Quality indicators for mental healthcare in the Danube region: results from a pilot feasibility study.

Quality indicators are vital for monitoring the transformation of institution-based mental health services towards the provision of person-centered mental healthcare. While several mental healthcare quality indicators have been identified as relevant and valid, their actual usability and utility for routine monitoring healthcare quality over time is significantly determined by the availability and trustworthiness of the underlying data. In this feasibility study, quality indicators that have been systematically identified for use in the Danube region countries of Bulgaria, the Czech Republic, Hungary, and Serbia were measured on the basis of existing mental healthcare data in the four countries. Data were collected retrospectively by means of the best available, most standardized, trustworthy, and up-to-date data in each country. Out of 21 proposed quality indicators, 18 could be measured in Hungary, 17 could be measured in Bulgaria and in the Czech Republic, and 8 could be measured in Serbia. The results demonstrate that a majority of quality indicators can be measured in most of the countries by means of already existing data, thereby demonstrating the feasibility of quality measurement and regular quality monitoring. However, data availability and usability are scattered across countries and care sectors, which leads to variations in the quality of the quality indicators themselves. Making the planning and outputs of national mental healthcare reforms more transparent and evidence-based requires (trans-)national standardization of healthcare quality data, their routine availability and standardized assessment, and the regular reporting of quality indicators.

Psychiatrist's adherence: a new factor in relapse prevention of schizophrenia. A randomized controlled study on relapse control through telemedicine system.

ACCESSIBLE SUMMARY: Exposure to psychotic states has detrimental effects on the long-term outcome of schizophrenia and brain integrity. Therefore, improving relapse prevention is a key component of long-term management of schizophrenia. Previous studies using continuous monitoring of an individual's early signs of relapse and adopting preventative pharmacological interventions, when early signs are detected, showed promising clinical results in terms of relapse risk reduction. This 18-month multi-centre parallel randomized controlled, open label, trial with telemedicine relapse prevention programme ITAREPS failed to show superiority of maintenance plus prodrome-based targeted medication strategy over treatment as usual. The study, marked by low investigator's adherence, confirmed that absence of pharmacological intervention at early stage of prodrome, critically influenced the risk of relapse. This and previous randomized controlled trials with telemedicine programme ITAREPS suggested that substantial improvement in relapse prevention in schizophrenia is likely to be unattainable under current clinical settings. Future preventive strategies in schizophrenia would require rapid pharmacological intervention upon occurrence of subclinical prodromal symptoms that are undetectable under conventional outpatient practice. Studies with ITAREPS suggested that integration of telemedicine relapse prevention systems and visiting nurse service might together represent practical solution capable to address those requirements. ABSTRACT: The Information Technology Aided Relapse Prevention Programme in Schizophrenia (ITAREPS) presents a telemedicine solution for weekly monitoring and management of schizophrenia. This study aims to evaluate the effectiveness of the programme in reducing the number of hospitalizations during the 18-month multi-centre parallel randomized controlled, open label, trial. Outpatients with schizophrenia or schizoaffective disorder were randomized to the active (n = 74) or control group (n = 72). In the active arm, investigators increased the antipsychotic dose upon occurrence of prodrome announced by the system. Intention-to-treat analysis showed no between-group difference in the hospitalization-free survival rate [Kaplan-Meier method; hazard ratio (HR) = 1.21, 95% confidence interval (CI): 0.56-2.61, P = 0.6). In a post hoc multivariate Cox proportional hazards model, out of 13 potential predictors, only ITAREPS-related variables (number of alerts without pharmacological intervention/HR = 1.38, P = 0.042/ and patient non-adherence with ITAREPS /HR = 1.08, P = 0.009/) increased the risk of hospitalization. In this trial ITAREPS was not effective. The results in context with previous ITAREPS studies suggest non-adherence of both psychiatrists and patients as the main reasons for the failure of this preventive strategy. Tertiary prevention in schizophrenia have to be regarded a major challenge, warranting the need for implementation of strategies with more active participation of both patient and treating psychiatrist.

EPA guidance on the role and responsibilities of psychiatrists.

Psychiatry is that branch of the medical profession, which deals with the origin, diagnosis, prevention, and management of mental disorders or mental illness, emotional and behavioural disturbances. Thus, a psychiatrist is a trained doctor who has received further training in the field of diagnosing and managing mental illnesses, mental disorders and emotional and behavioural disturbances. This EPA Guidance document was developed following consultation and literature searches as well as grey literature and was approved by the EPA Guidance Committee. The role and responsibilities of the psychiatrist include planning and delivering high quality services within the resources available and to advocate for the patients and the services. The European Psychiatric Association seeks to rise to the challenge of articulating these roles and responsibilities. This EPA Guidance is directed towards psychiatrists and the medical profession as a whole, towards other members of the multidisciplinary teams as well as to employers and other stakeholders such as policy makers and patients and their families.

White matter changes in first episode psychosis and their relation to the size of sample studied: a DTI study.

BACKGROUND: White matter abnormality has been recently proposed as a pathophysiological feature of schizophrenia (SZ). However, most of the data available has been gathered from chronic patients, and was therefore possibly confounded by factors such as duration of the disease, and treatment received. The extent and localization of these changes is also not clear. METHODS: We examined a population of early stage SZ patients using diffusion tensor imaging (DTI). 77 SZ patients and 60 healthy controls (HCs) were included in the analysis using Tract-Based Spatial Statistics (TBSS). We have also analyzed 250 randomly created subsets of the original cohort, to investigate the relation between the result of TBSS analysis, and the size of the sample studied. RESULTS: We have found a significant decrease in fractional anisotropy (FA) in the patient group. This change is present in most major white matter (WM) tracts including the corpus callosum, superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculus, and posterior thalamic radiation. Furthermore, we identified a clear trend towards an increase in the number and spatial extent of significant voxels reported, with an increasing number of subjects included in the analysis. CONCLUSION: Our study shows that FA is significantly decreased in patients at an early stage of schizophrenia, and that the extent of this finding is dependent on the size of studied sample; therefore underpowered studies might produce results with false spatial localization.

Differences in onset of disease and severity of psychopathology between toxoplasmosis-related and toxoplasmosis-unrelated schizophrenia.

OBJECTIVE: Toxoplasmosis is a lifelong parasitic disease that appears to be associated to schizophrenia. However, no distinguishing attributes in Toxoplasma-infected schizophrenia patients have been described as yet. METHOD: We searched for differences in symptom profile, cognitive performance and treatment response between 194 Toxoplasma-free and 57 (22.7%) Toxoplasma-infected schizophrenia patients treated in Prague Psychiatric Centre between 2000 and 2010. RESULTS: Infected and non-infected patients differed in severity of symptoms (P = 0.032) measured with the Positive and Negative Symptom Scale (PANSS). Infected patients scored higher in positive subscale of PANSS, but not in the general and negative subscales. Infected men scored higher also in Total PANSS score, and negative, reality distortion, disorganisation and cognitive scores. Higher PANSS scores of positive, negative and disorganised psychopathology were associated with the lower titres of anti-Toxoplasma antibodies suggesting that psychopathology deteriorates with duration of parasitic infection. Infected patients remained about 33 days longer in hospital during their last admission than uninfected ones (P = 0.003). Schizophrenia started approximately 1 year earlier in infected men and about 3 years later in infected women, no such difference was observed in uninfected subjects. CONCLUSION: Latent toxoplasmosis in schizophrenia may lead to more severe positive psychopathology and perhaps less favourable course of schizophrenia.

The early improvement of depressive symptoms as a potential predictor of response to antidepressants in depressive patients who failed to respond to previous antidepressant treatments. Analysis of naturalistic data.

INTRODUCTION: Current studies suggest that improvement of depressive symptoms after 2 weeks of treatment could predict the subsequent response. The aim of our study was to compare the predictive effect of early improvement (EI) after 1 and 2 weeks of treatment in patients who had failed to respond to previous antidepressant treatments (≥1 unsuccessful antidepressant trial). METHOD: Seventy-one subjects were treated (≥4 weeks) with various antidepressants chosen according to the judgment of attending psychiatrists. We used three definitions of EI (MADRS reduction ≥20, 25, 30%) at both time points. Areas under curve (AUC) were calculated to compare predictive effect of EI. RESULTS: We found lower MADRS scores in weeks 1 and 2 in responders (≥50% reduction of MADRS, n=35) compared to nonresponders. AUCs of MADRS reduction for response prediction at week 1 and 2 were not significantly different (0.73 vs 0.8; p=0.24). CONCLUSION: The results indicate that improvement of depressive symptoms in the treatment of resistant patients may occur after the first week of treatment. The predictive potential might be comparable to that found after the second week of antidepressant intervention and be clinically meaningful.

European Psychiatric Association guidance on the conflicts of interest.

Conflict of interest (COI) is a set of circumstances that creates a risk that professional judgments or actions regarding a primary interest will be unduly influenced and compromised by a secondary interest. It might arise in clinical practice, research, and education, and might include individuals and institutions. Primary interests include the pursuit of well-being of patients, ensuring the independence of medical education, and protecting the objectivity and integrity of medical research. Secondary interests might involve financial interests, pursuit of recognition and professional career advancement. COI might result from the multiple roles of physicians in patient care, research, administration, provision of expert opinion and policy advice, and consultancy to commercial organizations. The purpose of the COI policy is to protect the interests of the patients, strengthen the integrity of the profession, and preserve public trust in medicine and psychiatry. The aim of the guidance is to eventually prevent these conflicts from arising rather than remediate them ex post. It is desirable to identify factors that might lead to their occurrence, offer a framework for their recognition and assessment, introduce the principles and standards of their disclosure, and provide recommendations for their transparent resolution.

Position statement of the European Psychiatric Association (EPA) on the value of antidepressants in the treatment of unipolar depression.

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.

Subanesthetic dose of ketamine decreases prefrontal theta cordance in healthy volunteers: implications for antidepressant effect.

BACKGROUND: Theta cordance is a novel quantitative electroencephalography (QEEG) measure that correlates with cerebral perfusion. A series of clinical studies has demonstrated that the prefrontal theta cordance value decreases after 1 week of treatment in responders to antidepressants and that this effect precedes clinical improvement. Ketamine, a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, has a unique rapid antidepressant effect but its influence on theta cordance is unknown. METHOD: In a double-blind, cross-over, placebo-controlled experiment we studied the acute effect of ketamine (0.54 mg/kg within 30 min) on theta cordance in a group of 20 healthy volunteers. RESULTS: Ketamine infusion induced a decrease in prefrontal theta cordance and an increase in the central region theta cordance after 10 and 30 min. The change in prefrontal theta cordance correlated with ketamine and norketamine blood levels after 10 min of ketamine infusion. CONCLUSIONS: Our data indicate that ketamine infusion immediately induces changes similar to those that monoamineric-based antidepressants induce gradually. The reduction in theta cordance could be a marker and a predictor of the fast-acting antidepressant effect of ketamine, a hypothesis that could be tested in depressive patients treated with ketamine.

The Information Technology Aided Relapse Prevention Programme in Schizophrenia: an extension of a mirror-design follow-up.

AIMS: Decreasing a number of hospital admissions is important for improving outcomes for people with schizophrenia. The Information Technology Aided Relapse Prevention Programme in Schizophrenia (ITAREPS) programme enables early pharmacological intervention in psychosis by identification of prodromal symptoms of relapse using home telemonitoring via a phone-to-PC SMS platform. METHODS: This study was a 1-year extension of a previously published mirror-design follow-up evaluation of programme clinical effectiveness. In total, 73 patients with psychotic illness (45 patients from original sample and 28 newly added subjects) collaborating with 56 family members participated in the clinical evaluation. RESULTS: There was a statistically significant 77% decrease in the number of hospitalisations during the mean 396.8 +/- 249.4 days of participation in ITAREPS, compared with the same time period before participation in ITAREPS (Wilcoxon-signed ranks test, p < 0.00001), as well as significantly reduced number of hospitalisation days when in the ITAREPS (2365 hospitalisation days before and 991 days after ITAREPS enrolment respectively, Wilcoxon-signed ranks test, p < 0.003). CONCLUSION: The ITAREPS programme represents an effective tool in the long-term treatment of patients with psychotic disorders.

Clinical and demographic characteristics of psychiatric patients seropositive for Borrelia burgdorferi.

PURPOSE: Borrelia burgdorferi (Bb) infection can affect the central nervous system and possibly lead to psychiatric disorders. We compared clinical and demographic variables in Bb seropositive and seronegative psychiatric patients and healthy controls. METHOD: Nine hundred and twenty-six consecutive psychiatric patients were screened for antibodies to Bb and compared with 884 simultaneously recruited healthy subjects. RESULTS: Contrary to healthy controls, seropositive psychiatric patients were significantly younger than seronegative ones. None of the studied psychiatric diagnostic categories exhibited stronger association with seropositivity. There were no differences between seropositive and seronegative psychiatric patients in hospitalization length, proportion of previously hospitalized patients and proportion of subjects with family history of psychiatric disorders. CONCLUSION: These findings elaborate on potential association between Bb infection and psychiatric morbidity, but fail to identify any specific clinical 'signature' of Bb infection.

The influence of low-frequency left prefrontal repetitive transcranial magnetic stimulation on memory for words but not for faces.

Brain imaging studies suggest localization of verbal working memory in the left dorsolateral prefrontal cortex (DLPFC) while face processing and memory is localized in the inferior temporal cortex and other brain areas. The goal of this study was to assess the effect of left DLPFC low-frequency repetitive transcranial magnetic stimulation (rTMS) on verbal recall and face recognition. The study revealed a significant decrease of free recall in word encoding under rTMS (110% of motor threshold, 0.9 Hz) in comparison with sham stimulation (p=0.03), while no significant difference was found with facial memory tests. Our findings support the essential role of the left DLPFC in word but not facial memory and confirm the content specific arrangement of cortical areas involved in semantic memory. As a non-invasive tool, rTMS is useful for cognitive brain mapping and the functional localization of the category specific memory system.

The effect of tryptophan depletion on brain activation measured by functional magnetic resonance imaging during the Stroop test in healthy subjects.

We investigated the role of serotonin in cognitive activation of the frontal cortex. The serotonergic system was affected by the administration of an amino acids mixture without tryptophan (tryptophan depletion). In a placebo-controlled double-blind cross-over study with 20 healthy volunteers, we tested the hypothesis that a tryptophan (serotonin) decrease affects the activation of prefrontal cortex by the Stroop test. Cognitive brain activation was evaluated by functional magnetic resonance imaging (fMRI). Tryptophan depletion decreased the plasma tryptophan level up to 90 % for five hours after the tryptophan-free drink had been consumed when compared with the same mixture with tryptophan (p?0.0001). Tryptophan depletion did not affect the Stroop test performance. We compared fMRI activation in both conditions (tryptophan depletion and placebo) with plasma tryptophan levels as the covariates. The tryptophan depletion increased the activation (fMRI signal) in the bilateral mediofrontal cortex, anterior cingulate and left dorsolateral prefrontal cortex. The present findings allow the postulate that serotonergic medial forebrain and cingulum bundle pathways play a role in the activity of cortical structures involved in Stroop test processing.

Alterations in calcium homeostasis as biological marker for mild Alzheimer's disease?

The calcium hypothesis of neurodegenerative disorders such as Alzheimer's disease (AD) suggests that altered cytosolic Ca(2+) levels ( Ca(2+) (i)) and/or disturbances in Ca2+ homeostasis concern cellular mechanisms underlying neuronal pathology. To search for a diagnostic marker of Alzheimer's disease, we measured cytosolic calcium concentrations in platelets of AD patients, age-matched control subjects (AMC), and vascular dementia (VD) patients. The ( Ca(2+) (i)) was determined using long wavelength indicator Fluo-3AM in 21 mild AD patients, 17 AMC, and 23 patients with VD. The basal values of [Ca(2+)](i) were significantly lower in AD compared to AMC. After the addition of 1 mM calcium, the [Ca(2+)](i) markedly increased in platelets of AD compared to AMC and VD. Measurement of calcium homeostasis could provide a very sensitive, but less specific biological marker of AD. These results support the hypothesis that influencing calcium homeostasis may provide a therapeutic strategy in dementia.

Hippocampal damage mediated by corticosteroids--a neuropsychiatric research challenge.

There is an increasing evidence that corticosteroids damage the hippocampus in rodents and in primates. Hippocampal atrophy induced by corticosteroids may play an important role in the pathogenesis of a range of neuropsychiatric disorders. Hippocampus is necessary for short-term memory consolidation and HPA axis regulation. Signs of hippocampal damage (HPA dysregulation in combination with memory impairment) are found in affective disorders, Alzheimer's disease and in posttraumatic stress disorder. MRI volumetry reveals reduced hippocampal volume in these diseases. Evidence supporting the "glucocorticoid hypothesis" of psychiatric disorders is reviewed in the first part of the paper. Unresolved questions concerning temporary aspects of neurodegeneration, causality, reversibility, type of damage, factors increasing hippocampal vulnerability, and both pharmacological (CRH antagonists, antiglucocorticoid drugs, GABA-ergic, serotonergic, glutamatergic agents) and non-pharmacological (psychotherapy) treatment approaches are discussed in the second part.

Cytosolic calcium alterations in platelets of patients with early stages of Alzheimer's disease.

Alterations in calcium homeostasis might be implicated in the neuropathology of Alzheimer's disease (AD). To date it is not clear whether changes in cytosolic calcium level ([Ca2+ ]i) are the result or the cause of pathogenic effects. In platelets of patients with early stages of AD, the basal values of [Ca2+]i in the absence of extracellular Ca2+ were significantly lower in comparison with age-matched and young controls. After the addition of 1 mM calcium into the incubation medium the [Ca2+]i markedly increased in platelets of AD patients whereas the increase only to a smaller extent was observed in control age-matched and young subjects. The present study proposes that calcium dysregulation during the whole disease period could not be uniform and according to our results the [Ca2+]i is reduced in the first stages of AD. We suggest that the disturbed calcium homeostasis in AD is an "early defect."

Rights and responsibilities of the psychiatric profession.

Psychiatry as a medical discipline relies on the authority of medicine that is associated with the help to a suffering and deserving individual. If this source of authority is obscured, the discipline will be blamed for serving as a social tool for controlling undesirable phenomena and practices. Psychiatry as a medical science accumulates knowledge on the relationship of biology and psychopathology. It can provide an explanation of the extent to which mental illness participates in socially undesirable behaviour and phenomena. But it cannot explain undesirable social phenomena as a mental illness of sorts, let alone offer an effective treatment for them. We should carefully guard the boundaries of psychiatry to prevent its abuse in the future.