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BackgroundSelf-ratings of psychotic experiences might be biased by depressive symptoms.MethodData from a large naturalistic multicentre trial on depressed inpatients (n = 488) who were assessed on a biweekly basis until discharge were analyzed. Self-rated psychotic symptoms as assessed with the 90-Item Symptom Checklist (SCL-90) were correlated with the SCL-90 total score, the SCL-90 depression score, the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale 21 item (HAMD-21) total score, the Montgomery Åsberg Depression Rating Scale (MADRS) total score and the clinician-rated paranoid-hallucinatory score of the Association for Methodology and Documentation in Psychiatry (AMDP) scale.ResultsAt discharge the SCL-90 psychosis score correlated highest with the SCL-90 depression score (0.78, PPPPPPPP = 0.02).ConclusionsIn depressed patients self-rated psychotic symptoms correlate poorly with clinician-rated psychotic symptoms. Caution is warranted when interpreting results from epidemiological surveys using self-rated psychotic symptom questionnaires as indicators of psychotic symptoms. Depressive symptoms which are highly prevalent in the general population might influence such self-ratings.

BackgroundTo analyse insight of illness during the course of inpatient treatment, and to identify influencing factors and predictors of insight.MethodsInsight into illness was examined in 399 patients using the item G12 of the Positive and Negative Syndrome Scale (“lack of insight and judgement”). Ratings of the PANSS, HAMD, UKU, GAF, SOFAS, SWN-K and Kemp's compliance scale were performed and examined regarding their potential association with insight. The item G12 was kept as an ordinal variable to compare insight between subgroups of patients.ResultsAlmost 70% of patients had deficits in their insight into illness at admission. A significant improvement of impairments of insight during the treatment (pp = 0.0004), less suicidality (p = 0.0218), suffering from multiple illness-episodes (pp = 0.0012) at admission were identified to be significant predictors of poor insight at discharge.ConclusionThe revealed predictors might function as treatment targets in order to improve insight and with it outcome of schizophrenia.

This position statement will address in an evidence-based approach some of the important issues and controversies of current drug treatment of depression such as the efficacy of antidepressants, their effect on suicidality and their place in a complex psychiatric treatment strategy including psychotherapy. The efficacy of antidepressants is clinically relevant. The highest effect size was demonstrated for severe depression. Based on responder rates and based on double-blind placebo-controlled studies, the number needed to treat (NNT) is 5–7 for acute treatment and four for maintenance treatment. Monotherapy with one drug is often not sufficient and has to be followed by other antidepressants or by comedication/augmentation therapy approaches. Generally, antidepressants reduce suicidality, but under special conditions like young age or personality disorder, they can also increase suicidality. However, under the conditions of good clinical practice, the risk–benefit relationship of treatment with antidepressants can be judged as favourable also in this respect. The capacity of psychiatrists to individualise and optimise treatment decisions in terms of ‘the right drug/treatment for the right patient’ is still restricted since currently there are no sufficient powerful clinical or biological predictors which could help to achieve this goal. There is hope that in future pharmacogenetics will contribute significantly to a personalised treatment. With regard to plasma concentration, therapeutic drug monitoring (TDM) is a useful tool to optimize plasma levels therapeutic outcome. The ideal that all steps of clinical decision-making can be based on the strict rules of evidence-based medicine is far away from reality. Clinical experience so far still has a great impact.

Tobacco dependence is the most common substance use disorder in adults with mental illness. The prevalence rates for tobacco dependence are two to four times higher in these patients than in the general population. Smoking has a strong, negative influence on the life expectancy and quality of life of mental health patients, and remains the leading preventable cause of death in this group. Despite these statistics, in some countries smokers with mental illness are disadvantaged in receiving intervention and support for their tobacco dependence, which is often overlooked or even tolerated. This statement from the European Psychiatric Association (EPA) systematically reviews the current evidence on tobacco dependence and withdrawal in patients with mental illness and their treatment. It provides seven recommendations for the core components of diagnostics and treatment in this patient group. These recommendations concern: (1) the recording process, (2) the timing of the intervention, (3) counselling specificities, (4) proposed treatments, (5) frequency of contact after stopping, (6) follow-up visits and (7) relapse prevention. They aim to help clinicians improve the care, health and well being of patients suffering from mental illness.Disclosure of interestIn the last three years, HJM received honoraria for lectures or for advisory activities by the following pharmaceutical companies: Lilly, Lundbeck, Servier, Schwabe and Bayer.He was president or in the Executive Board of the following organisations: CINP, ECNP, WFSBP, EPA and chairman of the WPA-section on Pharmacopsychiatry.

Relapse is one of the key factors in the long-term outcome of schizophrenia. The consequences of relapse are diverse and often unpredictable, and the time to recovery and degree of recovery worsen with each successive relapse. There is now overwhelming evidence that advances in antipsychotic drug treatment have led to significant reductions in the rate of relapse. This review charts the developments that have taken place in antipsychotic therapy from the introduction of depot formulations, through atypical agents, to the development of the first long-acting atypical antipsychotic. Depot formulations of conventional antipsychotics were developed in the 1960s and led to fewer relapses and episodes of hospitalization, compared with oral equivalents. Meta-analysis has confirmed that patients receiving depot antipsychotics experience significantly greater global improvement than those receiving the respective oral agents. Conventional antipsychotics are, however, associated with a range of potentially serious adverse events. The atypical antipsychotics were introduced in the 1990s and have significant advantages over conventional agents with regard to positive and negative symptoms. There is also evidence that atypical agents can reduce the risk of relapse. Importantly, atypical antipsychotics have an improved safety profile compared with older agents, particularly with regard to extrapyramidal symptoms. One disadvantage of atypical agents has been that they are only available in an oral form. The recent development of a long-acting injectable formulation of risperidone means that a new treatment option is available to physicians.

Evidence based medicine is a cornerstone of modern medicine including psychiatry. Treatment practice guidelines are nowadays available for guiding mental health care mainly with a focus on specific disorders. Many important clinical situations or problems beyond treatment, however, are lacking proper guidance. It is in this scope that a European Psychiatry Association (EPA) has developed its own program, the European Guidance Project. The present special issue presents six topics out of these series of guidance documents.

SummaryIs the onset of efficacy of antidepressants always delayed and which early clinical signs predict final outcome of therapy ? Our analyses show that strict response criteria produce necessarily later onset estimations rather than less strict ones. In two large-scale clinical samples we compared different estimation methods of the day of onset. Patients' direct ratings produced the earliest onset estimations. Because of the strong dependency of onset estimations on measurement methods, we argue that it is still open to debate, in which degree drug response is delayed. Concerning early clinical signs of final outcome we compared early changes of the Hamilton Rating Scale for Depression (HAM-D) items with several measures of final outcome. From the data we analyzed, there are no sufficiently precise signs of final outcome within the first 2 weeks of therapy.

The negative image of psychiatry is not only due to unfavourable communication with the media, but is basically a problem of self-conceptualization. It results both from unjustified prejudices of the general public, mass media and health care professionals and of own unfavourable coping with external and internal concerns.Issues related to negative stereotypes of psychiatry include overestimation of coercion, associative stigma, lack of public knowledge, need of simplification of complex mental issues, problem of the continuum between normality and psychopathology, competition with medical and non-medical disciplines, and psychopharmacological treatment.Issues related to psychiatry's own contribution to being underestimated include lack of a clear professional identity, lack of biomarkers supporting clinical diagnoses, limited consensus about best treatment options, lack of collaboration with other medical disciplines and low recruitment rates among medical students.Much can be improved to achieve a positive self-concept, however, psychiatry will remain a profession with an exceptional position among the medical disciplines which should be seen as its specific strength.Disclosure of interestThe author has not supplied his declaration of competing interest.

Les personnes souffrant de maladies mentales severes telles que la schizophrenie, la depression ou le trouble bipolaire sont en moins bonne sante physique et ont une esperance de vie moindre que la population generale. La surmortalite cardiovasculaire associee a la schizophrenie et au trouble bipolaire est en partie attribuee a une majoration des facteurs de risque coronarien modifiables : obesite, tabagisme, diabete, hypertension et dyslipidemie. Les antipsychotiques et peut-etre d’autres psychotropes, les antidepresseurs par exemple, peuvent induire une prise de poids ou aggraver d’autres facteurs metaboliques de risque cardiovasculaire. Les patients peuvent avoir un acces restreint a la medecine generale, avec des opportunites de depistage et de prevention du risque cardiovasculaire inferieures a celles que l’on attendrait dans une population non psychiatrique. L’European Psychiatric Association (EPA), soutenue par l’European Association for the Study of Diabetes (EASD) et l’European Society of Cardiology (ESC), a publie cette declaration de position dans le but d’ameliorer la prise en charge des patients souffrant de maladies mentales severes. L’intention est d’amorcer une cooperation et une prise en charge partagee entre les differents professionnels de la sante et de sensibiliser les psychiatres et les medecins de premiere ligne qui s’occupent de patients souffrant de maladies mentales severes au depistage et au traitement des facteurs de risque cardiovasculaire et du diabete.

Introduction Long duration of untreated psychosis (DUP) predicts poor short- and long-term outcome in schizophrenia. It may also be a marker of resilience and associate with lower doses or shorter periods of using antipsychotic medication which may or may not be correlated with the association between DUP and outcome. Objectives To study the association between DUP and the use of antipsychotic medication in long-term follow-up. Aims To find out whether the delayed treatment in first-episode psychosis associates with using less antipsychotic medication during the course of illness Methods In the prospective Northern Finland 1966 Birth Cohort length of DUP and information on lifetime use of antipsychotic medication for 60 individuals with schizophrenia was assessed from medical records from the first episode until age 34 years. Association between length of DUP and cumulative dose-years of antipsychotics was analysed using linear regression analysis. Logarithmic transformations of DUP and dose years were used. Results Mean DUP was 227 days (SD 359) and mean of cumulative dose years was 2.41 (SD 1.29). Symptoms measured using PANSS ranged from 30 to 122, mean 53 (SD 21). Duration of untreated psychosis did not associate with the use of antipsychotic medication (beta = −0.124, p = 0.343). Conclusions There was no evidence of an association between DUP and the use of antipsychotic medication. Although long DUP has long-term association with poor outcome, it does not have an association with the use of antipsychotic medication based on the population-based long-term follow-up.

Off label use of psychopharmacy is in widespread use. Some psychiatric disorders are more treated off label – this was for long time the case for bipolar disorder and probably still is – than in label. What is off label medication? All medications without a proper licence by the respective drug authority? That means also medications which have a licence in another country/region off label, if not licenced in the respective country? That includes also medications which demonstrated evidence based efficacy and which are suggested in guidelines, but (so far) no licenced? The term regulates in a very strict way the use of certain compounds, while refusing others which are believed to belong to the state of art or even to be innovative. The pros and cons of off label medication are described using the off label use of antidepressants as example. The antidepressants – in the beginning the tricyclics and later on novel antidepressants with anti-histminergic profile – started to be widely used off label, after the ban of the benzodiazepines, for the treatment of nervousness, anxiety, sleep problems (for long-time especially amitryptiline, doxepine, mianserine, mirtazapine, trimipamine). With the upcoming interest in bipolar depression the discussion started, whether the use of antidepressants is off label in this indication or supported by the general indication major depression. The use of antidepressant in personality disorders is off label, but has a long clinical tradition, although the cost – benefit – relation is unclear (induction of outbursts, induction of suicidality). The use of some special antidepressant (tricyclics especially amitryptiline, novel dual antidepressants) as adjunctive to pain therapy is partially in label, partially off label.

There is a widely accepted traditional understanding among experts, that the therapeutic benefits of neuroleptic short and long-term treatment of people suffering from schizophrenic psychosis are so relevant for the life of these people as well as also from the viewpoint of the society that in comparison the typical side effects of the antipsychotic medication can be neglected. This position is expressed in all national and international guidelines, like for example the WFSBP guidelines. The efficacy of antipsychotics in reducing the symptoms of the acute episode as well as in relapse prevention are well documented in the sense of EBM and most of the side effects are only transient or can be reduced by adequate measures. However this position probably has to be re-discussed given the fact that data coming from few naturalistic studies raised the question, whether long-term treatment with antipsychotics can lead to brain alterations which in consequence might be negative for brain functioning. This is a serious issue which needs further research in control group studies, because naturalistic studies are often biased in their results. Altogether the respective results are not consistent. One RCT and one naturalistic follow up study suggest that atypical antipsychotic like clozapine or olanzapine are not associated with brain volume changes. Also this needs further investigation as well as discussions concerning potential consequences for the current treatment procedures. Apparently in the treatment guidelines this differentiation so far was neglected.

There was a missing affiliation for Prof. Dr. med. Hans-Jurgen Moller in this article: Department of Psychiatry, Ludwig-Maximilians-University Munich, Munich, Germany. The articles which are cited as ‘‘in press’’ ([2], [3], [5], [7], [10], and [12]) are from the same special issue, European Psychiatry 27 (2012) and should be cited as below: [2] Campion J, Bhui K, Bhugra D. EPA guidance on prevention of mental illness. Eur Psy 27 (2012) 68–80. [3] Gaebel W, Becker T, Janssen B, Munk-Jorgensen P, Musalek M, Rossler W, et al. EPA guidance on quality of mental health services. Eur Psy 27 (2012) 87–113.

Introduction The ongoing debate whether to look at psychiatric disorders from a categorical or a dimensional perspective provokes objections, whatever viewpoint is taken. On the one hand, a dimensional approach seems to be superior in terms of predictive validity. On the other hand, the currently applied categorical approach, its usefulness and simplicity should not be neglected. Aim/objectives To demonstrate a possibility to combine the categorical and the dimensional perspective at the same time. Methods We introduce a diagnostic map that was calculated by robust nonmetric multidimensional scaling based on AMDP symptom profiles of N = 100 patients with schizophrenic and affective disorders. Results In the diagnostic map, a manic, a depressive, and a non-affective cluster clearly emerged. At the same time, the mania dimension (r = 0.82), the depression dimension (r = 0.68), and the apathy dimension (r = 0.74) showed high multiple regression values in the map (Figure 1). Conclusions We found the association and quality of mood symptoms to be a structuring principle in a diagnostic map. We demonstrated that this approach represents a promising way of combining the categorical and the dimensional perspective. As a practical implementation of these findings, a multidimensional diagnostic map could serve as an automated diagnostic tool based on psychopathological symptom profiles. Download : Download full-size image [Figure 1]

It is not much more than a hundred years ago that psychiatry started to become a scientific discipline in the sense of a modern medical science. This statement is especially true if we focus on psychiatry as a discipline of neurobiology/neuroscience. The key inventions in psychopharmacology were reached not earlier than the 50ies of the last century. The detection of antipsychotic, antidepressive, tranquilising and mood stabilising medication at that time can be regarded as a therapeutic revolution in psychiatry, given the fact that from today's point of view no meaningful biologically oriented treatment procedures were available apart from ECT. In this pioneer time of psychopharmacology, psychopharmacological treatment became one of the main treatment approaches. This was in principal a success story, however also several limitations such as unsatisfying efficacy, tolerability problems etc. were to be observed in the following decades. In the last 20 to 30 years second generation of antipsychotics and antidepressants entered the market, developed to overcome some of these problems. There are still unmet needs in treating mental disorders with polypharmacy which can hopefully be reduced significantly in the near future. These unmet needs are related among others to delay of onset of therapeutic action, unsatisfying effect size, problems in treating medication refractory patients, side effect which are subjectively or objectively disturbing, some of them leading to problems e.g. in terms of metabolic issues. Although there has always been the theoretically based postulate that patients should be treated with monotherapy, clinicians tried to overcome at least some of these problems by switching strategies, comedication and augmentation strategies, believed to be meaningful due to clinical experience, although still lacking in evidence.

There is growing evidence of abnormalities of high-frequency oscillations in the gamma range of the electroencephalography in schizophrenia. The generation of neural activity in the gammaband was shown to be critically related to a glutamatergic and GABAergic microcircuit which is also known to be involved in the pathophysiology of schizophrenia. One example of such gamma oscillations is the early auditory evoked gamma band response (aeGBR). We aimed to investigate whether there are altered aeGBR and activity of its sources in the anterior cingulate cortex and/or the auditory cortex (identified as sources of the GBR previously) in schizophrenic patients and in first-degree relatives of schizophrenia patients. We investigated the early aeGBR and its sources (LORETA source localisation) in 90 medicated patients with schizophrenia and in 17 unaffected first-degree relatives of patients with schizophrenia using an auditory reaction task (comparison with age-, gender- and educational-level-matched control groups). Evoked power and phase locking of the aeGBR was reduced in schizophrenia patients and healthy first-degree relatives of patients with schizophrenia. This effect was due to a reduced activity in the auditory cortex and the anterior cingulate cortex. The findings are in line with the hypothesis of a disturbed GABAergic interneural modulation of pyramidal cells in schizophrenia and findings of different schizophrenia risk genes associated with transmission at glutamatergic and GABAergic synapses. The results regarding the first-degree relatives of patients with schizophrenia point to the applicability of this marker as a heritable intermediate phenotype for schizophrenia.

BackgroundTDCS for modulating neurophysiology is known since the 1960s. tDCS trials in patients with depression showed promising results.Methods22 patients with therapy resistant major depression (DSM-IV criteria) were included in a four week cross-over trial, 10 received 1 mA tDCS, 12 received 2 mA tDCS, 2 dropped out. Patients received add-on tDCS under a stable antidepressant treatment over 3 weeks and were randomized to active or sham tDCS treatment. The sham condition was evaluated in 10 healthy volunteers and was indistinguishable.Both, active (1 mA resp. 2 mA) and placebo tDCS were applied for 20 min per day and for two weeks and then switched to the other condition. The anode was positioned over F3 and the cathode over the contralateral supraorbital region. For placebo tDCS a novel sham device (neuroConn, llmenau, Germany) was used which is indistinguishable for the applying person. Severity of depression was assessed by HAMD, BDI, CGI and CORE scales and raters were blind to treatment conditions.ResultsMean HAMD decreased by 25% in the whole population after four weeks of tDCS. Active tDCS performed significantly better (p = 0.0492) than the control treatment. However this positive association was restricted to the first study phase as there was also a significant (p = 0.0271) influence of the study phase in the cross-over design and an almost significant (p = 0.0864) interaction between treatment and study phase.ConclusionThough active tDCS was not superior to sham treatment, we observed hangover effects in weeks 3 and 4 depending on the first condition.

A number of studies has been performed recently on the efficacy and tolerability of silexan, a novel preparation from lavender oil for oral use, in the treatment of anxiety disorders and related conditions with particular attention to subthreshold generalized anxiety disorder (GAD). Three randomized, double-blind clinical trials were identified which investigated the efficacy of silexan in subsynromal anxiety disorder (vs. placebo; 10 weeks’ treatment), in GAD (vs. lorazepam; 6 weeks), and in restlessness and agitation (vs. placebo; 10 weeks) according to DSM-IV and ICD-10 criteria. One open-label pilot study assessed the potential of the medicinal product in neurasthenia, posttraumatic stress disorder and somatization disorder (6 weeks). All trials assessed the participants’ anxiety levels using the Hamilton Anxiety Scale (HAMA) or the State Trait Anxiety Inventory (STAI) as well as measures of co-morbidity and clinical global impressions. Across all trials 280 patients were exposed to silexan 80 mg/day, 37 were treated with lorazepam 0.5 mg/day and 192 received placebo. Average within group HAMA total scores at baseline ranged between 24.7 and 27.1 points. Patients treated with silexan showed average HAMA total score decreases by between 10.4 ± 7.1 and 12.0 ± 7.2 points at week 6 and by between 11.8 ± 7.7 and 16.0 ± 8.3 points at week 10. In subthreshold GAD silexan was significantly superior to placebo, with a mean value difference of at least 4 points (lower bound of 95% confidence interval (CI)) after 10 weeks. In GAD silexan and lorazepam showed comparable HAMA total score reductions (90% CI for mean value difference: -2.3; 2.8 points). The decrease of anxiety levels was accompanied by a reduction of restlessness and co-morbidity, and by improvements in general well-being. The anxiolytic effect of silexan is superior to placebo and comparable to lorazepam in subthreshold and threshold GAD, respectively. The medicinal product also improved associated symptoms like restlessness, disturbed sleep and somatic complaints, and had a beneficial influence on general well-being and quality of life. Silexan may offer interesting perspectives particularly in the treatment of subthreshold GAD.

ObjectivesDriving is a daily activity for most people in developed countries and is important in maintaining independence. Bipolar patients may have an impaired driving behavior because of the pathology itself, with psychomotor and cognitive disturbances. Additionally, adverse effects of pharmacologic treatment may be detrimental.Methods24 remitted bipolar outpatients diagnosed according to ICD-10 criteria were enrolled in the study, receiving either lithium (n = 12) or lamotrigine (n = 12). Participants were investigated under steady state plasma level conditions. According to the German Guidelines for road and traffic safety data were collected with the Wiener Testsystem (WTS) measuring visual perception, reactivity, stress tolerance, concentration and vigilance.Psychopathologic symptoms were rated with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Young Mania Rating Scale - Clinician rated (YMRS-C).ResultsAbout 40% of patients were without clinically relevant psychomotor disturbances. In 40% of cases mild to moderate impairments could be seen, and 20% of the patients were considered as severely impaired. Data show that patients under lamotrigine had an altogether better test performance than patients treated with lithium. Especially in visual perception and stress tolerance differences were most pronounced.ConclusionsAbout 20% of remitted bipolar outpatients treated with lithium or lamotrigine must be considered unfit to drive. In 40% of the cases it seems justified to counsel patients individually, taking into account compensational factors. Analysis of our data point to an advantage for bipolar patients treated with lamotrigine when compared with lithium. However causal relationships can not be drawn from our data.

The efficacy of antidepressants is clinically relevant. The highest effect size was demonstrated for severe depression. Based on responder rates and based on double-blind placebo-controlled studies, the number needed to treat (NNT) is 5–7 for acute treatment and 4 for maintenance treatment. Monotherapy with one drug is often not sufficient but has to be followed by other antidepressants or by comedication/augmentation therapy approaches.Generally, antidepressants reduce suicidality, but under special conditions like young age or personality disorder, they can also increase suicidality. However, under the conditions of good clinical practice, the risk-benefit relationship of treatment with antidepressants can be judged as favourable also in this respect.The capacity of psychiatrists to individualise and optimise treatment decisions in terms ofthe right drug/treatment for the right patient’ is still restricted since currently there are no sufficient powerful clinical or biological predictors which could help to achieve this goal. There is hope that in future pharmacogenetics will contribute significantly to a personalised treatment. With regard to plasma concentration, therapeutic drug monitoring (TDM) is a useful tool to optimize plasma levels therapeutic outcome.

This position statement will address in an evidence-based approach some of the important issues and controversies of current drug treatment of depression such as the efficacy of antidepressants, their effect on suicidality, their place in a complex psychiatric treatment strategy including psychotherapy.The efficacy of antidepressants is clinically relevant. The highest effect size was demonstrated for severe depression. Based on responder rates and based on double-blind placebo-controlled studies, the number needed to treat (NNT) is 5–7 for acute treatment and 4 for maintenance treatment. Monotherapy with one drug is often not sufficient but has to be followed by other antidepressants or by comedication/augmentation therapy approaches.Generally antidepressants reduce suicidality, but under special conditions like young age or personality disorder, they can also increase suicidality. However, under the conditions of good clinical practice, the risk-benefit relationship of treatment with antidepressants can be judged as favourable also in this respect.The capacity of psychiatrists to individualise and optimise treatment decisions in terms of ‘the right drug/treatment for the right patient’ is still restricted since currently there are no sufficient powerful clinical or biological predictors which could help to achieve this goal. There is hope that in future pharmacogenetics will contribute significantly to a personalised treatment. With regard to plasma concentration, therapeutic drug monitoring (TDM) is a useful tool to optimize plasma levels therapeutic outcome.The ideal that all steps of clinical decision making can be based on evidence-based medicine is far away from reality. Clinical experience still has a great impact.

ObjectiveTo investigate the association of early improvement and treatment emergent suicidal ideation in a large sample (N=705) of naturalistically treated inpatients with major depressive disorderMethodIn line with previous reports early improvement was defined as a 20% HAMD improvement within the first two weeks of antidepressant treatment. Treatment emergent suicidal ideation was defined by a sudden increase from 0 or 1 to at least 3 on HAM-D item-3 and from 0,1 to at least 4 on MADR item 10 for suicidal ideation. Early improvers were compared with non-early improvers with respect to the occurrence of treatment emergent suicidality during treatment.ResultsEarly improvers were 3 (MADRS) to 3.4 (HAMD) times less likely to experience new emergence of suicidal ideation during the treatment course than non-improvers. In addition, early improvement was associated with significantly less pessimistic thoughts.LimitationsThe analysis is based on secondary analysis of prospectively collected data. No controlled study design.ConclusionEarly improvement is associated with significantly less treatment emergent suicidal ideation for it my may provide rapid symptom relief and reduce hopelessness.

Pharmacogenetics in schizophrenia comprises pharmacokinetical and pharmacodynamical aspects as well as an approach to identify candidate genes associated with therapy response or side effects. Firstly focussing on classical drug targets like dopaminergic or serotonergic receptors, currently also developmental and regulatory genes presumably associated with effects of antipsychotic therapy are identified. The aim of this study was to investigate associations between therapy response in schizophrenic patients and different polymorphisms previously been identified within a genome wide array in rodents treated with MK-801 and/or haloperidol combined with some well-known schizophrenia candidate genes. We genotyped for 200 different polymorphisms in 285 schizophrenic patients, who were treated with different antipsychotics within randomized controlled trials. Psychopathology was measured weekly using the PANSS scale. Correlations between psychopathology and genotypes were calculated by using a linear model (ANCOVA).We found significant associations between some well-known candidate genes (e.g. D2-, 5HT1A-, and α1A-receptors) and different PANSS subscales at baseline and after four weeks of antipsychotic treatment considered as therapy response. Furthermore we also identified several significant associations between some genes introduced from the animal model and psychopathology at baseline and towards therapy response. Some of them were formerly described in the literature (e.g. Homer1, Phospholipase C and Transthyretin), but most of them have not been related to schizophrenia or antipsychotic treatment by now (e.g. PLEKHA6, CLIC6 and SOSTDC1).This indicates an involvement of genes in the pathophysiology of schizophrenia apart from yet known candidate genes and might further help in detecting differential therapy response in individuals with schizophrenia.

ObjectivesAtypical features are common among depressed primary care patients, but clinical trials testing the efficacy of psychopharmacological and/or psychotherapeutic treatment are lacking. This paper examines the efficacy of sertraline and cognitive behavioural therapy (CBT) among depressed patients with atypical features.MethodsAnalyses involve a double-blind comparison of sertraline versus placebo (N=47) and a single-blind comparison between CBT versus a guided self-help group (GSG) (N=48), with primary efficacy endpoints being the Inventory of Depressive Symptomatology (IDSC) and Hamilton Depression Scale (HAMD-17).ResultsIn intent-to-treat (ITT) analyses, the decrease on the IDSC scale (and HAMD-17) was greater after CBT compared to GSG: p=0.01 (HAMD-17: p=0.01). The difference between SSRI versus placebo was not significant: p=0.22 (HAMD-17: p=0.36). At endpoint, the CBT versus GSG difference in mean change from baseline IDSc scores was 7.69 points (HAMD-17: 4.97 points), the sertraline versus placebo difference was 3.07 points (HAMD-17: 0.59 points).ConclusionsThe data provide a preliminary suggestion that the mix of patients with minor or mild major depression with atypical features may not be best treated with an SSRI, but that these conditions might be amenable to CBT. Although SSRI were not superior to placebo, it would be premature to rule out SSRI as efficacious in atypical depression.

IntroductionThe effectiveness of electroconvulsive therapy (ECT) in pharmacotherapy resistant major depression and schizophrenia has been shown for all age groups. Nevertheless, age specific side effects such as greater cognitive impairment and higher somatic risks due to medical comorbidities and concomitant medication may be limiting factors in geriatric patients.MethodsWe retrospectively evaluated 4457 treatments in 380 patients. Clinical variables, treatment modalities, ictal and postictal neurophysiological parameters were analysed. For modelling the influence of age on these varibles of interest, linear regression models, if necessary logistic regression models, were performed (statistical software package R 2.8.1).ResultsWe found a considerable clinical improvement over all age groups. Higher severity of disease at admission came up with a better clinical response. In comparison of the whole patient sample versus the elderly over the age of 60, there were no significant differences in need and number of concomitant psychotropic, but in medical co-medication. Ictal and postictal EEG parameters were only in part predictive for clinical outcome, but age had a significant influence on most of them. Cardiovascular side effects and cognitive disturbances were more frequent in the elderly but were only transient, and in most cases there was no need for any specific treatment.ConclusionsThe outcome results show excellent effectiveness and tolerability of ECT in all age groups. The very old are more prone to adverse events, but nonetheless tolerate ECT well and are likely to benefit.

IntroductionSince the introduction of second generation antipsychotics (SGA) extrapyramidal-motor symptoms (EPS) have become a lesser problem in the treatment of schizophrenic patients. Yet, some SGAs display these adverse events and first generation antipsychotics are still widely used. Several genetic polymorphisms have been found to be associated with the occurance of EPS.ObjectivesIn this study we tried to identify genes related to EPS from an animal model and then replicated the findings in schizophrenic patients.AimsTo identify new genes and show their relevance in the treatment of schizophrenic patients.MethodsRats were treated with haloperidol or saline and differential gene expression was assessed by using microarrays. We genotyped 285 schizophrenic patients for candidate genes and differentially expressed genes derived from the animal model. All patients were treated monotherapeutically with different antipsychotics within randomized controlled trials. EPS were assessed weekly using the ESRS and BAS. We used a linear model (ANCOVA) with PANSS total at baseline, type of medication and premedication as covariates for all investigated SNP's.ResultsWe found several SNPs to be associated with the occurance of EPS. The best results were obtained for SNPs within the genes of Phospholipase C epsilon 1 (PLCe1), Methionine Sulfoxide Reductase B3 (MSRB3), Chloride Intracellular Channel 6 (CLIC6), Prolactin Receptor (PRLR) and Dopamine Receptor D4 (DRD4). Effect sizes were between 1.7 and 4.9.ConclusionsWe could replicate some findings of the literature and identified four new genes possibly related to EPS. Some of these genes were recently related to schizophrenia.

Although there is no doubt about its efficiency, pharmacotherapy of depression still faces several problems that have to be focused upon and hopefully solved. Besides the problem of drug-resistance and delayed response, the need to achieve remission has become increasingly important.As for the near future, there is great hope that new mechanisms of action can overcome the limitations of the traditional and current antidepressant medications. Unfortunately, some of the recent developments that raised the most interest either turned out to be less effective than hoped, such as the substance P antagonists, or did not yet lead to a drug likely to be marketed in the near future, such as CRF antagonists, for example. On the other hand the first melatonergic antidepressant, agomelatine, is seen as a successful new development.Drug development can currently be based on improved brain imaging techniques, better animal models, and an increased knowledge of genetic markers. Hopefully this will result in a change in the pharmacotherapy of depression and psychiatric diseases in general. From a clinical point of view, new antidepressants should target the following unmet needs: early onset of action; increased proportion of remission; broad spectrum of efficacy including physical symptoms, pain, sleep disorders, circadian rhythm disorders, etc; good efficacy in subtypes of depression, such as atypical depression; efficacy in bipolar depression without inducing switches to mania; lack of side effects of TCAs and modern antidepressants, especially lack of cardiac side effects, anticholinergic side effects, sedation, weight gain, sexual side effects, etc.

The aim of this paper was to evaluate the efficacy of risperidone long-acting injectable (RLAI) for reducing negative symptoms of schizophrenia in patients with predominantly negative symptoms at baseline. A subanalysis was performed on data from the 6-month, open-label Switch to Risperidone Microspheres trial. Patients with Positive and Negative Syndrome Scale (PANSS) negative subscale score ≥21, which was higher than their PANSS positive subscale score, were included in this subanalysis. Improvement in negative symptoms was measured by assessing change in the PANSS negative subscale and a negative factor score. Additional outcome variables included measures in general functioning, quality of life and patient satisfaction. A total of 842 patients were eligible for inclusion in this subanalysis. Six months of treatment was completed by 631 (74.9%) patients. Forty-three (5.1%) patients discontinued treatment due to an adverse event. Negative symptoms were significantly reduced by 6.1 ± 6.3 points for the PANSS negative score and 6.1 ± 6.4 points for the negative factor score ( P < 0.0001 for both). Significant improvements were also noted for total PANSS and other PANSS subscale scores, general functioning, quality of life and patient satisfaction ( P < 0.0001). The most common treatment-emergent adverse events (>5%) were: anxiety (6.8% of patients), exacerbation of disease (6.2%) and insomnia (5.7%). Overall, RLAI was well tolerated and associated with significant reductions in movement disorder severity. The treatment resulted in a significant improvement in negative symptom severity and was well tolerated in patients with predominantly negative symptoms, who switched from a stable antipsychotic regimen.