased interest in establishing methods for targeting the cognitive deficits observed in patients with major depressive disorder. The use of multiple measures offers the possibility of characterising the effects of therapeutic interventions on cognitive performance.1 However, this approach raises the challenge of how Otsuka Abstract A number of people have depressive disorders, and the socioeconomic loss (suicide, absence from work, etc.) induced by this condition cannot be overlooked. Although the society, including mental health community, has attempted to solve this public problem, a solution has not been found yet. The Japanese Society of Mood Disorders (JSMD) regarded diagnosis and psychiatric management of depression, among other factors, as the key to solve this problem. For example, patients who meet the DSM major depressive disorder (MDD) criteria still have numerous subtypes, and they often have other psychiatric comorbidities that a diagnosis of MDD alone cannot detect. Although the process