In her talk, Sigrid will focus on a number of aspects that arise as a consequence of an individual's diagnosis as suffering from a severe mental disorder, such as schizophrenia, and particularly how a diagnosis affects the wider family unit.

From the wider family perspective, the onset of any mental illness is very traumatic and frightening, resulting in total confusion, angst and upset for all members - the sufferer, parents and siblings. So when a diagnosis is finally made, a sense of relief prevails but soon this relief changes when a person realises the real impact of such a diagnosis - in other words, the longer term effects and changes which they will face. A lifetime sentence looms for many.

There is a critical need for information to help understand the illness, support and education to help develop one's coping skills, to name just a few issues. Also, a very negative result of someone being diagnosed as suffering with a mental illness is the onset of feelings of stigmatisation, discrimination and isolation. Sigrid will deal with these topics and will explore the efforts which EUFAMI has been employing to counter these.

Individuals diagnosed with borderline personality disorder usually seek for treatment as adolescents or young adults. As age progresses, longitudinal studies suggest that borderline patients improve psychosocially, suggesting that they may somewhat belatedly achieve the milestones of young adulthood. Affect regulation may be particularly subject to major changes in young adulthood, as the prefrontal brain areas involved in affective processing underlie maturation processes up into the late third decade. From studies in healthy volunteers we know that that the capacity to process positive affects improves with age. Young adults with borderline personality disorder, however, display a negativity bias in emotion recognition and they have difficulties in inhibiting the recall of negative information. Neuroimaging data suggest that they suffer from deficient implicit affect regulation but they are able to profit from explicit strategies to suppress negative emotions, an observation which could have interesting implications for treatment. Regarding future research more efforts on developmental psychopathology on the one hand, brain maturation on the other will help to further understand the nature of borderline personality disorder. Regarding clinical issues early treatment designed to foster affect regulating competencies and self-esteem and to develop interpersonal skills might benefit young patients diagnosed with borderline personality disorder.

In adult psychiatry early recognition and treatment of schizophrenia has become a major goal because of manifold evidence of a relation between delayed initiation of treatment and an unfavourable developmental course. The duration of untreated psychosis (DUP) seems to be significantly prolonged in adolescents compared to adults due to both a protracted sub-threshold development of psychotic features and the failure of families and health professionals to take seriously the initial signs of psychosis that mimic quasi normal adolescent emotional perturbations. Although in adults studies have shown a subset of prodromal signs and attenuated psychotic features to have predictive evidence for the development of schizophrenia, these symptoms however seem of limited specificity in adolescence. Basic symptoms represent subjective experiences of the prodromal phase and will be presented in a sample of schizophrenic adolescents in comparison to non-psychotic patients and normal controls. Results reveal that basic symptoms do not show any specificity for schizophrenia, but schizophrenics present with higher amounts of basic symptoms in the prodromal phase compared to non-psychotic controls. For early recognition a combination of psychopathological and biological markers seems fruitful. First data on perceptual closure and event related potentials of the optic system will be presented that seem to differentiate between early and late onset schizophrenia.

Suicide is one of the leading causes of mortality among adolescent suicides. Data from the WHO European Multicentre study on attempted suicide indicates that rates of attempted suicide and suicide in the young co-vary. The association is strongest and significant for male adolescents and young adults. Furthermore, recent studies have reported a shift to suicide methods with higher lethality for both genders.

Suicide prevention strategies are directed at the general population and health care services. Suicide risk is high among adolescents with psychiatric illness, so adequate treatment and detection of psychiatric illnesses in young people is essential. Preventive measures in health care services after a suicide attempt and early recognition of young people at risk in schools are also essential strategies.

The emphasis of suicide prevention work needs to shift to an earlier stage of the suicidal process. This question is addressed by the global suicide prevention initiative SUPRE (SUicide PREvention), in the WHO publication Preventing suicide: a resource for teachers and other school staff, which can be adapted to local conditions and inserted in syllabuses for training both pupils and staff.

An intervention project called SAYLE: Saving Young lives in Europe is funded by the EU for adolescents in European schools over 12 EU countries. Its main objectives are to lead adolescents to better health through decreased risk taking and suicidal behaviours. Outcomes of preventive programs will be evaluated and culturally adjusted models for promoting health of adolescents in different European countries are planned to be developed.

Epidemiological data indicate that about one third of all pregnant women receive at least one psychotropic drug (Goldberg & Nissim 1994). Women with mental disorders bear a considerable risk of relapse when psychotropic medication is discontinued during pregnancy and the postpartal period.

TDM aims to better individualize dosing regimens taking into account relevant pregnancy-induced metabolism returning to baseline activities within 24 hours (Adab 2006).

Despite the frequent use of psychotropic drugs in pregnancy, for several psychotropic drugs only few documented cases regarding their influence on organogenesis, delivery complications or long term effects are available. Therefore, one should follow some general guidelines when treating pregnant women (cf. Bergemann & Conca). Furthermore, it is recommended to guide any psychopharmacological therapy by TDM. TDM in pregnant women and/or mothers is recommended to be carried out at least once per trimester and within 24 hours after delivery. For TDM at delivery umbilical cord blood of neonates exposed in utero to psychotropic drugs should be collected, since possible neonatal symptoms has to be differentiated from a withdrawal syndrome versus toxic effects of the substances (cf. Koren 2006, Pakalapati et al. 2006).

The use of psychotropic medications during breast-feeding has some implications. All psychotropic medications enter breast milk. However, current data do not support monitoring breast milk levels in attempt to estimate individual infant plasma levels, since the effective drug concentration in the neonate is essentially determined by its own metabolism (Weissman et al. 2004). A systematic monitoring of mother and child including TDM is recommended.

More than 80% of all adverse drug reactions are Type A reactions and dependent on drug concentrations. Therapeutic Drug Monitoring (TDM), Drug Interaction checking programs and pharmacogenetic tests are valuable instruments in elucidating or preventing Type A reactions. It stands for Quality Assurance in clinical practice. The TDMplus algorithm (Jaquenoud Sirot E et al 2006) is helpful in clinical practice and prevents unnecessary testing. This decision tree leads in several “stop/go” steps from the clinical situation of inefficacy or adverse reaction to measuring and interpreting plasma levels, checking for pharmacokinetic interactions and finally, if indicated, to pharmacogenetic tests with gentoyping and/or phenotyping. Genetic results are noted on a personal “pharmacogenetic card” for the patient's future treatments.

The interplay of genetics, drug interactions, life style and other personal vulnerabilities like comorbidity make prediction of drug response very complex. The use of TDMplus has proven useful guiding the clinicians in difficult clinical situations and helping elucidating the causality of adverse drug reactions. Its practical benefit has been shown with pharmacovigilance cases from the AMSP program (Arzneimittelsicherheit in der Psychiatrie = Drug Safety in Psychiatry).

Evidence has been given that antipsychotic effects of dopamine receptor antagonists are associated with 60 and 80% striatal dopamine D2 and D3 receptor occupancy. Receptor occupancy correlates well with concentrations of the antipsychotic drugs in serum or plasma, much better than the dose. The latter is consistent with weak correlations between antipsychotic dose and serum concentrations and explained by the high interindividual variabilities in drug metabolism. Using positron emission tomography (PET) for in vivo determination of dopamine receptor occupancy in conjunction with drug concentration measurements “therapeutic windows” could be calculated for the atypical antipsychotic drugs amisulpride, risperidone and ziprasidone. On the other hand, analysis of drug concentrations in serum of schizophrenic patients who were treated with these drugs and who had responded to the medication confirmed the PET derived target levels and with some modifications also those of aripiprazole and clozapine. In vivo characterisation of dopamine receptor occupancy and measurement of blood levels should therefore be part of the clinical trials during the development of new antipsychotic drugs. They provide most relevant information for the later use of therapeutic drug monitoring to optimise the treatment of individual patients.

A dose related reference range is calculated as a concentration range within that a drug concentration has to be expected in human blood specimens under medication with a given dose of the drug. The calculation is based on the direct correlation of the drug dose De (constant dose under long term therapy) to its blood concentration c with the total clearance of the drug (Clt) being the correlation coefficient (De = D / t = c × Clt). The clearance is taken as arithmetic mean ± standard deviation from phase II clinical trials of the drug. Thus the dose related reference range will statistically contain 68,27 % of all the drug concentrations determined under normal condition in the blood of a normal patient, where “normal” is defined as the patient population in the respective phase II clinical trial. It usually consists of patients 18-65 years of age without relevant comorbidity, comedication, and genetic abnormalities in drug metabolism. Therefore, any drug concentration determined outside its dose-related reference range creates a signal to alert for individual abnormalities in a patient such as drug-drug-interactions, gene polymorphisms that give rise to slow/rapid metabolizers, altered function of the excretion organs liver and kidneys by age and/or disease, compliance problems, a missing pharmacokinetic steady state and even signal overlay in the laboratory analysis. A table listing factors that allows the calculation of dose-related reference ranges for all relevant psychopharmaca will be included in the first update of the TDM consensus guideline to be published in Pharmacopsychiatry.

Movement disorders in psychiatry can be divided in those related to an underlying neurological or other somatic disease, related to a psychiatric syndrome, drug induced and psychogenic. In this workshop the typical clinical aspects of each of these movement disorders will be discussed and shown on video with the focus on drug induced. Drug induced can be divided in acute and tardive movement disorders. Acute movement disorders such as acute dystonia, akathisia, parkinsonism and mycoclonus, start short after taking dopamine receptor blocking agents, often an antipsychotic. Once recognized they are relatively easy to treat. Tardive movement disorders such as tardive dyskinesia and tardive dystonia start months or years after using dopamine receptor blocking agents. Treatment is often disappointing, therefore prevention is needed.

Patients with movement disorders do not always complain about their ‘troubles with muscles’ spontaneously, and sometimes, often out of shame, they try to hide their involuntary movements. E.g. a hand tremor can be temporarily suppressed by pushing the hand against the body or sitting on it. To reveal these movement disorders, a systematic investigation of the patient is required. This investigation consists of a (hetero) anamnesis and a physical examination. The anamnesis demands knowledge of sensitive questions such as: ‘Do you notice any movements that are not under your control? Do you feel restless: an inability to keep the legs still? Do you tremble, are you slower than usual?’ Next, a physical examination is required. The investigator lets the patient execute several movements such as stretching the arms, opening the mouth and walking.

In this workshop you will learn and practice this highly sensitive examination. In clinical practice this investigation takes less than 5 minutes and will reveal all drug induced movement disorders.

Hypomania is perhaps the most difficult psychiatric syndrome to rule out retrospectively. However, the retrospective detection of hypomania is crucial for a correct diagnosis of bipolar disorder, and particularly bipolar II, and for the implementation of the right pharmacological treatment. Unfortunatelly, still nowadays, the misdiagnosis of bipolar II disorder as unipolar depression is very frequent, and may carry serious consequences for the patients. The availability of a good screening tool for past hypomania episodes would be extremely helpful.

The psychometric study of the development of the HCL-32 scale in Spain exhibits high internal consistency and similar stability over time, in comparison with other instruments such as the MDQ and suggests that this scale may be very useful for the detection of bipolar disorder and past hypomania.

The results of our study suggest the usefulness of the HCL-32 to screen out previous hypomanic symptoms in psychiatric patients, thus leading to better detection results than with the MDQ, although with the possibility of obtaining more false positives. HCL-32 has been shown to be a useful instrument for the detection of hypomania in patients with an affective disorder. The Spanish version exhibits good psychometric properties in relation to sensitivity and specificity. Given the difficulties involved in both the retrospective and cross-sectional diagnosis of hypomania, a key aspect of appropriate management of bipolar disorders, this questionnaire represents a potential improvement in clinicians’ ability to detect and correctly treat bipolar disorder, and in some aspects such as internal consistency, obtains better results than the MDQ.

The Polish TRES-DEP study assesses a number of demographic, clinical and psychometric features comparing patients with treatment-resistant and treatment non-resistant depression. The study included 1083 patients with single or recurrent depressive episode among which 570 met the criteria for treatment-resistant depression, on account of lack of significant improvement following at least two adequate courses of antidepressant treatment. All 1083 patients were assessed by means of the Polish version of Hypomania Check List 32 Scale. The Cronbach's alpha for entire scale was 0.94 which indicates high degree of consistency. Exploratory factor analysis resulted in five factors, of which the biggest (mostly overactivity and elation) containing items1-6, 7-19, 21, 23 and 27 had eigenvalue 10.95 and accounted for 34.2% and the second (irritability), items 25-26, with eigenvalue 2.92, accounted for 9.1% of total variation. Significant differences were obtained between patients with treatment-resistant and treatment non-resistant depression as to the scores of HCL-32. The mean score of HCL-32 was significantly higher in treatment-resistant vs non-resistant depression (11.9±8.3 vs 8.8±7.7, respectively, p< 0.001). Also, the percentage of patients having positive response to 14 or more items of the scale was significantly higher in treatment-resistant than in non-resistant depression (44% vs 29%, respectively, p< 0.001). Based on the results of HCL-32 scale, it may be concluded that the features of bipolarity make the patient more resistant to antidepressant treatment.

In 1970 antipsychotics (haloperidol, levomepromazine, thiothixene) were recommended in Sweden as 1st line treatment of anxiety in organic brain syndromes, psychoasthenia, and substance abuse. The benzodiazepines came to dominate treatment of anxious patients in the 1970s and are still appreciated for their rapid anxiolytic effect, low clinical toxicity and low price. Evidence-based guidelines, however, recommend the SSRIs, venlafaxine, and pregabalin as first line treatment in anxiety disorders.

Studies are currently ongoing to assess the utility of new antipsychotics in primary anxiety disorders: quetiapine, risperidone, aripiprazole, ziprazidone, and olanzapine. This is justified in the light of that a large proportion of these patients, about 1/3, do not respond to 1st line treatments or discontinue due to adverse drug effects. Augmentation therapy with antipsychotics may enhance response rates. Primary anxiety disorders may include psychotic symptoms such as dissociation, or severe insomnia, that may be targeted with these medications.

Another important patient category are patients with substance use disorders, particularly alcohol, in whom there are few or no controlled studies of conventional anxiolytics. Anxiety is also common among patients with psychoses, bipolar disorder, ADHD or borderline personality disorder, and few controlled studies have addressed that issue.

Emerging reports indicate that new antipsychotics may be useful as 1st line therapy, as augmenters, and in patients with anxiety due to psychoses and bipolar disorder. In this educational update, the results regarding symptoms, adverse effects, and functioning of these recent studies will be discussed.

There are actually four types of situations where intervention with antipsychotics might be considered for the treatment of Obsessive compulsive disorder. Obsessive compulsive patients with poor insight (what was previously called ‘psychotic obsession’), schizophrenic patients with OCD, obsessive compulsive patients with tic disorder, and obsessive compulsive patients who did not respond to intervention with an adequate treatment of antiobsessive medication.

The data supporting the role of antipsychotic medication in obsessive compulsives with poor insight are not convincing. However, at times the treatment dilemma (antipsychotic or antiobsessive) actually derives from diagnostic ambiguity; many of the very severe ego-syntonic obsessive compulsive patients may be erroneously diagnosed as schizophrenic, while they are actually severe OCD that should be treated with antiobsessive medication and not antipsychotic.

The prevalence of OCD amongst schizophrenic patients ranges from 10-25% and has a negative effect on the prognosis for those substantial proportion of schizophrenic patients. Preliminary data implies that for this subset of patient (the schizo-obsessive patients) a combination of antipsychotic and antiobsessive medication might be useful.

It is crucial to screen for tic disorder in patients with, OCD as this subset of patients responds (both in terms of obsession and tics) to a combination of typical antipsychotic and antiobsessive medication.

Data in regard to augmentation of OCD patients who did not respond to treatment with SSRI suggest that risperidone might have a specific therapeutic potential in this subset of patients. The role of antipsychotics with 5HT1D properties like ziprasidone need to be studied.