[Medical continuity in the supply psychiatry before and after implementation of the new working hours act based on the example of the psychiatric department in the Danube hospital Vienna]. / Ärztliche Kontinuität in der Versorgungspsychiatrie vor und nach Einführung des Arbeitszeitgesetzes-Neu am Beispiel der psychiatrischen Abteilung des Donauspitals in Wien.

A successful and sustainable treatment of psychiatric patients is based on intensive relationship work. After the introduction of the new Working Hours Act the standards of evidence-based treatment are endangered. Using the data of the official working schedule of the Psychiatric Department of the Danube hospital in Vienna, before and after the introduction of the new Working Hours Act, we demonstrate a significant decrease of the medical consistency of the patient-related doctors. New approaches must be considered in order to solve this problem of quality.

[How do Psychiatric Hospitals in Austria Realise an Open Door Policy?] / Wie können psychiatrische Kliniken in Österreich vollständig offen geführt werden?

OBJECTIVE: Many psychiatric hospitals in Austria have an open door policy. We aimed to compare staffing levels, use of coercive measures, and beds per inhabitants between an Austrian and a German psychiatric hospital with partly locked doors. METHODS: Analysis of frequency of seclusion and restraint, aggressive incidents, police searches, availability of beds, and staffing levels in standardized counts. RESULTS: German wards were open 65 % of daytime, Austrian wards 100 %. In the German region, considerable part of hospital beds were located in day clinics and psychosomatic clinics. The percentage of all admissions subjected to coercion was considerably lower in Germany, but this did not apply to involuntary admissions. Police searches were comparable in frequency. Staffing levels of physicians and psychologists were similar, in Austria considerably more nurses were available. CONCLUSION: The results do not provide evidence that the open door policy in Austrian psychiatry is realized by use of other coercive measures. Possibly more nursing staff is important to open doors.

1st International Experts' Meeting on Agitation: Conclusions Regarding the Current and Ideal Management Paradigm of Agitation.

Agitation is a heterogeneous concept without a uniformly accepted definition, however, it is generally considered as a state of cognitive and motor hyperactivity characterized by excessive or inappropriate motor or verbal activity with marked emotional arousal. Not only the definition but also other aspects of agitated patients' care are still unsolved and need consensus and improvement. To help the discussion about agitation among experts and improve the identification, management, and treatment of agitation, the 1st International Experts' Meeting on Agitation was held in October 2016 in Madrid. It was attended by 20 experts from Europe and Latin America with broad experience in the clinical management of agitated patients. The present document summarizes the key conclusions of this meeting and highlights the need for an updated protocol of agitation management and treatment, the promotion of education and training among healthcare professionals to improve the care of these patients and the necessity to generate clinical data of agitated episodes.

Influence of intravenous administration of the antipsychotic drug benperidol on the QT interval.

A group effect is generally assumed regarding the prolongation of the QT interval through butyrophenone antipsychotics like haloperidol. Consequently intravenous administration of benperidol is seen critically notwithstanding sparse evidence; thus benperidol and haloperidol were compared regarding their cardiac risk of prolonging the QT interval when administered intravenously for acute sedation of psychotic patients. The QT interval was measured by a 12-lead ECG. For the correction of QT values Bazett's formula was used. The resulting QTc intervals of the benperidol and the haloperidol group were compared using Mann-Whitney U-test. Our data provide statistical evidence for benperidol being less prone to cause QTc prolongation than haloperidol (p = 0.049). The results of our study indicate a more favourable risk profile of benperidol compared to haloperidol regarding QTc prolongation when administered intravenously.

[QTc prolongation induced by intravenous sedation with Haloperidol, Prothipendyl and Lorazepam]. / QTc Veränderungen bei intravenöser Akutsedierung mit Haloperidol, Prothipendyl und Lorazepam.

OBJECTIVE: Specific sedation of acute psychotic patients with iv Haloperidol has been repeatedly criticized due to its cardiac risk on the basis of QTc prolongation, cumulating in the fact that iv application is no longer recommended according to the producer. Since Haloperidol still provides the only iv formulation of a high potency neuroleptic medication, and iv application offers some crucial advantages over other forms of application, we wanted to objectify QTc prolongation of Haloperidol iv as well as QTc prolongation of Prothipendyl iv, a low potency neuroleptic medication for unspecific sedation. METHODS: In our department all treatments with Haloperidol and Prothipendyl iv are ECG monitored and documented following an appointed guideline. Over 3 years all treatments according to this scheme and additionally treatments with Lorazepam iv have been analyzed regarding QTc prolongation. Non-parametric tests have been applied due to missing normal distribution of the data. RESULTS: 99 patients have been included in the survey. According to the iv medication applied patients have been divided into different subgroups. A significant QTc prolongation compared to the Lorazepam control group could be seen in the Haloperidol/Prothipendyl combination group as well as in the Prothipendyl monotherapy group, but not in the haloperidol monotherapy group. When patients were included, who additionally had received Lorazepam, results did not differ essentially with the exception that the Haloperidol/Prothipendyl combination had a significant greater prolongation than the Haloperidol group. CONCLUSIONS: Our data proves the well known fact that Haloperidol iv causes a pronounced QTc prolongation. However QTc prolongation by iv Prothipendyl is still more pronounced according to our data. Most potent in producing a QTc prolongation proved a combination of Prothipendyl and Haloperidol, a fact that most likely depicts a dose effect. Since we assume, that there will be continuing need for iv medication with Haloperidol and Prothipendyl in the future, due to lack of arguable alternatives, we recommend safety measures like ECG monitoring not only for Haloperidol, but too for unspecific sedation with iv Prothipendyl.

Combined analysis of 635 patients confirms an age-related association of the serotonin 2A receptor gene with tardive dyskinesia and specificity for the non-orofacial subtype.

Tardive dyskinesia (TD) is an important limiting factor in the use of typical antipsychotic drugs. Genetic variability in the serotonin 2A (5-HT(2A)) receptor may influence risk for TD but the results of prior studies are not confirmatory. The objective of this study was to determine association of T102C and His452Tyr polymorphisms in the 5-HT(2A) receptor gene (HTR(2A)) with TD in a large, multicentre patient sample. The design employed case-control analysis controlling for possible confounders using pooled, original data from published and available unpublished samples and employing logistic regression, analysis of variance and meta-analysis. The study sample consisted of 635 patients with schizophrenia or schizoaffective disorder (256 with TD and 379 without TD) drawn from five research centres, divided into six groups based on population origin. The main outcome measure was association of a categorical diagnosis of TD based on the Research Diagnostic Criteria for TD with HTR(2A) T102C and His452Tyr genotypes and haplotypes. The findings indicate significant association of TD with HTR(2A) T102C genotype (p=0.002) over and above the effect of population group, also when controlling for age and gender (p=0.0008), but not with His452Tyr genotype. The T102C genotype was significantly associated with TD in older (>median age 47 yr, p=0.002) but not younger patients and in patients with non-orofacial (limb-truncal) (p=0.001) but not orofacial TD. By meta-analysis the Mantel-Haenszel (M-H) pooled odds ratio (OR) across all the available data was 1.64. A T102C-His452Tyr haplotype was significantly associated with TD (p=0.0008). These findings confirm that genetic variability in HTR(2A) contributes a small but significant degree of risk for the expression of TD, particularly in older patients and specifically for the non-orofacial (limb-truncal) type. Together with other genetic variants associated with TD the findings could be used to assess risk in patients who are candidates for treatment with typical antipsychotic medications.

Pharmacogenetics of dopamine receptors and response to antipsychotic drugs in schizophrenia--an update.

A considerable number of pharmacogenetic studies have been performed in recent years to define the association of antipsychotic medication response with dopamine receptor polymorphisms and, despite contradictory results, decisive trends have emerged. For the dopamine D2 receptor (DRD2), a trend toward an association with favorable response seems to emerge for the -141C Ins allele of the DRD2 -141C Ins/Del polymorphism and the A1 allele of the Taq1A polymorphism. In the case of the D3 receptor, the Ser9Gly polymorphism has been extensively investigated and a pattern of association is seen between the Ser9 allele and a response to typical antipsychotics, and between the Gly9 allele and a response to atypical antipsychotics. For the D4 receptor, no convincing association results have been reported to date. These trends are discussed with regard to methodological directives and functional implications.

Pharmacogenetics of tardive dyskinesia: combined analysis of 780 patients supports association with dopamine D3 receptor gene Ser9Gly polymorphism.

Variability among individuals in their therapeutic response to psychotropic drugs and in susceptibility to adverse effects is considerable. Pharmacogenetics addresses the contribution of genetic factors to this variability. An important focus of interest in pharmacogenetics has been on candidate genes that play a role in susceptibility to the antipsychotic drug-induced adverse effect, tardive dyskinesia (TD). Four published studies have reported an association between a serine (ser) to glycine (gly) polymorphism in exon 1 of the dopamine D3 receptor gene (DRD3) and TD; three failed to replicate this finding and one found an insignificant trend. We examined the association in a pooled sample of 780 patients (317 with TD and 463 without TD) drawn from 6 research centers, who were divided into 8 groups based on their population origin. The analysis employed stepwise logistic regression so as to allow confounding effects of group, age, and gender to be taken into account. TD was significantly associated with DRD3 gly allele carrier status (x(2)=4.46, df 1, p =.04) and with DRD3 genotype (x(2)=6.62, df 2, p =.04) over and above the effect of group. Similar positive effects were observed when controlling for age and gender (x(2)=5.02, df 1, p =.02 for gly allele carrier status; x(2) = 7.51, df 2, p =.002 for genotype). Examining abnormal involuntary movement scores as a continuous variable, we found that patients homozygous for the gly allele had significantly higher scores than ser-gly heterozygotes (p =.006) or ser-ser homozygotes (p <.0001). We also performed a meta-analysis that included, besides the groups in the combined analysis, three other published studies on DRD3 and TD. The Mantel-Haenszel pooled odds ratio for DRD3 gly allele carrier status increasing susceptibility to TD was 1.33 (95% CI 1.04-1.70, p =.02); the cumulative pooled estimate showed an odds ratio of 1.52 (95% CI 1.08-1.68, p <.0001). These findings support a small but significant contribution of the DRD3 ser9gly polymorphism to TD susceptibility that is demonstrable over and above population effects and the effect of age and gender on the phenotype.