Many patients with schizophrenia experience persistent symptoms or side effects on their current antipsychotic regimen. Such patients, particularly those treated with conventional antipsychotic agents may benefit from switching to atypical agents, which offer broader efficacy and improved tolerability compared with earlier counterparts. In addition, patients already receiving treatment with an atypical agent may benefit from switching to an alternative atypical, given that there is great variation in (1) individuals’ response to different atypical antipsychotics, and (2) the side-effect profile of the atypicals. With switching from one antipsychotic to another becoming increasingly common, there is an urgent need to define optimal switching strategies. The main goal when switching antipsychotics is to improve or (in stable patients) maintain the symptomatic and functional level, while improving (or not worsening) tolerability. It is important to identify patients who would be likely to benefit from switching and to discuss with them and their carers the advantages and potential problems of the switching process. To date, four strategies have been effective in controlled studies of switching to atypical antipsychotics: therapeutic dose initiation of the new antipsychotic and abrupt discontinuation of the first (‘abrupt switch’); gradual dose escalation of the new antipsychotic and abrupt discontinuation of the first (‘ascending switch’); therapeutic dose initiation of the new antipsychotic and gradual discontinuation of the first (‘descending switch’), and; gradual dose escalation of the new antipsychotic and gradual discontinuation of the first (‘cross-titration’). An individualized approach is key to the success of switching, as are patient co-operation and carer support.

Combination therapy is well established in bipolar disorder; however, the evidence for this approach in schizophrenia is less robust. Despite the absence of clear guidance, antipsychotic combinations are commonly used in real-life practice, with estimates suggesting that 20–60% of patients receive multiple antipsychotics concurrently. Such polypharmacy may be clinically useful, combining diverse pharmacological actions. However, a clear pharmacological rationale for specific antipsychotic combinations has not yet been elucidated. In this presentation, we consider the varying pharmacological profiles of agents currently used for schizophrenia and explore how best this pharmacology may be exploited to maximize the newer atypicals in clinical practice. For decades schizophrenia has been treated with some success using typical antipsychotics, which are antagonists at dopamine D2 receptors. Atypical antipsychotics were then developed, having D2 antagonism with additional affinity for other receptors, such as serotonin 5-HT2A and 5-HT1A receptors. Most recently, partial D2 agonists have been developed with efficacy to treat schizophrenia and bipolar disorder. These agents have lower intrinsic activity than full agonists, so can act either as functional agonists or antagonists. Additionally, actions to increase noradrenergic function in the prefrontal cortex may be implicated in the efficacy of some antipsychotics. Given the rich pharmacology of antipsychotics, can the combined use of agents with synergistic mechanisms of action provide a true clinical advance in schizophrenia treatment? Polypharmacy is a complex challenge that requires further study in well-designed, randomized, controlled studies. We will review the pharmacological rational for antipsychotic combination therapy and recent clinical evidence for their benefits.

Although the induction of sleep was originally considered to be a desirable therapeutic endpoint for the rapid control of agitation, it is increasingly recognised that sedation is not a prerequisite for acute symptom control. Moreover, excessive sedation or ‘over-sedation’ can interfere with the physician's ability to evaluate the patient and establish an effective therapeutic alliance with them, thus potentially influencing future compliance and treatment outcomes. Over-sedation is also strongly disliked by patients. Thus, achieving control of agitation via rapid calming rather than sedation is becoming an important therapeutic goal. Sedative agents, such as lorazepam, have traditionally been used for the management of acute agitation. However, problems with over-sedation have led to the increased use of intramuscular (IM) antipsychotics – which are easy to administer and provide rapid symptom relief of acute agitation – as a first-line approach in the acute setting. The recent availability of atypical antipsychotics as IM formulations represents a significant step towards meeting the goal of efficacy without over-sedation. Aripiprazole, olanzapine and ziprasidone have demonstrated efficacy in the management of acutely agitated patients with schizophrenia. Indeed, IM aripiprazole has been shown to be equally effective as IM haloperidol with a lower risk of extrapyramidal symptoms. Importantly, calming of acutely agitated patients without excessive sedation is emerging as a significant clinical advantage of IM atypicals over older treatments such as typical antipsychotics or benzodiazepines. Thus, physicians should consider the specific, sedation-independent calming effects of atypicals.

The investigation of the comparative efficacy of the combination of pharmacotherapy and psychotherapy versus either modality alone has to consider several methodological issues. Neglect of these methodological aspects can lead to severe pitfalls. Also, the interpretation of the results of such studies should be performed very carefully, considering several aspects. Among others, the following questions have to be addressed:

• – Was the study performed in a more psychopharmacology-oriented or more psychotherapeutically-oriented institution?

• – Were the patients acutely or chronically ill?

• – Were the patients already refractory to pharmacotherapy or psychotherapy prior to inclusion in the study?

• – Was the pharmacotherapy performed according to the state of the art?

• – Was the psychotherapy performed according to the state of the art?

• – Was the pharmacotherapy administered under double-blind conditions, using a placebo control or another kind of control?

• – Was the psychotherapy administered in the context of a pseudo placebo control group?

• – Was the sample size adequate for a confirmative trial?

Generally it has to be taken into consideration that it is much more difficult to prove efficacy of a combination therapy versus an active mono-therapy then to prove efficacy of a mono-therapy or combination therapy versus placebo. Overall, there seems to be evidence for superior efficacy of the combination of antidepressants with cognitive behaviour therapy, especially in certain subgroups of patients.

There is now a large body of controlled trial research into the efficacy of psychological treatments in unipolar affective disorder, indicating their place in acute treatment and in prevention of relapse and recurrence. In bipolar disorder the evidence is still less strong, but studies are rapidly accumulating. Psychological treatments have been almost always combined with medication. The psychological approaches have included psychoeducation, cognitive therapy (CBT), interpersonal and social rhythm therapy (IPSRT), family therapy. Some approaches have used mixtures of elements, particularly psychoeducation with family or cognitive therapy. Benefits found have included symptom improvement, improvement in social function, relapse prevention and improved adherence to drug regimes. However findings have not been entirely consistent, so that definitive recommendations are still premature. Effects may be weaker than in unipolar disorder. In contrast to unipolar disorder, where the strongest body of empirical evidence favours cognitive therapy for symptom remission and relapse prevention, in bipolar disorder psychoeducationally-based approaches may emerge to be of greater benefit.

How do social networks add value for the work of leaders? What are key network mechanisms? How can you improve the strategic impact of your social capital? This session introduces the idea of ‘social capital’, along with social network concepts, tools, and strategies. The evidence comes from recent findings about how collaboration in basic research in biotechnology occurs, how firms explore innovative technologies, and on how individuals create professional advantage. The themes focus on how social networks change the terms of value creation, create de facto systems of opportunity and advantage, and extend basic leadership in contested, ambiguous professional settings. The session is interactive, rather than one-way lecture.

Read aheads for the session

• – Hargadon, A. 2006. ‘Brokers of innovation.’ Focus, vol. VIII, no. 1.

• – Uzzi, B and S Dunlap. 2005. ‘How to build your network.’ HBR, December.

• – Reprint # R0512B

• – Weick, K. 1996. ‘Prepare your organization to fight fires’ HBR, May-June.

Half of the world's population are children or adolescents. Nearly 5% of them suffer from mental disorders and another five percent have conduct disorders.

Even in highly developed industrialized countries mental disorders in this age are often not recognized nor taken seriously. The situation is made worse by the lack of awareness of the magnitude and severity of the problems caused by mental disorders of children and adolescents by political and health decision-makers, by health professionals and by the general public; and by the fact that health professionals and others involved in child care and development have often only rudimentary knowledge about appropriate methods of prevention and treatment of mental and neurological disorders in childhood and adolescence.

It is for this reason that the World Psychiatric Association (WPA) carried out in collaboration with the World Health Organization (WHO) and the International Association for Child and Adolescent Psychiatry and Allied Professions (IACAPAP) this unprecedented program.

This program aims at; increasing the awareness of health decision-makers,health professionals and the general public about the magnitude and severity of problems related to mental disorders in childhood and adolescence and about possibilities for their resolution; at promoting the application of measures of primary prevention of mental disorders in childhood and adolescence and of interventions that will contribute to the healthy mental development of children and adolescents; and support to the development of services for children and adolescents with mental disorders and to facilitate the use of effective methods of treatment.

In Sweden, CAP (Child and Adolescent Psychiatry) has a history of more than 100 years. The discipline developed out of paediatrics, education, child social welfare and psychiatry in that time order. In similarity to the situation in Switzerland, “school -psychiatry” was established as a branch of CAP with the aim to understand the link between cognition, behaviour and health and to promote health for children with slow learning capacity and mental retardation who in those days were children at a high risk for juvenile delinquency. The first CAP units opened at the end of World War I in the Stockholm Public School system and at the Paediatric Clinic of Norrtull's Children's Hospital, one of the two Paediatric University Clinics at the Karolinska Instituted in Stockholm. From 1920-1970, school psychiatry was an important part of child and adolescent work in Sweden. It was based on a true cooperation between CAP and Education using the principles from “heilpädagogie” i.e. “curative education”: as follows:

To support pupils’ creativity, language and speech competence and their social competence

To accept each pupil's individual maturity/developmental level and behavior by introducing “School-maturity tests” before school-start.

To introduce different school curricula for children with average intelligence, school-immaturity, slow learning capacity (IQ 70-90), mental retardation etc.

To introduce special training for teachers in order to have teachers that knew how children with “problems” should be taught.

To use screening and monitoring of skills i.e. screening of intellectual skill, language, reading, spelling, math's, maturity, behavior, health at preschool start,

Suicide among young people age 15 – 24 constitutes a considerable burden on the global level. Data from 90 out of the 130 WHO members states show that suicide was the fourth leading cause among young males and the third for young females. Suicide rate is higher in young males (world average 10.5 per 100 000) than in young females (world average 4.1 per 100 000). A rising trend of suicide in young males is observed in many countries and particularly marked on other continents than Europe.

Since suicide risk is high among psychiatrically ill young people. Therefore, an adequate treatment of psychiatric disorders and improved detection of psychiatric illnesses in the general population is important. Preventive measures in the health care services after a suicide attempt and an early recognition of children and young people at risk in schools by screening, gate keepers training and other awareness programs are essential strategies.

The results of those studies as well as the worldwide initiative launched by the WHO in SUPRE for the prevention of suicide, will be presented.

Previous studies have shown that most patients in forensic services are men with schizophrenic disorders who have a long history of treatment in general psychiatry, during which time they were committing crimes and engaging in aggressive behaviour. The present study was designed to examine violent behaviour among severely mentally ill (SMI) patients in general psychiatry and the treatments that they received. A representative sample of 220 inpatients with SMI in an urban area in the UK was examined. The prevalence of at least one conviction for a violent crime (46.7% of the men,16.5% of the women) was higher among the patients than among an age and gender matched cohort of the UK population. The elevations in risk for violent offending by patients with SMI compared to the general population were similar to those observed previously in other countries. In the six months prior to interview, 49.2% of the men and 38.8% of the women engaged in physical aggression towards others, and one-in-five engaged in serious violence. Two years later, 79% of the patients were re-assessed. All patients had been receiving antipsychotic medications and meeting with their care co-ordinators (nurses, social workers), on average, once a week, but only 6 patients received treatments relating to substance misuse and 2 patients participated in an anger management programme. More than 80% of the patients experienced at least two negative outcomes defined as high symptom levels, aggressive behaviour, substance misuse, and physical victimisation. General psychiatric services did not address patients’ problems with violence.

The prejudice of the outstanding dangerousness of individuals with severe mental illness is one of the major reasons for the special position of psychiatry among the several medical disciplines. The mental health reforms initiated during the second half of the 20th century had the principal aim to move the locus of treatment and care from the big mental hospitals into the community and to strengthen the patients’ civil rights - so reducing stigmatization and ‘normalizing’ the aforementioned special position of psychiatry. Despite all doubtless improvements for the majority of mental patients every European country is reporting on rapidly growing admission rates of mentally ill offenders to forensic hospitals. A possible association with the introduction of mental health reforms is under continuous discussion.

It will be shown that not single details of the reforms but, rather, the changed attitude towards a subgroup of severely mentally ill subjects being at higher risk of violence could be the crucial issue. These patients hamper the desired ‘normalization’ of the position of psychiatry, and, in fact, modern community care hardly offers sufficient treatment options for them.

The basis for this development may lie in the societal changes of the last decades. Today, we do dispose of the ‘technical’ (financial, pharmacological) preconditions for the treatment of severely mentally ill patients. However, the emotional preconditions of society and its representatives seem to be only insufficiently developed. Therefore, forensic hospitals are in danger to take over the role of the old psychiatric asylums.

Coronary artery bypass grafting (CABG) is a worldwide used myocardial revascularization procedure, which despite the modern advantages still has a spectrum of complications, especially in old age population.

The relatively old age of the patients who undergo CABG and their widespread atherosclerotic disease are possible reasons for vascular sequels leading to neurological and psychic dysfunctions. Delirium in the elderly after CABG surgery is common, according to some authors and our investigation, is detected in about 20- 34% causes and is often under-diagnosed. Its occurrence may be predisposed by a history a stroke and precipitated by a longer duration of cardiopulmonary bypass.

Increasing age, blood urea level, cardio-thoracic index, hypertension, smoking habits, blood replacement during bypass, atrial fibrillation(AF), pneumonia and blood balance in the post-operative period are the main risk factors for delirium. No specific factor associated with the CABG (eg. perfusion pressure, number of grafts) is correlated with increased risk for delirium post-operatively.

The number of studies (and our observations) have shown that patients in whom delirium develop have more complication rates, longer hospital stays, an increased rates of transfer to rehabilitation or long –term care facilties.

Finally, the identification and control of the risk factors for delirium should bring a decrease in delirium morbidity and mortality.

Suicide rates in elderly people have been high, worldwide. Suicide in elderly people is multifactorial. Mood disorders, physical illnesses, and previous suicide attempt, has been associated with increased risk of suicide in elderly people. Delirium or acute confusional state, also, has been proposed as a risk factor. Delirium is characterized by a disturbance in consciousness, change in cognition, perceptual disturbances, and often has multiple underlying causes. Delirium is often undetected or misdiagnosed, and is difficult to evaluate suicidal thoughts and intent in delirious patients. There is a debate in the medical literature concerning the role of delirium as a risk factor of suicidal behaviour. It has been proposed that, confusional state contribute to impulsive suicide attempts, as could occur, in cancer or in AIDS patients. However, past work suggested that delirium was a protective factor for suicide.

Cocaine produces its psychoactive effects primarily by blocking presynaptic transporters for biogenic amine neurotransmitters, especially dopamine and serotonin. This has the effect of increasing activity in the brain's mesocorticolimbic dopaminergic reward circuit. There is no proven medication to treat cocaine dependence. The difficulty in developing an effective medication may derive from cocaine's direct activation of the reward circuit, its ability to generate sensitization with repeated use, and its rapid access to the brain when smoked or injected. Attempts to directly affect the reward circuit, e.g., by blocking the dopamine transporter or dopamine receptors, have not been successful. Attempts to indirectly influence the reward circuit by affecting other neurotransmitters that modulate it have been more promising. These include increasing activity of GABA (an inhibitory neurotransmitter) with baclofen, vigabatrin, or topiramate (which also decreases glutamate activity); and increasing the activity of glutamate (an excitatory neurotransmitter) with N-acetylcysteine. Also somewhat promising are agonist substitution approaches using long-acting amphetamine preparations. Medications that are promising in animal studies, but not yet tested in humans, include dopamine D3 receptor partial agonists and cannabinoid CB1 receptor antagonists. In addition to these pharmacodynamic approaches, pharmacokinetic approaches, which reduce cocaine's access to the brain or enhance its metabolism, are being studied. An anti-cocaine vaccine, which binds cocaine and keeps it from crossing the blood-brain barrier, has been safe and effective in early clinical trials. Administration of cocaine-metabolizing enzymes, e.g., butyrylcholinesterase, has been effective in animal studies, but not yet studied in humans.

Although no pharmacological treatment has proved to be highly effective for reducing cocaine dependence, several medications have been tested over the last decade and have shown promising efficacy. Modafinil (Provigil), known as a treatment for day time sleepiness, and Topiramate (Topamax), an anti-epileptic medication also prescribed for migraine, have been shown to be effective in controlled clinical trials. We have recently started a major study utilizing Positron Emission Tomography (PET) brain imaging to monitor the progress of pharmacotherapy with modafinil or topiramate in cocaine-dependent and methadone-maintained cocaine-dependent patients. Patients will be assessed before treatment, and again after 4 weeks of pharmacotherapy. The aims of the project are to study effects of the two medications on cocaine dependence and craving, and on dopamine binding in the brain. At each assessment session, patients will undergo PET with [11C] raclopride to image the dopamine receptor DRD2. To trigger craving, patients will then be exposed to a videotape showing cocaine use; a questionnaire will be used to record their subjective responses, and a second PET scan will be performed with [18F] fluorodeoxyglucose (FDG) to image cerebral glucose metabolism during craving. This protocol was designed to enable us to study changes resulting from pharmacotherapy on dopamine binding in the brain, and on craving as reflected both in subjective measures and regional cerebral glucose metabolism. In addition, we will investigate the association between subjective measures of craving for cocaine and the level of dopamine DRD2 receptor occupancy in the brain before and after treatment. Notwithstanding the complexity of the clinical and therapeutic reality characterizing cocaine dependence, we hope to present preliminary evidence for the relative efficacy of these two promising medications in treatment for cocaine. dependence. This evidence could also elucidate the brain mechanisms underlying cocaine craving and dependence in cocaine-dependent patients.

The development of medications for the treatment of cocaine dependence has been a high priority of the U.S. National Institute on Drug Abuse, National Institutes of Health. One of the main strategies has been to test available, marketed medications that affect CNS function and have a rationale for testing in a cocaine dependent population. The Cocaine Rapid Evaluation Screening Trials (CREST) utilized a randomized, controlled, parallel group, blinded methodology for comparing one or more medications against a placebo. Subjects were evaluated for a 2-4 week baseline and then randomized to a treatment group for 8 weeks. Standardized measures of outcome were used: urinary benzoylecgonine, retention, craving, depression, clinical global impressions, HIV risk behaviors. Counseling and procedures were also standardized across studies to facilitate data comparisons across drug classes. A total of 19 drugs were evaluated in 5 research clinics. Results from the studies suggested that cabergoline and reserpine should be further evaluated. Less robust effects were seen with sertraline and tiagabine although the sample size in each group was small (n= 15/group). Trials were analyzed separately and then a pooled analysis was performed. For example, an analysis of characteristics leading to at least 2 weeks of abstinence was performed. Being female with at most 5 years of prior use and being over 40, being a non-African-American male with at least four baseline uses and more than 4 years of prior use, and males with at most three baseline uses and less than 20 years of prior use were associated with abstinence rates of 25, 30, and 42 %, respectively. One of the lessons learned was the potential value of assessing cocaine use during the baseline period prior to randomization. Another lesson learned was the use of both standardized assessments across sites and outcome measures that were also employed within individual sites. This allowed exploratory analyses within sites to determine sensitivity of outcome measures.