István Bitter | Semmelweis University (original) (raw)

Papers by István Bitter

The Journal of Clinical Psychiatry, 2011

European Psychiatry, 2005

ObjectiveAntipsychotic medications may reduce hostile and aggressive behavior in schizophrenia. T... more ObjectiveAntipsychotic medications may reduce hostile and aggressive behavior in schizophrenia. This study compared the effectiveness of antipsychotics in the treatment of aggression.MethodThe Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study compares the effectiveness of antipsychotic treatments in practice setting. Schizophrenia outpatients who initiated or changed to a new antipsychotic are followed in this non-interventional, prospective observational study for up to 3 years, with 6-months data now available on the entire cohort (N = 7655). The presence or absence of verbal or physical hostility/aggression was assessed retrospectively for the period of 6 months before enrollment, and prospectively in the period of 6 months after enrollment (the study treatment period). At baseline, patients in five monotherapy treatment groups (combined N = 3135) were prescribed one of the treatments: clozapine, olanzapine, quetiapine, risperidone, or haloperidol, and had...

European Psychiatry, 2010

IntroductionOne type of the treatment interventions is the “off label” use of a drug, which may i... more IntroductionOne type of the treatment interventions is the “off label” use of a drug, which may include the use of a drug in a nonapproved indication, dose range, age group, drug combination and drug formulation. Research in this field is insufficient, while the medical, financial and legal consequences of off label use maybe serious. In case of off label use of a drug the manufacturer does not have any responsibility in case of adverse or serious adverse events.MethodsLabels (summary of product characteristics) of antipsychotic drugs have been compared for indications and examples of regulations for off label use have been collected.ResultsLabels (summary of product characteristics) very rarely include indications for children, adolescents and for the elderly. A significant proportion of psychotic disorders listed in DSM-IV or in ICD 10 and major clinical syndromes have not been included as indications in the label of antipsychotic drugs. The same compound marketed by different com...

Value in Health, 2006

date. This study provides an estimate of the cost-effectiveness of memantine compared with standa... more date. This study provides an estimate of the cost-effectiveness of memantine compared with standard care (no pharmacotherapy) in moderate to severe AD adapted to a Canadian setting and including all available evidence. No other pharmacological treatment was included in the evaluation as memantine is currently the only drug approved in this indication. METHODS: The progression of AD in terms of cognitive severity, functional disability and mortality was simulated over two-years using a state-transition (Markov) model. Outcomes of the model were Quality-Adjusted Life-Years (QALY) and costs from a societal perspective. The main cost and epidemiological input parameters of the model were computed using data from the Canadian Study on Health and Aging (CSHA). All relevant published and unpublished clinical trials of memantine versus placebo in moderate to severe AD were used to compute the transition probabilities between health states. A priori distributions were associated to all relevant parameters in order to enable stochastic analyses. RESULTS: Compared with standard care, the memantine strategy produced 0.03 additional QALYs, with no additional overall cost. Probabilistic sensitivity analyses give 83.3% chance that memantine treatment is cost neutral, 89.5% chance of being cost-effective if the decision-maker is willing to pay 20,000foraquality−adjustedlifeyearand96.220,000 for a quality-adjusted life year and 96.2% chance for a willingness-to-pay of 20,000foraquality−adjustedlifeyearand96.2100,000 per QALY. Robustness of the results was confirmed through one-way and scenario-based sensitivity analyses. CONCLUSIONS: Our evaluation found memantine dominant over standard care. Results were comparable with those published for acetylcholinesterase inhibitors indicated for treatment of earlier stages of AD.

Schizophrenia Research, 2013

Background: Emotional expressions are important acts of communication, and impairment in facial e... more Background: Emotional expressions are important acts of communication, and impairment in facial emotion recognition has been shown to be related to impairments in social cognition in schizophrenia. We used an event-related potential (ERP) paradigm to identify and delineate the temporal characteristics in the electrophysiological cascade related to fearful facial affect processing in patients with schizophrenia as compared to healthy controls. Methods: Twenty-four subjects with schizophrenia and 24 individually matched healthy controls participated in an emotion recognition task. Ekman faces displaying neutral and fearful facial expressions were used as stimuli. ERPs were recorded using a 128-channel EEG system. Results: Based on the analysis of Global Field Power (GFP) in the 150-190 ms time window both groups differentiated between fearful and neutral faces. Schizophrenia patients showed an additional differential processing of fearful vs. neutral faces in the 330-450 ms time window, and this ERP effect correlated with psychopathology. Conclusions: Both patients and healthy controls differentiate fearful and neutral faces in early phases of emotion processing. Our results also indicate that schizophrenia patients show increased responsivity to fearful faces at a later processing stage. This could be related to the overrating of negative emotions, and the symptomatology associated with fear processing in patients with schizophrenia.

Comprehensive Psychiatry, 2013

Background: While the number of symptoms of attention-deficit hyperactivity disorder (ADHD) decre... more Background: While the number of symptoms of attention-deficit hyperactivity disorder (ADHD) decreases with age, a high proportion of adults with ADHD symptoms suffer from persistent functional impairment (Fi) linked to these symptoms. Our objective was to investigate the specific roles of two potentially important predictors of this Fi: the clinical symptom presentation and the deficit in executive functions (EFs). Methods: A total of 158 subjects from a community sample positively screened for ADHD were classified into two groups: those with and without Fi. Following a detailed diagnostic process, participants were administered a self-rating scale for ADHD symptoms as well as a neuropsychological test battery containing tests of EF and attention relevant as potential cognitive endophenotypes for ADHD. Results: The overall number as well as the number of inattentive, hyperactive and impulsive symptoms, confirmed both by examiner and self-report, were significantly higher among Fi subjects. The highest odds ratio for Fi was associated with impulsive symptoms. Additionally, self-reported complaints of problems with self-concept were significantly higher among Fi subjects. No significant relationship between Fi and neuropsychological measures of EF and attention was detected. Conclusions: This study revealed that the number of symptoms, in particular that of impulsivity, had a significant impact on Fi in adults with symptoms of ADHD. Furthermore, our results underline the importance of assessing complaints and behaviors related to self-concept, which are not included in DSM-IV diagnostic criteria of ADHD but nonetheless may be associated with functional outcome of the disorder.

British Journal of Psychiatry, 2009

BackgroundIn spite of the growing literature about adult attention-deficit hyperactivity disorder... more BackgroundIn spite of the growing literature about adult attention-deficit hyperactivity disorder (ADHD), relatively little is known about the prevalence and correlates of this disorder.AimsTo estimate the prevalence of adult ADHD and to identify its demographic correlates using meta-regression analysis.MethodWe used the MEDLINE, PsycLit and EMBASE databases as well as hand-searching to find relevant publications.ResultsThe pooled prevalence of adult ADHD was 2.5% (95% CI 2.1–3.1). Gender and mean age, interacting with each other, were significantly related to prevalence of ADHD. Metaregression analysis indicated that the proportion of participants with ADHD decreased with age when men and women were equally represented in the sample.ConclusionsPrevalence of ADHD in adults declines with age in the general population. We think, however, that the unclear validity of DSM–IV diagnostic criteria for this condition can lead to reduced prevalence rates by underestimation of the prevalence ...

International Journal of Neuropsychopharmacology, 2017

Background: The atypical antipsychotic clozapine is effective in treatment-resistant schizophreni... more Background: The atypical antipsychotic clozapine is effective in treatment-resistant schizophrenia; however, the success or failure of clozapine therapy is substantially affected by the variables that impact the clozapine blood concentration. Thus, elucidating the inter-individual differences in clozapine pharmacokinetics can facilitate the personalized therapy. Methods: Since a potential role in clozapine metabolism is assigned to CYP1A2, CYP2C19, CYP2D6 and CYP3A enzymes, the association between the patients' CYP status (CYP genotypes, CYP expression) and clozapine clearance was evaluated in 92 psychiatric patients. Results: The patients' CYP2C19 or CYP2D6 genotypes and CYP1A2 expression seemed to have no effect on clozapine serum concentration, whereas CYP3A4 expression significantly influenced the normalized clozapine concentration (185.53 ± 56.53 in low expressers vs 78.05 ± 29.57 or 66.52 ± 0.25 (ng/mL)/(mg/kg) in normal or high expressers, P < .0001), in particular that the patients expressed CYP1A2 at a relatively low level. The functional CYP3A5*1 allele seemed to influence clozapine concentrations in those patients who expressed CYP3A4 at low levels. The dose requirement for the therapeutic concentration of clozapine was substantially lower in low CYP3A4 expresser patients than in normal/high expressers (2.18 ± 0.64 vs 4.98 ± 1.40 mg/kg, P < .0001). Furthermore, significantly higher plasma concentration ratios of norclozapine/ clozapine and clozapine N-oxide/clozapine were observed in the patients displaying normal/high CYP3A4 expression than in the low expressers. Conclusion: Prospective assaying of CYP3A-status (CYP3A4 expression, CYP3A5 genotype) may better identify the patients with higher risk of inefficiency or adverse reactions and may facilitate the improvement of personalized clozapine therapy; however, further clinical studies are required to prove the benefit of CYP3A testing for patients under clozapine therapy.

The lancet. Psychiatry, Jan 21, 2015

Mental and brain disorders represent the greatest health burden to Europe-not only for directly a... more Mental and brain disorders represent the greatest health burden to Europe-not only for directly affected individuals, but also for their caregivers and the wider society. They incur substantial economic costs through direct (and indirect) health-care and welfare spending, and via productivity losses, all of which substantially affect European development. Funding for research to mitigate these effects lags far behind the cost of mental and brain disorders to society. Here, we describe a comprehensive, coordinated mental health research agenda for Europe and worldwide. This agenda was based on systematic reviews of published work and consensus decision making by multidisciplinary scientific experts and affected stakeholders (more than 1000 in total): individuals with mental health problems and their families, health-care workers, policy makers, and funders. We generated six priorities that will, over the next 5-10 years, help to close the biggest gaps in mental health research in Eur...

International Journal of Methods in Psychiatric Research, 2013

Despite the high impact of mental disorders in society, European mental health research is at a c... more Despite the high impact of mental disorders in society, European mental health research is at a critical situation with a relatively low level of funding, and few advances been achieved during the last decade. The development of coordinated research policies and integrated research networks in mental health is lagging behind other disciplines in Europe, resulting in lower degree of cooperation and scientific impact. To reduce more efficiently the burden of mental disorders in Europe, a concerted new research agenda is necessary. The ROAMER (Roadmap for Mental Health Research in Europe) project, funded under the European Commission's Seventh Framework Programme, aims to develop a comprehensive and integrated mental health research agenda within the perspective of the European Union (EU) Horizon 2020 programme, with a translational goal, covering basic, clinical and public health research. ROAMER covers six major domains: infrastructures and capacity building, biomedicine, psychological research and treatments, social and economic issues, public health and well-being. Within each of them, state-of-the-art and strength, weakness and gap analyses were conducted before building consensus on future research priorities. The process is inclusive and participatory, incorporating a wide diversity of European expert researchers as well as the views of service users, carers, professionals and policy and funding institutions.

BMC Psychiatry, 2013

Background Treatment of patients with acute mania remains a considerable medical challenge since ... more Background Treatment of patients with acute mania remains a considerable medical challenge since onset of action of antimanic medication is delayed for several days. Psychostimulants could have an earlier onset of action. This assumption is based on the ‘vigilance regulation model of mania’ which postulates that vigilance is unstable in manic patients. Accordingly, vigilance-stabilising psychostimulants could be more useful than conventional treatment in acute mania. We present here the study protocol of a trial intended to study the efficacy and safety of methylphenidate in the initial treatment of acute mania. Methods/design A multi-centre, randomised, double-blind, placebo-controlled clinical trial will be conducted in 88 bipolar inpatients with acute mania. Male and female patients older than 18 years will be randomised to treatment with either methylphenidate (20 to 40 mg/day) or placebo for 2.5 days, given once or twice daily. The main outcome measure is the reduction in the Y...

Canadian journal of psychiatry. Revue canadienne de psychiatrie, 2003

To determine the antipsychotic efficacy and extrapyramidal safety of intramuscular (i.m.) olanzap... more To determine the antipsychotic efficacy and extrapyramidal safety of intramuscular (i.m.) olanzapine and i.m. haloperidol during the first 24 hours of treatment of acute schizophrenia. Patients (n = 311) with acute schizophrenia were randomly allocated (2:2:1) to receive i.m. olanzapine (10.0 mg, n = 131), i.m. haloperidol (7.5 mg, n = 126), or i.m. placebo (n = 54). After the first injection, i.m. olanzapine was comparable to i.m. haloperidol and superior to i.m. placebo for reducing mean change scores from baseline on the Brief Psychiatric Rating Scale (BRPS) Positive at 2 hours (-2.9 olanzapine, -2.7 haloperidol, and -1.5 placebo) and 24 hours (-2.8 olanzapine, -3.2 haloperidol, and -1.3 placebo); the BPRS Total at 2 hours (-14.2 olanzapine,-13.1 haloperidol, and -7.1 placebo) and 24 hours (-12.8 olanzapine, -12.9 haloperidol, and -6.2 placebo); and the Clinical Global Impressions (CGI) scale at 24 hours (-0.5 olanzapine, -0.5 haloperidol, and -0.1 placebo). Patients treated with...

Bulletin of the World Health Organization, 2000

Psychiatria Danubina, 2010

Deinstitutionalization has made possible the development of modern community psychiatric services... more Deinstitutionalization has made possible the development of modern community psychiatric services, however radical decrease in the number of hospital beds may result in a reduction in the overall standard of psychiatric care and disruptions in service delivery. The authors present an example of deinstitutionalisation in Hungary, which led to serious difficulties in the provision of healthcare in the field of psychiatry, contrasted with a case from Germany serving as an example of an alternative solution.

The World Journal of Biological Psychiatry, 2010

Objectives. The aim of this study was to compare patients ' preference for olanzapine orodispersi... more Objectives. The aim of this study was to compare patients ' preference for olanzapine orodispersible tablet (ODT) with oral conventional tablet (OCT). Methods. A 12-week randomized, crossover, multinational, open-label study was conducted to estimate the proportion of patients preferring ODT or OCT. Outpatients with stable schizophrenia on OCT monotherapy were randomly assigned 1:1 to ODT or OCT. Compliance and drug attitude were measured using the Drug Attitude Inventory (DAI-10) and Medication Adherence Form (MAF) scales; tolerability and safety by Association for Methodology and Documentation in Psychiatry (AMDP-5) questionnaire and adverse event summary. Results. A total of 175 patients answered a preference question: 106 (61%) preferred ODT and 48 (27%) preferred OCT (P Ͻ 0.001 adjusted for treatment sequence); 21 (12%) expressed no preference. There was no signifi cant change in DAI-10 with either formulation. MAF was above 75% in 94% vs. 93% of patients on ODC and OCT, respectively. Compliance as measured by tablet count was above 98% on both formulations. The adverse event profi les did not differ between formulations. Mean weight increase over 6 weeks on ODT was 0.8 kg and on OCT was 0.6 kg. Conclusions. Given the importance of patients ' preference for treatment planning and success, the ODT formulation should be routinely considered as a treatment option.

Expert Opinion on Pharmacotherapy, 2008

Our objective was to conduct a meta-analysis of therapeutic efficacy of pharmacological treatment... more Our objective was to conduct a meta-analysis of therapeutic efficacy of pharmacological treatment of adult ADHD based on data from controlled clinical trials. We used the search engines PubMed and Medline to identify relevant clinical trials. Short-term studies with double-blind parallel-group design were selected for the analysis. Altogether, we identified 11 trials that met the criteria, and investigated a total of 1991 subjects, 694 and 1297 of whom were treated with placebo or active medication, respectively. In order to pool efficacy data from studies with different characteristics, including different number of participants, different trial duration and measures of efficacy, the statistical effect sizes for each study had to be calculated. Our findings showed that the pooled effect size across all treatments was in the medium-to-high range (Cohen's d=0.65, p<0.0001 vs. placebo), and the effect size for stimulants (Cohen's d=0.67, p<0.0001 vs. placebo) was somewhat higher than for non-stimulant medications (Cohen's d=0.59, p<0.0001 vs. placebo). The current database of controlled trials for adult ADHD is relatively small, and does not include data for many of the potentially important agents. In addition, effect-size estimates for different classes of medications (i.e. stimulant and non-stimulant medications) were based on separate studies; head-to-head comparisons of various agents are severely lacking. Nonetheless, results of this meta-analysis across all ADHD medications in adult subjects demonstrated statistically significant and clinically robust improvement in symptom severity compared to placebo treatment.

European Neuropsychopharmacology, 2014

There is recognition that biomedical research into the causes of mental disorders and their treat... more There is recognition that biomedical research into the causes of mental disorders and their treatment needs to adopt new approaches to research. Novel biomedical techniques have advanced our understanding of how the brain develops and is shaped by behaviour and environment. This has led to the advent of stratified medicine, which translates advances in basic research by targeting aetiological mechanisms underlying mental disorder. The resulting increase in diagnostic precision and targeted treatments may provide a window of opportunity to address the large public health burden, and individual suffering associated with mental disorders. While mental health and mental disorders have significant representation in the "health, demographic change and wellbeing" challenge identified in Horizon 2020, the framework n

The lancet. Psychiatry, Jan 8, 2017

Just over 25 years have passed since the major sociopolitical changes in central and eastern Euro... more Just over 25 years have passed since the major sociopolitical changes in central and eastern Europe; our aim was to map and analyse the development of mental health-care practice for people with severe mental illnesses in this region since then. A scoping review was complemented by an expert survey in 24 countries. Mental health-care practice in the region differs greatly across as well as within individual countries. National policies often exist but reforms remain mostly in the realm of aspiration. Services are predominantly based in psychiatric hospitals. Decision making on resource allocation is not transparent, and full economic evaluations of complex interventions and rigorous epidemiological studies are lacking. Stigma seems to be higher than in other European countries, but consideration of human rights and user involvement are increasing. The region has seen respectable development, which happened because of grassroots initiatives supported by international organisations, r...