To explore tolerability, safety and treatment response of flexibly dosed paliperidone palmitate (PP) in adult non-acute schizophrenia patients previously unsuccessfully treated with oral antipsychotic monotherapy of risperidone (RIS), paliperidone ER (Pali ER), olanzapine (OLA), quetiapine (QUE) or aripiprazole (ARI).

International, prospective 6-month open-label study. Outcomes were response (≥20% improvement in Positive and Negative Syndrome Scale (PANSS) total score at endpoint), patient functioning (Personal and Social Performance scale (PSP)), treatment-emergent adverse events (TEAEs) and Extrapyramidal Symptom Rating Scale (ESRS).

Intent-to-treat population: n=191 (RIS), n=104 (Pali ER), n=87 (OLA), n=46 (ARI), n=44 (QUE). Patients presented some differences in baseline demographics, e.g. in age, years since diagnosis and BMI. Baseline mean PANSS total scores ranged from 74.7±14.9 (ARI) to 70.8±13.1 (QUE) and 70.8±15.1 (RIS). Between 67.4% (ARI) and 83.2% (RIS) of patients completed the study. At endpoint, 74% (RIS), 58% (Pali ER), 61% (OLA), 66% (QUE) and 52% (ARI) of patients had improved ≥20% in PANSS total score. Mean PSP improvement at endpoint was: 10.4±13.8 (RIS), 7.0±13.8 (Pali ER), 4.5±15.9 (OLA), 7.9±12.4 (QUE) and 3.9±13.2 (ARI); all p<0.05. TEAEs reported at least once in all subgroups were injection site pain, insomnia and psychotic disorder. Mean change in ESRS from baseline to endpoint was -1.2±3.5 (RIS), - 0.7±4.1 (Pali ER), -1.3±4.4 (OLA), -0.3±3.2 (QUE) and -0.6±3.4 (ARI; p<0.05 for all except QUE).

PP was well tolerated and associated with clinically relevant treatment response in patients previously unsuccessfully treated with oral atypical antipsychotic monotherapy, regardless of the medication that was switched.

Recent metaanalyses have reported conflicting results on the efficacy of long-acting compared to oral antipsychotics in the prevention of relapse in patients with schizophrenia.

2-year international randomized active controlled, open-label, rater-blinded study evaluating time to relapse, relapse rates, psychotic symptoms (PANSS) and treatment-emergent adverse events (TEAEs) in recently diagnosed patients with schizophrenia (≥1-5 years) treated with a monotherapy of paliperidone palmitate (PP) compared to investigators’ choice of oral antipsychotics (oAPs), i.e. aripiprazole, olanzapine, quetiapine, paliperidone ER, risperidone or haloperidol.

715 patients (58.4% male, mean age 32.5±10.4 years, 86.2% paranoid schizophrenia, no significant differences in baseline characteristics) entered the 2-year study period (352 PP, 363 oAPs). Time to relapse was significantly longer with PP compared to oAPs (mean±SE: 616±10.9 vs 603±13.1 days, p=0.019). Relapse rates were significantly lower with PP vs oAPs (14.8% vs 20.9%; p=0.032), reflecting a relative risk reduction of 29.2%. Reduction of psychotic symptoms in PANSS was significantly superior with PP at treatment day 8 (p=0.021) and showed a trend in favor of PP at endpoint (p=0.074). TEAEs reported in ≥5% in any group (PP vs oAPs) were weight increase (15.9% vs 17.4%), headache (11.1% vs 8.5%), insomnia (9.7% vs 8.0%), schizophrenia (8.2% vs 9.6%), nasopharyngitis (7.1% vs 5.0%), injection site pain (6.8% vs 0%), anxiety (5.7% vs 4.4%), tremor (5.1% vs 2.2%) and suicidal ideation (4.5% vs 5.5%).

In this randomized active controlled 2-year study PP was significantly delaying time to relapse and reducing relapse rates compared to investigators’ choice of oral APs.

This study explores tolerability, safety and treatment response of flexible doses of the atypical long-acting antipsychotic paliperidone palmitate (PP) in adult patients with an acute exacerbation of schizophrenia previously unsuccessfully treated with oral antipsychotics.

International prospective open-label 6-month study. Outcome parameters were change in Positive and Negative Syndrome Scale (PANSS) total score, Clinical Global Impression-Severity Scale (CGI-S), treatment-emergent adverse events (TEAEs) and weight change.

212 acute patients, 59.0% male, mean age 36.4 ±12.1 years, 85.4% paranoid schizophrenia were enrolled. 70.3% of patients completed the study. Most frequent reasons for early discontinuation were subject choice (9.4%), or an adverse event (9.0%). Recommended initiation regimen of PP (150 mg eq on day 1 and 100 mg eq on day 8) was administered in 92.9% of subjects. Mean baseline PANSS total score decreased from 98.5±20.1 as of day 8 of treatment to 67.4±24.0 at endpoint (mean change -31.0±28.97; 95% confidence interval [CI]-35.0;-27.1; p<0.0001). 66.7% of patients improved ≥30% in PANSS total score and percentage of patients rated markedly ill or worse in CGI-S decreased from 75.1% at baseline to 20.5% at endpoint. TEAEs reported in ≥5% were injection site pain (13.7%), insomnia (10.8%), psychotic disorder (10.4%), headache (6.1%) and anxiety (6.1%). Mean weight change at endpoint was 2.6±5.6 kg (95%CI 1.8; 3.4).

These data support results from previous randomized controlled studies that flexibly dosed paliperidone palmitate is well tolerated and associated with an early and clinically relevant treatment response in acute schizophrenia patients previously unsuccessfully treated with oral antipsychotics.

Negative, disorganized and depressive symptoms are among the major unmet needs in the treatment of patients with schizophrenia. The objective of this analysis was to explore the impact of flexibly dosed paliperidone palmitate (PP) on negative and depressive symptoms, disorganized thoughts, subjective well-being and treatment satisfaction in adult non-acute but symptomatic patients with schizophrenia previously unsuccessfully treated with oral antipsychotics.

International, prospective 6-month open-label multicenter study. Outcomes analyzed were changes from baseline to endpoint in negative symptoms, disorganized thoughts and anxiety/depression Marder factors of the Positive and Negative Syndrome Scale (PANSS), patient well-being (Subjective Well-Being with Neuroleptics, short version), and patient treatment satisfaction.

593 patients (intent-to-treat population), 63.1% male, mean age 38.4±11.8 years, 78.6% paranoid schizophrenia, were analyzed. 74.5% of patients completed the study. Mean baseline PANSS negative subscale scores (20.2±5.4) improved significantly by -3.5±5.4 points from baseline to endpoint (95% confidence interval [CI] -3.9;-3.0), the PANSS negative symptoms Marder factor score improved from 19.6±5.6 to 16.1±5.7 (95%CI of change -3.9;-3.1), and the disorganized thoughts Marder factor score improved from 16.2±4.4 to 13.9±4.6 (95%CI -2.6;-1.9). Similarly, the anxiety/depression Marder factor score improved from 9.3±3.1 to 7.6±3.1 (95%CI -2.0;-1.5, all p<0.0001). Subjective well-being (SWN-S) increased from 80.1±17.2 at baseline to 85.5±17.3 at endpoint (95%CI 4.0;6.7), and treatment satisfaction improved significantly from 55.3±19.6 to 63.9±22.8 (95%CI 6.4;11.0, both p<0.0001).

Paliperidone palmitate treatment of non-acute but symptomatic patients with schizophrenia showed significant and clinically relevant improvements in negative and depressive symptoms, disorganized thoughts, subjective well-being and patient treatment satisfaction.

To explore tolerability, safety and treatment response of flexibly dosed paliperidone palmitate (PP) in adult non-acute but symptomatic patients with schizophrenia previously unsuccessfully treated with risperidone long-acting injectable treatment (RLAT).

International, prospective 6-month open-label study. Major outcomes were clinical response (percentage of patients with ≥20% improvement in Positive and Negative Syndrome Scale (PANSS) total score at endpoint), functioning (Personal and Social Performance scale (PSP)), Extrapyramidal Symptom Rating Scale (ESRS), sleep quality, daytime drowsiness and treatment-emergent adverse events (TEAEs).

The intent-to-treat population comprised 56 patients (64.3% male, mean age 39.9±11.0 years, 71.4% paranoid schizophrenia). 71.4% of patients completed the 6-month study. Withdrawal of consent (8.9%) and adverse events (10.7%) were the most frequent reasons for early discontinuation. Mean PANSS baseline total score was 67.5±20.7 and decreased by -9.2 points at endpoint (95% confidence interval -15.0;-3.5, p<0.0001). At endpoint, 61.1% of patients had improved by ≥20% in PANSS total score. Patient functioning in PSP increased by 5.2±15.3 points (p=0.0163). Sleep quality and daytime drowsiness improved significantly (both p<0.0292). Extrapyramidal symptoms in ESRS significantly improved from 3.7±7.2 at baseline to 2.4±6.4 at endpoint (p=0.0011). TEAEs reported in ≥5% were psychotic disorder (10.7%), injection site pain, headache, schizophrenia, anxiety (7.1% each), constipation and somnolence (5.4% each). Mean body weight decreased by 0.9±4.5 kg from baseline to endpoint.

These data suggest that paliperidone palmitate is associated with a meaningful clinical response and functional improvement and is well tolerated with less EPS in non-acute, symptomatic schizophrenia patients previously unsuccessfully treated with RLAT.

To explore tolerability, safety and treatment response of flexibly dosed paliperidone palmitate (PP) in adult non-acute patients with schizophrenia previously unsuccessfully treated with the decanoate of haloperidol (Hal), flupentixol (Fpt), fluphenazine (Flu) or zuclopenthixol (Zuc).

International, prospective 6-month open-label study. Outcomes were clinical response (≥20% improvement in Positive and Negative Syndrome Scale (PANSS) total score), Personal and Social Performance scale (PSP), Extrapyramidal Symptom Rating Scale (ESRS) and treatment-emergent adverse events (TEAEs).

The intent-to-treat population comprised n=53 Hal, n=35 Fpt, n=44 Flu and n=42 Zuc patients. Mean age ranged from 42.1±10.7 [Zuc] to 44.4±9.4 years [Hal]), male gender from 57.1% [Zuc] to 69.8% [Hal]), and BMI from 27.3±5.9 [Hal] to 30.8±8.5 kg/m2 [Zuc]). Between 70.5% [Flu] and 85.7% [Fpt] of patients completed the study. Mean baseline PANSS total scores ranged from 73.7±14.1 [Fpt] to 75.7±13.2 [Hal]) and decreased significantly by -7.5±19.4 [Flu] to -10.6±21.5 points [Zuc] at endpoint (p<0.003 all subgroups). At endpoint, between 53.7% [Zuc] to 61.8% [Fpt] of patients had improved ≥20% in PANSS total score. Patient functioning (PSP) improved by 5.2±13.0 [Hal] to 6.4±15.2 points [Zuc] (all p≤0.0071). TEAEs reported at least once in all and in ≥5% in any subgroup were insomnia (max 11.5%), psychotic disorder (max 9.5%) and injection site pain (max 9.1% of subjects). Extrapyramidal symptoms in ESRS significantly improved from baseline to endpoint (all subgroups p<0.01).

Paliperidone palmitate was associated with a clinically meaningful treatment response and well tolerated in non-acute schizophrenia patients previously unsuccessfully treated with conventional depot antipsychotics.

Neuroleptic malignant syndrome (NMS) is a serious side effect of the antipsychotic, potentially life-threatening. The NMS is characterized by a distinctive clinical syndrome of mental status change, rigidity, fever, and dysautonomia. Even the newer atypical antipsychotics (AA), which are not classified accurately as neuroleptics, can cause NMS.

We report the clinical course of a NMS in a 37-year-old male with bipolar disorder. The clinical onset and the evolution are described.

The patient was treated with different AA drugs (risperidone and olanzapine), and after a dosage increase of olanzapine extrapyramidal symptoms appeared (muscular rigidity, hyperthermia, dystonia, tachycardia and profuse diaphoresis) and laboratory abnormalities (CK-NAC 21000U/L).

The patient is examined and evaluated by a internal medicine physician and moved to the Intensive Care Unit (ICU) where he started hydration using intravenous fluids, antibiotics (meropenem), benzodiazepines (diazepan) and dopamine agonist (bromocriptine). His admission in ICU was 13 days.

The pathogenesis of NMD in BD is poorly understood. Current theories are limited in their ability to explain all clinical manifestations. Although there is no diagnostic test for NMS, testing has a crucial role in the evaluation of patients with potential NMS. Typical laboratory abnormalities help to confirm the clinical diagnosis.

According to the literature reviewed, all classes of antipsychotics have been associated with neuroleptic malignant syndrome, including lowpotency neuroleptics, high potency neuroleptics and the newer atypical antipsychotics, so we must monitor patients who start or increase dose of atypical or typical antipsychotics.

There is a clear consensus that psychotherapy works. Simultaneously, there is considerable disagreement as to what makes psychotherapy work: specific techniques or common factors. However, this dichotomy of specific techniques and common factors is not justified. Conceptual considerations and empirical data rather suggest an integrative view.

The present study empirically analyses the relationships between specific techniques, common factors and the outcome of psychotherapy.

After each psychotherapy session the patients of a psychiatric outpatient clinic completed a questionnaire, which evaluated the implementation of common factors. Likewise, the therapists rated the techniques they had applied during the session on a technique questionnaire at the end of each session. In addition, measurements of patient characteristics as well as pre- and post-treatment assessments of their psychopathology, social functioning, resources, coping style and quality of life were accomplished. Hierarchical regression analyses (mixed models) were then performed to analyze the associations between techniques, common factors and outcome variables.

Results indicate that patterns of specific techniques are associated with the implementation of different common factors. In addition, specific associations of therapy techniques and common factors are related to distinct outcome variables.

The identification of the active therapeutic ingredients and work mechanisms facilitates the development of integrated personalized psychotherapeutic interventions, which are tailored to the particular problems, needs and resources of the individual patient. This would allow for moving away from delivering standardized treatment packages with different untested elements and, thereby, might enhance the effectiveness and efficient implementation of evidence-based psychotherapy approaches.

it is well established that adversities and GRIN2B genetic variants (encoding NMDAR GluN2B subunit) are independently associated with behavioral and cognitive impairments in childhood. However, a high proportion of children exposed to risk have good, long-term outcomes.

for the first time, we explored how environmental adversities and GRIN2B genetic variants influence children's cognitive abilities and behavioral problems.

we adopted a gene-by-environment interaction (GxE) approach, to identify children with an unfavorable developmental outcome with the potential of better informing the understanding of susceptibility to developmental disorders.

6 SNPs of GRIN2B were genotyped in 625 children aged 6-11 years from an Italian community-based sample. The interactive effect of GRIN2B variants with 4 measures of adversities (low socioeconomic status - SES, preterm delivery, maternal smoking, absence of breastfeeding) was investigated upon cognitive abilities (vocabulary, block design, forward/backward digit spans of Wechsler's Intelligence Scale, and Rey Figure test) and parents-rated behavioral problems (Child Behavior Checklist/6-18).

rs5796555 x gestational age interaction (p= .00145) influenced cognition, with lower IQ memory among children in the ‘A/A genotype and ≤ 36 gestational age’ group, compared to all other groups. Rs2268119 x SES interaction (p= .00008) influenced behavior, with more attention problems among children in the ‘either A/T or T/T genotype and low SES’ group, compared to all other groups.

GRIN2B targets children with the worst outcome in memory and attention functioning among children exposed to environmental adversities. Identification of children with the highest risk may prompt cost-effective preventive/treatment strategies.

Ostracism (social exclusion) has been found to be a remarkable stress factor to mentally ill people with difficulties in situations of social interaction. In an earlier study it was found that patients with borderline personality disorder (BPD) showed differences in oxytocin dysregulation by having lower oxytocin plasma levels during a social exclusion paradigm (Jobst et al., 2013, submitted). To our knowledge, this is the first study investigating neuroendocrinological changes of social exclusion in chronically depressed patients. Chronic depression (CD) is associated with poor social functioning and behavioral interpersonal problems which are considered to be based on the non-responsiveness of CD patients to environmental consequences.

To manipulate a situation of social exclusion we used the Cyberball Paradigm, a virtual ball tossing game which has been well validated and applied in numerous previous studies on the effects of social exclusion. 19 CD patients (according to DSM-IV) and 19 healthy controls matched for gender, age and education underwent repeated neuroendocrine measurements in a standardized laboratory setting during the Cyberball Paradigm. Assessments of psychological variables as well as measurements of oxytocin plasma levels were performed at baseline, 5 min, 15 min and 40 min after Cyberball.

As an association of interpersonal problems in BPD with oxytocin dysregulation has been found, we suggest differences in changes of oxytocin levels in a social exclusion situation in CD patients versus healthy subjects. The data will be presented and discussed in relation to specific interpersonal problems of patients suffering from CD.

Higher sustainability in outpatient mental health care is frequently demanded but hardly analyzed. Cooperation, burn out and job satisfaction do account as indicators for sustainability in health care systems. Knowing their status' and influencing factors among central players provides toeholds for more sustainability in outpatient mental health care.

1. 1. Evaluating the status quo of job satisfaction, burn out and cooperation among registered psychiatrist in Switzerland.

2. 2. Analyzing interactions between the three indicators.

A postal survey was conducted among all registered psychiatrists in the German speaking part of Switzerland (n=1.485) via the Swiss Medical Association containing standardized questionnaires concerning work satisfaction, burn out and cooperation in outpatient mental health care.

The response rate was 23.3%; 347 cases were included in further analyzes. A great range of quality and quantity of cooperation was found; respectively depending on the different stakeholders of outpatient mental health care. Overall, quality of cooperation was predominantly high while quantity of cooperation was comparatively low. Overall job satisfaction with was rather high, while burn out rates were rather low. High quality of cooperation proved to be the strongest and most significant factor for an increase of job satisfaction and a decrease of burn out risk. Further analyzes are in progress.

Concerning the role of psychiatrist, present data suggest a rather high sustainability of the Swiss outpatient health care system. Since high quality of cooperation seems to be a reinforcing factor, it should be a central target in developing sustainable mental health care concepts.

Internalized or self-stigma is known to affect engagement with treatment and long term outcomes in people with chronic mental illness. Little data exists regarding the incidence of internalized stigma in young people experiencing first-episode psychosis and there are no clearly proven interventions with which to address it in this age group.

To identify the extent of internalized stigma in young people with first-episode psychosis.

52 young people (mean age 21 years) attending an early intervention service in Wellington, New Zealand completed Internalized Stigma of Mental Illness (ISMI) scales at the start of a randomized controlled trial of a new narrative-based psychotherapeutic intervention. Mean total and subscale ISMI scores were compared with a previously studied older cohort of people with chronic mental illness.

Statistically significant differences in total and most subscale ISMI scores were identified between young people with first-episode psychosis and the older cohort of people with chronic mental illness.

Internalized stigma exists, but is less severe in young people with first-episode psychosis than older people with chronic mental illness. Potential reasons and implications will be discussed.

The aim of this presentation is to summarize the results of the published systematic reviews / meta-analyses of the randomized controlled trials that have investigated the effectiveness of medications for the treatment of obsessive compulsive disorder (OCD) in children/adolescents and adults and to present preliminary results from a new review study using network meta-analytical techniques

Medline, Cochrane database, and the register of controlled trials maintained by the Cochrane Collaboration Depression, Anxiety & Neurosis Group (CCDAN) were searched for relevant trials, systematic reviews and/or meta-analyses.

Regarding the new review study we were able to extract 103 pharmacological arms (preliminary results: 9 for Fluoxetine, 16 for Fluvoxamine, 11 for Paroxetine, 10 for Sertraline, 16 for Clomipramine, 7 for Citalopram / escitalopram, 2 for Venlafaxine, and 32 for Placebo) with a total number of 6572 patients randomized. The previous meta-analyses have confirmed the efficacy for all SSRIs and Clomipramine in all age groups while for other drugs further evidence is required. In the context of this presentation preliminary results of the relative efficacy of each drug, using network meta-analysis techniques will also be reported.

Several antidepressants have established their efficacy and acceptability for the management of non-resistant OCD. The major weakness of the literature so far is that head to head comparisons between antidepressants are few and therefore it is difficult to establish a clear hierarchy of the efficacy and acceptability of the various agents. This gap in the present literature will be filled by the present review.

Besides affective instability and identity diffusion, disturbances in social interactions are a core symptom of borderline personality disorder (BPD). Interpersonal problems in BPD have been suggested to be associated with oxytocin dysregulation. To directly address this hypothesis, we investigated oxytocin plasma levels during a social exclusion (ostracism) paradigm in female BPD patients.

Twenty-two female BPD patients (diagnosed according to DSM-IV) and twenty-one healthy controls matched for gender, age, and education underwent repeated neuroendocrine measurements in a standardized laboratory setting during the Cyberball paradigm, a virtual balltossing game that evokes a social exclusion situation. Emotional reactions were assessed and oxytocin and cortisol levels measured at baseline and 5, 15, and 40 min after Cyberball.

After social exclusion, oxytocin plasma levels were lower in BPD patients than in healthy controls, whereas cortisol levels did not differ between groups. BPD patients showed distinct differences in emotion regulation compared to healthy participants and reacted to social exclusion with an increase of other-focused negative emotions, particularly anger and contempt.

Our pilot study suggests that the oxytocin system shows a differential response to social exclusion in BPD patients compared to healthy controls. This difference may be related to the high rejection sensitivity of BPD patients and their difficulties in resolving social conflict.

The aim of this case study is to illustrate what role factors such as culture and migration history play for the course of mental illnesses. Methods We present a report on a male patient from Iraq, age 48, suffering from depression and chronicle pain syndrome. Stressful experiences such as the loss of his wife and daughter were the trigger for depressive episodes.

There are three main challenges with regard to treating patients with different that recently immigrated: (1) the language barrier, (2) cultural differences that complicate communication, and (3) the use of stereotypes. In order to optimize treatment it is necessary to consider the specific background of migration as well as the details of the migration history itself.

There are specific difficulties that hamper the treatment of migrants, namely cultural differences and communication barriers. Support from complementary health care is necessary to prevent further social isolation.

In the last decades the unethiological approach in clinical medicine is very frequent (the ‘medicine of consequences’, N. Ilankovic). Because the syndromological diagnoses and (relative) effective symptomatic therapy in clinical psychiatry, in most cases the therapeutic targets are only the phenomenology of behavioral disorders and the neurochemical, imunological and morphological consequences, without precise etiopathogenetic approach.

Researchers have found that both medical and psychiatric comorbidity is common in patients with psychiatric disorders, particularly in children, adolescents and in old age.

To schow how many psychotic disorders have real and detectable etiology, very frequently extracerebral origin.

Clinical and etiological analysis of data of all clinical laboratory and neuroimaging investigationes by 100 patients with psychotic disorders with schizophrenic and schizophreniform clinical pictures.

In most of patient (29%) the cause of psychotic episode was the substance abuse, in 25% extracerebral focal and systemic infection (inflammation), in 16% endocrin-metabolic disorders (extracerebral origin), in 11% brain damage, in 7% cerebrovascular disorders, and in 7% neurodevelopmental disorders.

In about 70% of our patients with schizophrenic and schizophreniform psychotic disorders the primary causes of illness were extracerabral. The real etiological approach and diagnosis in clinical psychiatry open the door to most targeted etiological therapy of psychotic and other mental disorders.

Attachment and companionship are fundamental basic needs of human beings and contribute the feeling of security and social affiliation. It is assumed that dysfunctional attachment behaviour in people with Borderline Personality Disorder leads to difficulties in the interpersonal contact. Unsecure and especially disorganized manners of attachment seem to be frequently represented by mentally ill people. In this study the release of oxytocin according to attachment relevant situations was investigated and attachment representations of people with BPD have been analysed.

In order to determine attachment representations of healthy people and of people with BPD we used the validated ‘Adult Attachment Projective’/ ‘AAP’ by George, West and Pettem (1999). The projective contains eight contour drawings of attachment relevant situations. The participant should make up a story of each picture, which was evaluated by its coherence, its content and the used defence mechanisms. Attachment representations of 30 patients with BPD were surveyed. Furthermore we measured the release of oxytocin evoked by an activation of the attachment system via the ‘AAP’ in 10 healthy people. Therefor blood drawings were performed at four different points of time.

Here, we present pilot data on oxytocin measures induced via the ‘AAP’. We could detect a decrease of oxytocin in healthy people caused by an activation of the attachment system. Moreover attachment representations of patients with BPD will be presented and discussed. These preliminary data could lead to further studies on a possible dysregulation of the attachment- and the oxytocin system of people with BPD.