Genetics-Based Population Pharmacokinetics and Pharmacodynamics of Risperidone in a Psychiatric Cohort.

BACKGROUND: High interindividual variability in plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, may lead to suboptimal drug concentration. OBJECTIVE: Using a population pharmacokinetic approach, we aimed to characterize the genetic and non-genetic sources of variability affecting risperidone and 9-hydroxyrisperidone pharmacokinetics, and relate them to common side effects. METHODS: Overall, 150 psychiatric patients (178 observations) treated with risperidone were genotyped for common polymorphisms in NR1/2, POR, PPARα, ABCB1, CYP2D6 and CYP3A genes. Plasma risperidone and 9-hydroxyrisperidone were measured, and clinical data and common clinical chemistry parameters were collected. Drug and metabolite concentrations were analyzed using non-linear mixed effect modeling (NONMEM(®)). Correlations between trough concentrations of the active moiety (risperidone plus 9-hydroxyrisperidone) and common side effects were assessed using logistic regression and linear mixed modeling. RESULTS: The cytochrome P450 (CYP) 2D6 phenotype explained 52 % of interindividual variability in risperidone pharmacokinetics. The area under the concentration-time curve (AUC) of the active moiety was found to be 28 % higher in CYP2D6 poor metabolizers compared with intermediate, extensive and ultrarapid metabolizers. No other genetic markers were found to significantly affect risperidone concentrations. 9-hydroxyrisperidone elimination was decreased by 26 % with doubling of age. A correlation between trough predicted concentration of the active moiety and neurologic symptoms was found (p = 0.03), suggesting that a concentration >40 ng/mL should be targeted only in cases of insufficient, or absence of, response. CONCLUSIONS: Genetic polymorphisms of CYP2D6 play an important role in risperidone, 9-hydroxyrisperidone and active moiety plasma concentration variability, which were associated with common side effects. These results highlight the importance of a personalized dosage adjustment during risperidone treatment.

Evaluation du risque de récidive dans les expertises pénales: quels outils? Quets indicateurs? Quelles pratiques [Risk assessment in forensic psychiatric reports: what kind assessment instrument? What indicator? What practical?].

Here we present results of studies conducted by the Research Unit of Legal Psychiatry and Psychology of Lausanne about risk assessment and protective factors in the evaluation of violence recidivism. It aims to help experts in considering the relevance and use of tools at their disposal. Particular attention is given to the significance of protective factors and impulsive dimensions, as to the inter-raters process that leads to the final deliberations.

A common cognitive, psychiatric, and dysmorphic phenotype in carriers of NRXN1 deletion

Deletions in the 2p16.3 region that includes the neurexin (NRXN1) gene are associated with intellectual disability and various psychiatric disorders, in particular, autism and schizophrenia. We present three unrelated patients, two adults and one child, in whom we identified an intragenic 2p16.3 deletion within the NRXN1 gene using an oligonucleotide comparative genomic hybridization array. The three patients presented dual diagnosis that consisted of mild intellectual disability and autism and bipolar disorder. Also, they all shared a dysmorphic phenotype characterized by a long face, deep set eyes, and prominent premaxilla. Genetic analysis of family members showed two inherited deletions. A comprehensive neuropsychological examination of the 2p16.3 deletion carriers revealed the same phenotype, characterized by anxiety disorder, borderline intelligence, and dysexecutive syndrome. The cognitive pattern of dysexecutive syndrome with poor working memory and reduced attention switching, mental flexibility, and verbal fluency was the same than those of the adult probands. We suggest that in addition to intellectual disability and psychiatric disease, NRXN1 deletion is a risk factor for a characteristic cognitive and dysmorphic profile. The new cognitive phenotype found in the 2p16.3 deletion carriers suggests that 2p16.3 deletions might have a wide variable expressivity instead of incomplete penetrance

The Changing Face of Psychiatric Nursing –Care or Control?

This report has been written as part of the project “Toward improved quality – developing nurse’s continuing vocational training in hospitals and inpatient units”. Its overall goal is to ensure high quality, ethically appropriate and therapeutically effective interventions to enable nurses to manage distressed and disturbed patients in European psychiatric hospitals and inpatient units. In this large-scale, multinational projects there are all together six European countries involved: Finland, Ireland, England, Portugal, Italy and Lithuania. The project work plan were during autumn 2006 and spring 2007. The content of this publication was produced in the first stage of the project aiming to collect the preliminary source material for the project. The literature review was carried out in the project stage, providing the groundwork for the next steps for the project. This project aims to develop an interactive multinational portal with training material. Therefore, it is important to share an understanding of basic information, psychiatric nurse’s continuing vocational education, laws and ethical codes and patient restriction used in mental health care. In this publication, the purpose of the material produced here is to understand nurses’ educational need related to vocational continuing education and to be used in further project stages as an empirical data collection. The data were collected as a preliminary source material for latter phases where nurse’s perceptions of the current practice, nurse’s attitudes to mental illness, prevalence of use of seclusion room and existing and desired vocational training provision will be collected in six different European countries. The following organisations are involved in this project: University of Turku, Dublin City University, St. Vincent Hospital, National Council for the Professional Development of Nursing and Midwifery, University of Padova, Klaipeda College - Health Faculty, Klaipeda Psychiatric Hospital, Escola Superior de Enfermagem de Lisboa, Centro Hospitalar Psiquiátrico de Lisboa, Omnia Vocational Institution the Espoo Region, Kellokoski psychiatric hospital, Hyvinkää hospital area, Pirkanmaa Hospital District, Kingston University & St. George’s Medical School and South West London & St. George’s Mental Health NHS Trust. A wide variety of different countries, organisations and individuals in this project give us a strong confidence that theoretical, practical, ethical and political issues around the topic of interest will be taken account during this project lifetime. We are aware the content of this book will be partially outdated almost as soon as it has been published. We still hope that this publication will encourage nurses and different professions working in mental health care field to have a basic understanding of similarities and differences between different European countries related in mental health care. We also hope that this publication will inspirate and motivate nurses in maintaining and developing the quality of psychiatric care in Europe.

Subtypes of adolescents with substance use disorders and psychiatric comorbidity using cluster and discriminant analysis of MMPI-A profiles

The main aim of this study was to replicate and extend previous results on subtypes of adolescents with substance use disorders (SUD), according to their Minnesota Multiphasic Personality Inventory for adolescents (MMPI-A) profiles. Sixty patients with SUD and psychiatric comorbidity (41.7% male, mean age = 15.9 years old) completed the MMPI-A, the Teen Addiction Severity Index (T-ASI), the Child Behaviour Checklist (CBCL), and were interviewed in order to determine DSMIV diagnoses and level of substance use. Mean MMPI-A personality profile showed moderate peaks in Psychopathic Deviate, Depression and Hysteria scales. Hierarchical cluster analysis revealed four profiles (acting-out, 35% of the sample; disorganized-conflictive, 15%; normative-impulsive, 15%; and deceptive-concealed, 35%). External correlates were found between cluster 1, CBCL externalizing symptoms at a clinical level and conduct disorders, and between cluster 2 and mixed CBCL internalized/externalized symptoms at a clinical level. Discriminant analysis showed that Depression, Psychopathic Deviate and Psychasthenia MMPI-A scales correctly classified 90% of the patients into the clusters obtained.

Reciprocal Effects on Neurocognitive and Metabolic Phenotypes in Mouse Models of 16p11.2 Deletion and Duplication Syndromes.

The 16p11.2 600 kb BP4-BP5 deletion and duplication syndromes have been associated with developmental delay; autism spectrum disorders; and reciprocal effects on the body mass index, head circumference and brain volumes. Here, we explored these relationships using novel engineered mouse models carrying a deletion (Del/+) or a duplication (Dup/+) of the Sult1a1-Spn region homologous to the human 16p11.2 BP4-BP5 locus. On a C57BL/6N inbred genetic background, Del/+ mice exhibited reduced weight and impaired adipogenesis, hyperactivity, repetitive behaviors, and recognition memory deficits. In contrast, Dup/+ mice showed largely opposite phenotypes. On a F1 C57BL/6N × C3B hybrid genetic background, we also observed alterations in social interaction in the Del/+ and the Dup/+ animals, with other robust phenotypes affecting recognition memory and weight. To explore the dosage effect of the 16p11.2 genes on metabolism, Del/+ and Dup/+ models were challenged with high fat and high sugar diet, which revealed opposite energy imbalance. Transcriptomic analysis revealed that the majority of the genes located in the Sult1a1-Spn region were sensitive to dosage with a major effect on several pathways associated with neurocognitive and metabolic phenotypes. Whereas the behavioral consequence of the 16p11 region genetic dosage was similar in mice and humans with activity and memory alterations, the metabolic defects were opposite: adult Del/+ mice are lean in comparison to the human obese phenotype and the Dup/+ mice are overweight in comparison to the human underweight phenotype. Together, these data indicate that the dosage imbalance at the 16p11.2 locus perturbs the expression of modifiers outside the CNV that can modulate the penetrance, expressivity and direction of effects in both humans and mice.

Acceptance and Use of Information Technology among Nurses in Psychiatric Hospitals

Hoitajien informaatioteknologian hyväksyntä ja käyttö psykiatrisissa sairaaloissa Informaatioteknologian (IT) käyttö ei ole ollut kovin merkittävässä roolissa psykiatrisessa hoitotyössä, vaikka IT sovellusten on todettu vaikuttaneen radikaalisti terveydenhuollon palveluihin ja hoitohenkilökunnan työprosesseihin viime vuosina. Tämän tutkimuksen tavoitteena on kuvata psykiatrisessa hoitotyössä toimivan hoitohenkilökunnan informaatioteknologian hyväksyntää ja käyttöä ja luoda suositus, jonka avulla on mahdollista tukea näitä asioita psykiatrisissa sairaaloissa. Tutkimus koostuu viidestä osatutkimuksesta, joissa on hyödynnetty sekä tilastollisia että laadullisia tutkimusmetodeja. Tutkimusaineistot on kerätty yhdeksän akuuttipsykiatrian osaston hoitohenkilökunnan keskuudessa vuosien 2003-2006 aikana. Technology Acceptance Model (TAM) –teoriaa on hyödynnetty jäsentämään tutkimusprosessia sekä syventämään ymmärrystä saaduista tutkimustuloksista. Tutkimus osoitti kahdeksan keskeistä tekijää, jotka saattavat tukea psykiatrisessa sairaalassa toimivien hoitajien tietoteknologiasovellusten hyväksyntää ja hyödyntämistä, kun nämä tekijät otetaan huomioon uusia sovelluksia käyttöönotettaessa. Tekijät jakautuivat kahteen ryhmään; ulkoiset tekijät (resurssien suuntaaminen, yhteistyö, tietokonetaidot, IT koulutus, sovelluksen käyttöön liittyvä harjoittelu, potilas-hoitaja suhde), sekä käytön helppous ja sovelluksen käytettävyys (käytön ohjeistus, käytettävyyden varmistaminen). TAM teoria todettiin käyttökelpoiseksi tulosten tulkinnassa. Kehitetty suositus sisältää ne toimenpiteet, joiden avulla on mahdollista tukea sekä organisaation johdon että hoitohenkilökunnan sitoutumista ja tätä kautta varmistaa uuden sovelluksen hyväksyntä ja käyttö hoitotyössä. Suositusta on mahdollista hyödyntää käytännössä kun uusia tietojärjestelmiä implementoidaan käyttöön psykiatrisissa sairaaloissa.

Personal Liberty in Psychiatric Care - Towards Service User Involvement

This study explores personal liberty in psychiatric care from a service user involvement perspective. The data were collected in four phases during the period 2000-2006 in psychiatric settings in Finland. Firstly, patient satisfaction and factors associated with user involvement were studied (n = 313). Secondly, patients’ experiences of deprivation of their liberty were explored (n = 51). Thirdly, an overview on patients’ options for lodging complaints was conducted, and all complaints (n = 4645) lodged in Finland from 2000 to 2004 were examined. Fourthly, the effects of different patient education methods on inpatients’ experiences of deprivation of liberty were tested (n = 311). It emerged that patients were quite satisfied, but reported dissatisfaction in restrictions, compulsory care and information dissemination. Patients experienced restrictions on leaving the ward and on communication, confiscation of property and coercive measures as deprivation of liberty. Patients’ experienced these interventions to be negative. In Finland, the patient complaint process is complicated and not easily accessible. In general, patient complaints increased considerably in Finland during the study period. In psychiatric care the number of complaints was quite stable and complaints led more seldom to consequences. An Internet-based patient education system was equivalent with traditional education and treatment as usual in supporting personal liberty during hospital care. This dissertation provides new information about the realization of patients' rights in psychiatric care. In order to improve patients' involvement, systematic methods to increase personal liberty during care need to be developed, the procedures for patients lodging complaints should be simplified, and patients' access to information needs to be ensured using multiple methods.

Predictors of psychiatric hospitalization during 6 months of maintenance treatment with olanzapine long-acting injection: post hoc analysis of a randomized, double-blind study.

BACKGROUND: Hospitalization is a costly and distressing event associated with relapse during schizophrenia treatment. No information is available on the predictors of psychiatric hospitalization during maintenance treatment with olanzapine long-acting injection (olanzapine-LAI) or how the risk of hospitalization differs between olanzapine-LAI and oral olanzapine. This study aimed to identify the predictors of psychiatric hospitalization during maintenance treatment with olanzapine-LAI and assessed four parameters: hospitalization prevalence, incidence rate, duration, and the time to first hospitalization. Olanzapine-LAI was also compared with a sub-therapeutic dose of olanzapine-LAI and with oral olanzapine. METHODS: This was a post hoc exploratory analysis of data from a randomized, double-blind study comparing the safety and efficacy of olanzapine-LAI (pooled active depot groups: 405 mg/4 weeks, 300 mg/2 weeks, and 150 mg/2 weeks) with oral olanzapine and sub-therapeutic olanzapine-LAI (45 mg/4 weeks) during 6 months' maintenance treatment of clinically stable schizophrenia outpatients (n=1064). The four psychiatric hospitalization parameters were analyzed for each treatment group. Within the olanzapine-LAI group, patients with and without hospitalization were compared on baseline characteristics. Logistic regression and Cox's proportional hazards models were used to identify the best predictors of hospitalization. Comparisons between the treatment groups employed descriptive statistics, the Kaplan-Meier estimator and Cox's proportional hazards models. RESULTS: Psychiatric hospitalization was best predicted by suicide threats in the 12 months before baseline and by prior hospitalization. Compared with sub-therapeutic olanzapine-LAI, olanzapine-LAI was associated with a significantly lower hospitalization rate (5.2% versus 11.1%, p < 0.01), a lower mean number of hospitalizations (0.1 versus 0.2, p = 0.01), a shorter mean duration of hospitalization (1.5 days versus 2.9 days, p < 0.01), and a similar median time to first hospitalization (35 versus 60 days, p = 0.48). Olanzapine-LAI did not differ significantly from oral olanzapine on the studied hospitalization parameters. CONCLUSIONS: In clinically stable schizophrenia outpatients receiving olanzapine-LAI maintenance treatment, psychiatric hospitalization was best predicted by a history of suicide threats and prior psychiatric hospitalization. Olanzapine-LAI was associated with a significantly lower incidence of psychiatric hospitalization and shorter duration of hospitalization compared with sub-therapeutic olanzapine-LAI. Olanzapine-LAI did not differ significantly from oral olanzapine on hospitalization parameters.

Improving Quality of Life of Patients With Schizophrenia In Acute Psychiatric Wards

The overall goal of this study was to identify means by which the quality of life (QoL) of patients with schizophrenia could be improved in acute psychiatric wards. First, subjective QoL of patients (n=35) was explored. Second, two different QoL instruments (EuroQoL-5D, EQ-5D; Quality of Life Enjoyment and Satisfaction Questionnaire Short Form, Q-LES-Q SF) were examined. Third, patients’ (n=35) and nurses’ (n=29) perceptions of nursing interventions to support patients’ QoL were examined. Fourth, the effect of three different patient education methods on patients’ QoL (n=311) was compared. The data were collected during the period 2005-2007. Patients named health, family, leisure activities, work or study, and social relationships most frequently as their important QoL areas. It emerged that patients’ QoL was impaired. Examination of two QoL instruments showed that the EQ-5D has moderate and the Q-LES-Q SF good internal consistency. Moreover, both instruments proved to be reasonably valid and feasible for use with patients with schizophrenia. Altogether six nursing interventions which nurses use to support patients’ QoL, and which should be further developed were identified from nurses’ descriptions: interventions related to care planning, empowering interventions, social interventions, activating interventions, security interventions, and interventions to support physical health. Evaluation of different patient education methods showed that patients’ QoL improved significantly during follow-up. No significant differences between groups were found. In light of the findings it is recommended to assess QoL of patients with schizophrenia as a basis for care planning and care evaluation in clinical settings. Valid and feasible instruments should be used in this assessment. Moreover, it is recommend that nursing interventions should be further developed to better improve patients’ QoL.

Patient Seclusion and Restraint Practices in Psychiatric Hospitals - Towards Evidence Based Clinical Nursing

The overall goal of this study was to support evidence based clinical nursing regarding patient seclusion and restraint practices. This was done by ensuring professional competence through innovative learning methods. The data were collected in three phases between March 2007 and May 2009 on acute psychiatric wards. Firstly, psychiatric inpatients’ experiences and suggestions for seclusion and restraint practices were explored (n=30). Secondly, nursing and medical personnel’s perceptions of seclusion and restraint practices were explored (n=27). Thirdly, the impacts of a continuing vocational eLearning course on nurses’ professional competence was evaluated (n=158). Patients’ perspectives received insufficient attention during the seclusion and restraint process. Improvements and alternatives to seclusion and restraint as suggested by the patients focused on essential parts of clinical nursing, but were not extensively adopted. Also nursing and medical personnel thought that patients’ subjective perspective received little attention. Personnel proposed a number of alternatives to seclusion and restraint, and they expressed a need for education and support to adopt these in clinical nursing. Evaluation of impacts of eLearning course on nurses’ professional competence showed no statistical differences between an eLearning group and an education-as-usual group. This dissertation provides evidence based knowledge about the realization of seclusion and restraint practices and the impacts of eLearning course on nurses’ professional competence in psychiatric hospitals. In order to improve clinical nursing the patient perspective must be accentuated. To ensure personnel’s professional competence, there is a need for written clinical guidelines, education and support. Continuing vocational education should bring together written clinical guidelines, ethical and legal issues and the support for personnel. To achieve the ambitious goal of such integration, achievable and affordable educational programmes are required. This, in turn, yields a call for innovative learning methods.

Adoption of information technology based patient education in psychiatric nursing

The overall goal of the study was to describe adoption of information technology (IT)-based patient education (PE) developed for patients and nurses use in psychiatric nursing. The data were collected in three phases during the period 2000-2006 in a variety of psychiatric settings in Finland. Firstly, the development process of IT-based PE for patients with schizophrenia spectrum psychosis was described. Secondly, nurses’ adoption of IT-based PE and the variables explaining adoption were demonstrated. Moreover, use of daily IT-based PE in clinical practice and factors associated with use were identified and described. And thirdly, nurses’ experiences of the IT-based PE after one year clinical use were evaluated. IT-based PE program was developed in several stages based on users’ needs and it included information and multimedia applications. Altogether, almost 500 IT-based PE sessions were carried out by the nurses on the study wards and revealed nurses’ activity in educating patients using IT to vary and depend on the hospital in which they worked. Almost 80% of all the possible IT-based PE sessions involved 93 patients and 83 nurses. Less than 2% of the IT-based PE sessions were interrupted and less than 10% suffered disturbances due to the patients or external causes. Moreover, the patients whose education took more days had poorer mental status than those whose education was carried out over a shorter period. After a year’s experience, advantages and disadvantages were described by the nurses for both patients and nurses of the IT-based PE. IT-based PE can be used even on closed acute psychiatric wards with patients with serious mental health disorders. However, technology adoption requires time, and therefore, it must fit in with clinical practice. Collaboration between users and developers is needed when developing user-centered methods in the area of mental health services. Moreover, it is important to understand factors that affect IT adoption in healthcare settings. IT-based PE is one option in interactive and co-operative health care practice between patients and nurses. Therefore the staff should begin to refer patients to established, credible and well-maintained Internet sites that provide information on common psychological problems. Even if every nurse should be trained and engaged to carry out IT-based PE, by targeting the training especially for the most active nurses aids them to support the less active ones. Adoption should also be understood from a perspective that includes aspects related to the context where it is implemented and examine how and in what circumstances it works.

Aggression and its Management in Adolescent Forensic Psychiatric Care

The overall goal of this study was to explore and identify good aggression management methods and on that basis to produce recommendations for aggression management in the adolescent forensic setting. The study was conducted in three phases. In Phase I, staff’s (n = 58) perception of adolescent aggressive behaviour and methods to manage it was examined. In Phase II, staff’s (n = 30) perception of treatment settings and treatment interventions available were studied. In Phase III, the effectiveness of an aggression management programme was evaluated. The data were collected during the period 2004-2007. Participants perceived adolescent aggressive behaviour in a similar way and described aggressive behaviour as being a comprehensible phenomenon. Management methods used to control aggressive situations were alike, although the practical solutions varied between the study units, especially regarding coercive methods. Staff members proposed more time and better opportunities to discuss and evaluate the aggression situation in order to improve the methods used. The treatment settings were similar in studied forensic units and interventions were primarily focused on psychological aspects, including management of aggressive behavior. A comprehensive aggression management programme proved to be effective in decreasing incidents of violence. The use of coercive methods in aggression situations decreased and injuries to the staff became less frequent. If staff members intend to apply high quality management methods in aggression situations they have to share a consistent understanding of aggressive behaviour and need to be aware of the various methods available. In addition, they should learn more about assessment methods in order to improve aggression management. International comparison of aggression, methods for managing it and service provision creates a starting point for developing equal care provision and realization within and between European countries.