To identify potential predictors of response to sertindole in patients with schizophrenia.

This twelve-month open-label study assessed the safety and efficacy of sertindole doses (4-24mg) in US patients with schizophrenia. Cox's regression analysis was applied to determine the effects of variables on time to sustained response (both CGI-S <=3 and CGI-I <=2, sustained for at least 8 weeks) in 358 patients.

125 patients achieved sustained response. Several factors appear to influence rate of response; amongst these are: treatment with antipsychotic medication before first diagnosis, severity of illness, ECT treatment, drug abuse history and patient weight. Treatment with antipsychotic medication before first diagnosis of schizophrenia increased the response rate, compared with treatment-naive patients. Mildly or moderately ill patients were more likely than more severely ill patients to respond to treatment with sertindole. Patients who never received ECT showed a higher rate of response to sertindole than those who received 1-5 courses of treatment. Patients with at least 6 courses showed a similar response to those who received none. Patients with no history of drug abuse were more likely to respond to sertindole, than patients who had a history of drug abuse. The response to sertindole is influenced by patient weight: for example, a patient weighing 150kg was more likely to respond than a patient weighing 75kg.

A prognostic index could be calculated based on these factors to predict the response of individual patients to treatment with sertindole.

To assess cross-sectional remission of schizophrenia symptoms in patients treated with quetiapine or haloperidol.

Retrospective analyses were conducted on ITT data from all relevant randomised, double-blind studies in the AstraZeneca clinical trial database: a 6-week fixed-dose study (5077IL/0013; Arvanitis et al, Biol Psychiatry 1997;42:233-246); an 8-week fixed-dose study (5077IL/0052; Emsley et al, Int Clin Psychopharmacol 2000;15:121-131); a 6-week flexible-dose study (5077IL/0014; Copolov et al, Psychol Med 2000;30:95-105); a 52-week flexible-dose study (5077IL/0050; Jones and Brecher, Eur Psychiatry 2006;21:S91), of which 12-week data were included in the analysis. Patients in these studies had acute schizophrenia (CGI-S≥4, BPRS≥27 or PANSS≥60) or were partial responders to previous antipsychotics. Cross-sectional remission criteria were as defined by Andreasen et al (Am J Psychiatry 2005;162:441-449), apart from duration (6-12 week data were used). An alternative definition of remission was the proportion of patients with CGI-S≤3.

Data from 791 quetiapine- and 586 haloperidol-treated patients were analysed. Mean quetiapine/haloperidol doses in studies 0013, 0014, 0050 and 0052 were: 379/12, 455/8, 431/13 and 600/20 mg/day. In three studies (0013, 0014 and 0050), cross-sectional remission (modified Andreasen criteria) was similar for quetiapine (13-32%) and haloperidol (14-32%). CGI-S remission rates were also comparable (quetiapine 23-40%; haloperidol 24-43%) in these studies. In study 0052, more quetiapine patients achieved cross-sectional remission (Andreasen 32%, CGI-S 41%), compared with haloperidol patients (Andreasen 25%, CGI-S 30%).

Cross-sectional remission rates with quetiapine or haloperidol were largely comparable, based on either the modified Andreasen (without time element) or the CGI-S criteria.

It is well known that schizophrenia has wide heterogenity of its long-term course and outcome. In 2004 ”The Remission in Schizophrenia Working Group” (Andreasen, Carpenter, Kane et al) developed an operational criteria system for the measurement of remission. In their consensus remission was defined by using an absolute threshold of severity of the diagnostic symptoms of schizophrenia rather than improvement from the baseline. Remission is a low-mild symptom intensity level, where the symptoms do not influence behavior. To measure remission they used a complex psychopathological scale, PANSS.

At the beginning of the 1970s we started a study, in which we investigated 185 patients. They were diagnosed according to Leonhard's classification of functional psychoses schizophrenia and cycloid psychoses (schizoaffective psychoses). We reinvestigated them 30 years later, using numerous psychopathological tests, including PANSS. For measuring the level of functioning, we estimated GAF also. The level of functioning was considered “good” when the GAF was higher than 60%. According to that 49% of schizophrenic patients had good prognosis, while this rate of schizoaffective patients was 95%.

We applied the remission conception to our patients and found that only 19% of the schizophrenic patients were in remission, in contrast with schizoaffective patients, where this rate was 90%.

This result confirmed that function and social adaptation did not move in parallel with the severity of psychopathological symptoms, and that this remission concept is a stringent standard.

We studied all the pacients with diagnosis of schizophrenia (DSM IV) who have been admitted in The Psychiatry Clinic II Tg.Mureş, between 01.05.2005-31.12.2005. We analysed the demographic criteria – especially the age and sex repartition, and also the clinical criteria – onset off illness, the corelation with an acute episode, the presence and type of the ideas, of concerns and of autolytic tentatives and also other depressive or psychotic symptoms.

12 (14.1%) from 85 patients with schizophrenia had autolytic ideas, 8 (9.41%) had autolytic concerns and 6 (7.05%) had autolytic tentatives. To exemplify I propose three cases.

The patients with schizophrenia have an important autolytic risk, the tentatives are caused by an added depression or by imperative hallucinations and/or by delusions or by substances abuse.

To evaluate treatment patterns and actual clinical care of schizophrenic patients in Greece.

The Greek ‘ACE’ study is a descriptive, cross-sectional, multicenter national survey conducted in the outpatient setting by 101 psychiatrists (under 3 Coordinators Psychiatrists) proportionately distributed all over Greece who registered during one visit the first twenty consecutive patients presenting at their consultation. Observational period :29/09/2005 -22/12/2005.

Recruited 2040 patients over 18 years, with an ICD-10 primary diagnosis of schizophrenia.

1198 patients were males (58,73%) and 842 females (41.27%). Mean age :40.3 years.

Patient age at the time of disease diagnosis was statistically different between men (26.6) and women(28.8) (p-value<0.0001).

66% of the patients are unemployed, (52.38% due to the disease), 28.24% working and 5.41% students.

Overall, 8.21% had not received any education, 22.67%, had primary education, 8.86%,occupational training, 44.79%,secondary education and 15.47% tertiary education 30.3% of the female patients were married vs 16.6% of the male ones.

82.68% of the patients is not living alone.

In 47.94% of the patients participating, diagnosis schizophrenia had been made more than 10 years prior (escalation of percentages exposed).

Currently 5.88% of the patients were in Acute status(first attack/diagnosis),9.41% in relapse,22.16% presented active symptoms and 62.35% in chronic stable phase.

Family history of schizophrenia existed in 70.72% for males and 69.45% for females. Distribution of the family members affected by the disease exposed analytically.

These results are consistent with equivalent studies carried out in Spain, France and Belgium.

To assess the current treatment patterns and clinical care of schizophrenic patients in Greece.

The Greek ‘ACE’ study is a descriptive, cross-sectional, multicenter national survey conducted in outpatient setting by 101 psychiatrists (under 3 Coordinators Psychiatrists) proportionately distributed all over Greece who registered during one only visit the first twenty consecutive patients presenting at their consultation. Observational period :29/09/2005 -22/12/2005.

Recruited 2040 patients over 18 years, with an ICD-10 primary diagnosis of schizophrenia.

(87.23%) of male patients receive antipsychotic drugs and other therapeutic treatments for schizophrenia in a statistically significantly higher percentage than the one of females (81.47%),(p-value=0.0004).

98.85% of males receive antipsychotic treatments versus 99.56% of females (p-value=0.1185).

35.22% of male patients receive non-drug treatment versus 33.24% of females (p-value=0.3966).

Most often prescribed antipsychotics in this sample are: Risperidone: 28.90%(Males 29.43%, females 28.11%), Haloperidole: 22.96%(23.62%,21.96% respectively,), Olanzapine: 21.39%(20.72%, 22.40%), Aripiprazole: 17.60% (15.68%,20.50%) Quetiapine: 9.50%:(9.00%, 10.25%), Amisulpride: 8.51%(9.78%, 6.59%), Ziprasidone: 8.33% (9.00%,7.32%), Clozapin:7.28% (8.52%, 5.42%), Zuclopenthixol: 1.98% (2.52%,1.17%).

The average daily dosage for each of the above-mentioned medications for the whole sample and by gender has also been assessed whether they are used as monotherapy or as part of polytherapy.

In Greece, more male Schizophrenic patients compared to females are receiving care for their illness. Second generation antipsychotic treatments represent the treatment of choice.

To evaluate the current medical status, clinical care and treatment patterns of schizophrenic patients in Greece.

The Greek ‘ACE’ study is a descriptive, cross-sectional, multicentre national survey conducted in outpatient setting by 101 psychiatrists (under 3 Coordinators Psychiatrists) proportionately distributed all over Greece who registered during one visit the first twenty consecutive patients presenting at their consultation. Observational period :29/09/2005 -22/12/2005.

Recruited 2040 patients over 18 years old, with an ICD-10 primary diagnosis of schizophrenia.

A total of 1716 patients (1033 males and 683 females) were treated with antipsychotics agents. Among them, 52.10% experienced adverse events at the time of data collection

The most frequently reported adverse events is weight gain(45.86%), extrapyramidal symptoms (32.88%), sedation and impaired concentration (24.50%), dry mouth (22.26%), sexual(18.23%) and menstrual (9.50%) problems. Distribution of various adverse events separately for males and females by each medication when received as monotherapy, is also presented.

The percentage of males presenting with high cholesterol values (13.44%) is statistically significantly higher than of females (9.46%) (p-value=0.0124), while this does not happen neither with high triglycerides values (9.21%-males vs 6.99%-females) (p-value=0.1011),nor

with high glucose values (6.72%-males vs 6.71%-females) (p-value=0.9920).

Distribution of high levels of cholesterol triglycerides and glucose, separately for males and females by each medication when received as monotherapy, is also presented.

Weight gain is the most frequently reported adverse event in this study. It is important to patients to receive the most appropriate treatment, taking in consideration both symptom control as well as potential side-effects.

Evidence shows that the hospital-based character of psychiatric services has a negative impact on the personal and social life of the psychotic patients. This situation is worse in rural areas where the Psychiatric Care facilities are fewer. In a 5-year study we investigate the therapeutic role of the Ambulatory Mobile Care Unit in the provinces of Fokida and Evros.

45 patients, aged between 17-67, diagnosed with psychosis (schizophrenia, schizoaffective disorder, delusional states, bipolar disorder etc.) were studied. Most of them were unemployed (56%), living with their parents, and belonged to the lower or middle class. An experienced psychiatrist-supervisor, other psychiatrists, trainees, psychologists, social workers and nurses were part of the intervention team that helped the patients in different stages of the disease (acute state, stable condition).

The intervention of the Mobile Care Ambulatory Unit resulted in:

1. a) Increase in the Employment Rate of the Patients (more than half of the patients has been employed in the end of the intervention)

2. b) Improvement in social abilities (more than 4/5 of the patients had improved relations with the local community c) Leisure time activities: acquisition of new hobbies in more than 2/3 of the patients d) Insight: most of the patients came in terms with their disease e) Nevertheless, very few of them managed to form their own family.

The mobile unit intervention has had a significant effect in most aspects of the life of the psychotic patients.

The limited number of extramural residential facilities in the rural areas of Greece leads in the diminished effectiveness of the follow-up of the psychotic patients and the relapses of their condition. The goal of our study was to investigate the factors involved in the number and duration of the relapses, as well as the role of the intervention of the Ambulatory Mobile Units in modifying these parameters.

By using different statistical techniques 45 patients, aged between 17-67, were studied. In a 5-year follow-up, parameters like the number of relapses and their duration were correlated with socio-demographic variables and parameters concerning the personal and family background of the patient. A standard team consisting of an experienced psychiatrist-supervisor, other psychiatrists, trainees, psychologists, social workers and nurses were collaborating with the patients.

The number of relapses was correlated with:

1. a) The social abilities of the patients

2. b) The ability to cope up with their disease

3. c) Their age

4. d) The duration of their previous hospitalizations

5. e) The compliance with the suggested therapy

6. f) The presence of positive psychiatric anamnesis in the patient's family

7. g) The employment status

The duration of the relapses was correlated with:

1. a) The social achievements of the patient

2. b) Their employment status

3. c) Their leisure time activities

4. d) The frequency of their follow-ups

5. e) The presence of positive psychiatric family background

The Ambulatory Mobile Unit plays an essential role in the number and duration of the relapses.

Non-compliance increases risk of relapse, hospitalizations, and suicide attempts, which worsens patient's outcome. Adherence must be understood not only in terms of medication compliance but also adherence to Mental Health Therapeutic Programmes. The aim of this project is to evaluate adherence of patients with Schizophrenia to programmed appointments with psychiatrist and the influence of several factors.

Descriptive 5-year study based on attendance to consultation programmed by a physician within a rural Community Mental Health center, Sub-analysis of compliance rate will be performed based on: gender, age, Schizophrenia subtype, disease evolution, time of evolution, either oral or long-acting neuroleptic medication, family characteristics, participation in Home Visit Programme (HVP). Within records obtained from Andalucia Mental Health Information System (S.I.S.M.A.), number of programmed consultations during last 5 years, non-attended consultations, evidence of medication abandon and previously mentioned factors, will be assessed.

Characteristics of abandoning group.

1. - % non-attended visits is higher (18% vs. 11,5% of non-abandoning group).

2. - % patients under only oral treatment is higher (58% vs. 35,5% of non-abandoning group) and % under parenteral treatment is lower (42% vs. 64,5%).

3. - % Home Visits is lower (10,5% vs. 24% of non-abandoning group).

4. - Schizoaffective patients are more likely to abandon (44%) followed by residual schizophrenic patients (35%).

Actions to avoid patient's abandons include:

1. - Close follow-up of patients who start missing programmed appointments especially of schizoaffective and residual schizophrenic

2. - Parenteral treatment prescription.

3. - Enrolment to HVP.

The diagnosis of hyperprolactinaemia is made when raised serum prolactin levels are found on two separate occasions. Antipsychotics affect the hypothalamic dopamine system or pituitary dopamine receptors and can result in an elevated prolactin level. The aim of the study was to evaluate the prevalence of hyperprolactinaemia in patients with schizophrenia treated with either risperidone or olanzapine.

Sixty patients with schizophrenia (DSM IV criteria) participated in this study. Their mean age was 31.1 ± 8.6 years. They remained on regimens of risperidone (n=26) or olanzapine (n=34) monotherapy. Mean duration of treatment in risperidone group (RIS) was 24.7 ± 19.2 months, in the olanzapine group (OLA) was 17.0 ± 11.3 months.

Blood samples for analysis were fasting morning samples to evaluate prolactin (two measurements).

In 92.3% treated with risperidone hyperprolactinaemia was detected and in 76.5% patients treated with olanzapine.

There was no positive correlation beetween a presence of hyperprolactinemia and age of patients treated with risperidone. Strong negative correlation was detected beetween hyperprolactinemia and age of patients treated with olanzapine. (r=-0.47) (p<0.01) hyperprolactinemia was more prevalent in younger patients.

There was strong negative correlation beetween prolactin levels and lengh of treatment in a group of patients treated with risperidone (r=-0.42) (p<0.05). Prolactin level was decreasing with longer treatment.

1. 1. Hyperprolactinaemia occurs with nearly same prevalence in patients treated with risperidone and olanzapine.

2. 2. Hyperprolactinemia affects more younger people trated with olanzapine.

3. 3. Level of prolactin decreases with longer treatment with risperidone, but not with olanzapine.

This study aimed to examine the relationships between subjective attitudes towards antipsychotics and objective cognitive function in schizophrenia patients.

The subjects of study were clinically stable schizophrenic patients (N=55) who were hospitalized in Naju National Hospital. They were grouped into positive (N=35) and negative drug attitude groups (N=20) by Drug Attitude Inventory (DAI-10). They were assessed using Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, Extrapyramial Symptom Rating Scale, UKU side effect rating scale, Social and Occupational Functioning Assessment Scale and Subjective Well-being Under Neuroleptic Treatment. A battery of neurocognitive tests were also administered using Seoul Computerized Neurocognitive Function Test.

Patients between positive and negative drug attitudes did not differ in social demographic and clinical characteristics. They also showed no differences in neurocognition tests except a subset of verbal auditory learning test.

These findings may indicate no associations between subjective drug attitudes and objective neurocognitive dysfunctions in schizophrenic inpatients. It suggests that subjective aspects measured by DAI may be a distinct dimension from objective neurocognitive profiles in terms of compliance.

1) To examine the nature and extent of cognitive impairment in first-episode early-onset psychosis (EOP) and 2) To search for differential cognitive impairment profiles among the diagnosis subgroups.

This study describes the basal neuropsychological results of the child and adolescent first-episode psychosis study (CAFEPS), a spanish multicenter longitudinal study. One hundred first-episode patients with EOP and 98 healthy controls underwent a comprehensive neuropsychological assessment. Three diagnostic categories were established: schizophrenia spectrum disorders (n=45), affective psychosis (n=28), and psychosis not otherwise specified (n=28). Baseline diagnoses were confirmed at a 6-month follow-up visit.

Performance of patients was between 0.88 and 2 standard deviations below that of controls in all cognitive domains: attention (p<0.001), working memory (p<0.001), executive functioning (p<0.001), and memory (p<0.001). The three diagnostic subgroups did not differ from one another in terms of impaired/preserved cognitive functions and degree of impairment.

The pattern and degree of cognitive impairment in first-episode EOP patients is similar to that reported in first-episode adult-onset patients. Our results failed to identify significant differences among diagnostic subgroups at the onset of the illness. The longitudinal design of the present study will allow for identification of potential differences in the course of cognitive impairment.

Recent years have seen a particular attention towards the research of particularities of cognitive processes in schizophrenia.

This study aims to investigate neuropsychological impairment in schizophrenia patients and their siblings.

Cognitive functioning in 30 schizophrenia patients, 30 unaffected siblings and 30 unrelated healthy controls was assessed using verbal fluency tests (letters and categories) and several computerized memory and executive function tests.

The patients performed significantly poorer than controls on all cognitive tests. Unaffected siblings demonstrated better performance than patients on some measures of spatial memory and executive function, but the performance was worse then controls. Patients and siblings demonstrated impaired verbal fluency performance.

Patients with schizophrenia and theirs unaffected siblings shared a deficit in verbal fluency.

To evaluate trends in the use of antipsychotic drugs in Lithuania between 2003 and 2005 years.

The data on total sales of antipsychotic drugs in Lithuania over three years (2003-2005) were obtained from IMS Health Inc. Drugs were classified according to the Anatomic Therapeutic Chemical system, use was quantified in terms of defined daily doses. Data were calculated by DDD methodology, expressed in DDDs per 1.000 inhabitants/day. The pharmacoeconomic analysis was performed by cost minimization and reference price methodology.

The total antipsychotics consumption increased by 16% over three years period reaching the value of 5,5 DDD/1000 inhabitants/day. Use of conventional antipsychotics has increased by 3%, atypical antipsychotics by 34%. The expenditures of antipsychotics has reached 39 mln Litas (in 2005), of which 48% was costs for atypical antipsychotic agents. Setting the reference price of risperidone (according to the meta-analysis results of effectiveness) for atypical antipsychotics it would be possible to rationalize schizophrenia treatment using 10,68 mln Litas extra money (1€ = 3,4528 Lt).

The use of total antipsychotic drugs continues to increase because of the increased use of atypical antipsychotics and some conventional antipsychotics. According to the meta-analysis results risperidone is the most effective drug for schizophrenia treatment. Considering the similar efficacy of other atypical antipsychotics and the increased high expenditures of atypical antipsychotics it is extremely important to consider the cost-effectiveness of antipsychotics. Performed cost-minimization analysis using the reference-based pricing estimated the possible reduction of total antipsychotics expenditures by 28%, the possible schizophrenia treatment rationalization.

To evaluate attitude and adhesion of psychiatric patients towards its treatment, specially psychotic patients with neuroleptic treatment

This is an open study on a population of 36 hospitalised patients in Acute Psychiatric Unit at Hospitality Center Benito Menni of Valladolid (Spain). Basic social-demographic information, characteristics of disease and treatment of each patient, their answers to an own questionnaire of quality assistance and scores derived from the application of Drug Attitude Inventory (DAI) has been collected in a protocolized form. These scores has been analysed with SSPS statistical program, crossing variables such as diagnosis or treatment.

Some results are detailed as follows:

Male 38,9%, female 61,1%. Mean age 52,89.Usually single 50% that live alone 54,6% in urban habitat 65,6%, majority with schizophrenia 27,8%, followed by depressive spectrum 22,2%., with a combination of anxiolytics (lormetazepam + lorazepam) 33,3%, and risperidone (22,2%) or olanzapine (27,8%) in most cases.

After analysis we found statistical significance in differences by gender – better in case of women -, diagnosis – better attitudes with higher scores in patients with non psychotic disorder - and atypical neuroleptic treatment.

1. 1. Adherence and better attitudes were more likely in female patients, also schizophrenic, probably due to their caregivers role in society.

2. 2. As expected, non psychotic patients with higher conscious of illness are more likely to see treatment as useful.

3. 3. Atypical neuroleptics seems to be better in order to achieve proper treatment adherence

To address and better understand the problem of high suicide rates in widows and widowers.

Sex and age specific suicide data collated by marital group were extracted from Swiss mortality statistics for the period 1991-2003. The mortality in the first week / month / year of widowhood was calculated based on person-year calculations.

Cross-sectional analysis by sex and age-group confirms the existence of different suicide rate patterns according to marital status. Moreover, the profiles of suicide methods differ. In particular, suicide methods which may be associated with impulsive suicides, such as firearms or poisoning, are relatively frequent in the widowed. The suicide risk of widowed persons is extremely high in the days and weeks immediately after bereavement.

Suicide risk and suicide behavior varies systematically according to marital status. In particular, widows and widowers emerge as a group suitable for preventive methods because of the existence of a time window when there is increased risk. Moreover, widowed persons are a clear-cut risk group under the aegis of undertakers, priests and perhaps general practitioners.

Control of gene expression is essential for the establishment and maintenance of all cell types, and is involved in pathogenesis of several diseases. Accurate computational predictions of transcription factor regulation may thus help in understanding complex diseases, including mental disorders in which dysregulation of neural gene expression is thought to play a key role. However, predictions via bioinformatics tools are typically poorly specific.

We have developed and tested a computational workflow to computationally predict Transcription Factor Binding Sites on proximal promoters of vertebrate genes. The computational framework was applied to groups of genes found to respond to antipsychotic drugs. Our approach for the prediction of regulatory elements is based on a search for known regulatory motifs retrieved from TRANSFAC, on DNA sequences of genes' promoters. Predictions are thus weighted by conservation. These predictions are further refined using a logistic regression to integrate data from co-regulated genes.

Consistent results were obtained on a large simulated dataset consisting of 5460 simulated promoter sequences, and on a set of 377 vertebrate gene promoters for which binding sites are known (TRANSFAC gene set).

Our results show that integrating information from multiple data sources, such as genomic sequence of genes' promoters, conservation over multiple species, and gene expression data, can improve the accuracy of computational predictions. The results of predictions on genes involved in antipsychotics response include the drug target Homer 1, involved in glutamate synaptic plasticity response.