Clozapine is the established antipsychotic for patients refractive to, or intolerant to, other antipsychotics. Despite its unfavorable safety profile requiring continued clinical and haematological monitoring, clozapine is tolerated relatively well due to the low risk of associated extrapyramidal effects. Our objective was to assess the safety and efficacy associated with the initiation and continued monitoring of clozapine therapy for the treatment of psychotic disorders in the community.

A retrospective single-centre study of patients on clozapine therapy (n=45) for the treatment of psychotic disorders managed within the community between 01/07/05 and 30/06/06. Parameters evaluated included pre-therapy clinical/laboratory evaluation, pre-clozapine antipsychotic medication history, clozapine treatment dosage and duration, initial/late adverse effects, reasons for treatment cessation and psychiatric readmission rate.

The mean age of our patient cohort was 42.2 years. There was a male predominance with a male:female ratio of 2.5:1. Patients were treated with an average of 3.5 different antipsychotic regimens prior to clozapine commencement. 97.8% of patients commenced clozapine due to treatment resistance. The most common early side-effect was sinus tachycardia (24.4%) followed by hypersalivation (15.6%), whilst weight gain (8.9%) was the most common late onset side-effect. There was 2.2% psychiatric admission rate on clozapine therapy and was due to treatment non-compliance.

Clozapine is a very effective atypical antipsychotic for managing patients refractive to, or intolerant to, other antipsychotics. Despite its impressive clinical efficacy, clozapine has a significant side-effect profile warranting continued patient vigilance and greater research on its short- and long-term safety.

Only a few randomized clinical trials have tested the effect on transition rates of intervention programs for patients with sub-threshold psychosis-like symptoms.

To examine whether integrated treatment reduced transition to psychosis for first-contact patients diagnosed with schizotypal disorder.

Seventy-nine patients were randomized to integrated treatment or standard treatment. Survival analysis with multivariate Cox-regression was used to identify factors determinant for transition to psychotic disorder.

In the multivariate model, male gender increased risk for transition to psychotic disorder (relative risk = 4.47, (confidence interval 1.30-15.33)), while integrated treatment reduced the risk (relative risk = 0.36 (confidence interval 0.16-0.85)). At two-year follow-up, the proportion diagnosed with a psychotic disorder was 25.0 percent for patients randomized to integrated treatment compared to 48.3 percent for patients randomized to standard treatment.

Integrated treatment postponed or inhibited onset of psychosis in significantly more cases than standard treatment.

There are many studies reporting poor insight in schizophrenic patients. Other studies demonstrated deficits in executive functions in these same patients.

The results of empirical studies that try to establish the relationship between levels of insight and various clinical and neuropsychological variables are not consistent.

The aim of this study was to establish the relationship between the executive functions, as defined by the Behavioral Assessment of Dysexecutive Syndrome (BADS- N. Alderman, 1996) and the level of insight, evaluated by Assessment of Insight in Psychosis scale (I. Marková, 2002). We also tried to correlate some clinical variables (age, gender, age of onset, schoolarity, type of pharmacotherapy, severity of psychopathology) with the level of insight and executive dysfunction.

we studied 50 schizophrenic outpatients of the Psychiatry Department of our Hospital, whose age ranged between 16 and 60 years, and who had stabilized disease. Informed Consent was obtained from all participants.

We evaluated patients trough the following sequence: clinical interview in order to obtain clinical and social variables; Mini Mental State Examination (MMSE – M. Folstein,1975); Positive and Negative Syndrome Scale (PANSS - Kay SR, 1987),Assessment of Insight in Psychosis Scale (I. Marková, 2002) and Behavioral Assessment of Dysexecutive Syndrome (BADS- N. Alderman, 1996).

The study is now under statistically evaluation.

To compare CATIE, a randomized double blind study, and SOHO, a 3-year prospective non-randomized observational European study of outpatients with schizophrenia, on the Number Needed to Treat (NNT) for all-cause medication discontinuation. NNTs place data into a clinically meaningful context - the number of patients needed to be treated with one antipsychotic instead of another to prevent one negative outcome, defined here as one additional medication discontinuation for any cause.

Rate of medication discontinuation for any cause during the 18 months post initiation was calculated for patients newly initiated on olanzapine (N=4247), risperidone (N=1549), quetiapine (N=583), amisulpride (N=256), clozapine (N=274), oral typicals (N=471) or depot typicals (N=348). Cox models were employed to adjust for treatment group differences at baseline. NNTs with their 95% confidence intervals were calculated and compared with published NNTs for CATIE (Phase 1).

The NNTs for all-cause discontinuation of olanzapine vs. each studied atypical antipsychotic during the 18 month following medication initiation in SOHO were comparable to CATIE: 4.3(95% CI: 3.6–5.3) for olanzapine vs. quetiapine (5.5 in CATIE); 16.1(11.0–28.1) for olanzapine vs. risperidone (10.1 in CATIE); 6.9(5.2–10.1) for olanzapine vs. oral typicals (9.0 in CATIE for olanzapine vs. perphenazine).

The NNTs for all-cause medication discontinuation based on CATIE appeared comparable to NNTs based on SOHO. The NNTs for olanzapine therapy were consistently better when compared to each studied atypical antipsychotic (except clozapine) and when compared to typical antipsychotics. Results should be interpreted conservatively, due to the observational design of SOHO.

The primary objective of this FDA-requested study was to examine the tolerability, safety, and pharmacokinetics (PK) of 20, 25, and 30 mg/day of aripiprazole in children and adolescents, ages 10-17.

21 patients were enrolled in this open-label, sequential cohort trial that employed a forced escalation paradigm. A 2 mg starting dose was increased to 5, 10, 15, 20, 25, or 30 mg (depending on the final dose) in 2-day, stepwise intervals. After this initial dose-escalation phase, subjects were maintained at their target dose for an additional 14 days. Study medication was given once daily. Preferential enrollment was given to patients with schizophrenia or bipolar illness. Blood samples were collected for aripiprazole concentrations.

Using the described dose-escalation schedule, all 3 dose levels were well tolerated, in general. One subject discontinued treatment due to acute, moderate dystonia. Other adverse events were in the mild/moderate range and were transient in nature. Aripiprazole pharmacokinetics are linear across doses and similar to that observed in adult patients.

Conclusions:

• • Doses of 20, 25 and 30 mg/day (following titration from a starting dose of 2 mg) are generally well tolerated in children and adolescents without regard to gender or psychiatric diagnosis.

• • Aripiprazole pharmacokinetics are linear in child and adolescent patients.

The caudate nucleus is involved in cognitive function. Schizophrenic patients showed cognitive dysfunction. It has been reported that volume reduction of the caudate nucleus was associated with cognitive impairment in schizophrenic patients. Because treatment with olanzapine improves cognitive dysfunction in schizophrenia, olanzapine may affect the caudate nucleus volume in patients with schizophrenia. We measured volumes of grey and white matter in the caudate nucleus of schizophrenic patients.

Ten schizophrenic patients and ten healthy subjects were examined magnetic resonance imaging. Ten patients were scanned at the time of pre-treatment and post-treatment with olanzapine. MR data analysis was performed using BRAINS software in order to measure grey and white matter volume of the caudate nucleus.

Schizophrenic patients had reduced volume of grey and white matter of the caudate nucleus compared with healthy subjects. The average duration of treatment with olanzapine was 186 days in schizophrenic patients. The volume of grey and white matter in the caudate nucleus at the time of post-treatment was significant larger than that at the time of pre-treatment with olanzapine in patients with schizophrenia. There was no significant difference between the volume of grey matter of the caudate nucleus at the post-treatment with olanzapine and that of healthy subjects.

Schizophrenic patients had reduced volume of the caudate nucleus. Treatment with olanzapine may improve volume reduction of grey matter of the caudate nucleus in schizophrenic patients.

In the last year, a new antipsychotic (AP) was approved in Spain for treatment of schizophrenia: ariprazole. Objetives: 23 clinical psychiatrists of Acute Units throughout Spain have constituted a regular work group (PSIQ-A) for the purpose of sharing clinical experiences and examining topics of interest to our daily clinical practice.

In periodic meetings, members of PSIQ-A have made a compilation of different approaches to distinct clinical situations that hospitalized schizophrenic patients may present: approach in Emergency Room to try to reach a consensus, specifically with respect to ariprazole use in each situations.

Usually recommended dosage with predominance of positive symptoms: 25-30 mg/day (generally more than 15 mg/day) and with predominance of negative symptoms: smaller doses are sufficient and effective. Because of the demands of Acute Care rapid changes are chosen (about 1 week), except with clozapine and depot preparations (2 weeks) with full doses of ariprazole in 1-3 days and tapering off of previous AP. The initial, temporary association of drugs with a more sedative profile is frequent (BZD, levomepromazine, quetiapine). Some benefits have been: Reduction of psychotic anxiety; possibility of improving insight; excellent tolerance, even at high doses; response in negative-residual patients: more activity, more eagerness to do things, “evident improvement in the most chronic patients”.

Ariprazole is a new and interesting drug in the approach to the phase of decompensation and admission of patients with schizophrenia, with good tolerability in major areas of patient concern and feeling well-being and improving insight.

The importance of early recognition and treatment of the first psychotic episode is well documented in literature. This study aims to describe and analyze the sociodemographic and clinical characteristics of a sample of patients admitted in a psychiatric ward for their first psychotic episode.

Data from 48 patients was retrospectively analyzed using a specific clinical protocol. Inclusion criteria were admission with a first psychotic episode during January 2003 to June 2005. Patients with primary affective and organic disorder were excluded. ACESS was used for statistic analysis.

Patients were aged 19-56, mainly of the masculine gender (77%), single (68%), living with own family (89%), and receiving any kind of social support (13%).

Main diagnoses were Schizophrenia (54%); Persistent Delusional Disorders (17%); Acute and Transitory Psychotic Disorders (29%).

Age of onset was 28 years (median) for males and 36 years for females. Onset was

insidious for 44% of the patients and the Time Disease Untreated (TDU) mean-2,2 month; median 18,8 month, witch is similar with literature data. Ten percent were involuntarily admitted and 84% were taking oral atypical antipsychotic with total compliance for 33% and partial for 25% of patients.

Only 23% of the patients or their families were attending therapeutic groups.

The results of our study in part agree with the data from the literature on the other hand they reflect the characteristics of our healthcare system and population, and can provide ways to improve care.

At present,the need of antipsychotic treatments for the improvement of the condition of people with psychotic disorders is unquestionable.Despite the current availability of highly effective drugs with few secondary effects,the main cause behind hospitalization is still the lack of compliance.

Analysis of the determining variables behind the need for hospitalization and the influence of the types of antipsychotic treatments.

Retrospective and follow-up analysis of psychotic patients hospitalized in the Psychiatric Ward of the Hospital de Conxo (1998-2005).Three groups of patients:with Oral neuroleptics(170), with Depot typical neuroleptics (238),with Long-Acting Risperidone(60);and comparison based on treatment maintenance.

Males,day-to-day living with the family of origin and single status are predominant in all three groups,although in a higher proportion in the Long-Acting Risperidone one(75,71 and 85%respectively).Only 7% of the patients with Long-Acting Risperidone completed their university studies,62% were pensioners.The average duration of hospitalization periods is 21 days for the patients with Long-Acting Risperidone,23.3 days in the Oral group,29.5 days in the Depot group.The main cause behind re-hospitalization is the lack of compliance(68% in Depot group),whilst after the introduction of Long-Acting Risperidone,no compliance rate is 59%.If we compare the number of hospitalizations/year of the patients with Long-Acting Risperidone,before and after its introduction,the rate is reduced significantly from 0.89 to 0.73.

Despite the fact that patients treated with Long-Acting Risperidone show a more seriously ill condition and less social capacity,they have less need for hospitalization than patients treated with Depot neuroleptics.Median lengths of stay were shorter than patients in the other two groups,and are less re-hospitalized after the introduction of this treatment.

SOS compared during 2 years medical costs in Belgian out-patients with schizophrenia.

Patients older than 18 and stabilized with haloperidol(H), olanzapine(O) or risperidone(R) monotherapy entered this observational study at discharge from the hospital.

Of 323 patients included, 68% (219/323) completed the study (H59% (19/32), O66% (99/149), R71% (101/142)). In the R group were more first episode patients (H6%, O17%, R27%). H patients were more chronic with more previous hospitalizations.

Treatment continuation (no drop out, without medication change or addition) was 31%(H), 50%(O) and 43%(R). The mean dosages were H 8.9 (±9.6), O 14 (±6) and R 4.2 (±1.9) mg/day. Two years medical costs were H 30484 (± 36332), O 20897 (± 27863), R 20916 (± 31776) (NS)

The CGI improved during the first 3 months and then remained stable. The percentage of patients with at least 1 EPS at the last visit was: H66%, O35% and R39% (p=0.005) and at least 1 sexual/reproductive problem was H69%, O40%, R44% (p=0.013). Weight gain was H 0.53 ± 5.0, O 3.3 ± 8.3 and R 3.2 ± 8.4 kg.

Even in this group of stabilized patients, treatment continuation was poor: in only 1 out of 3 haloperidol patients, treatment was not changed during the 2 years follow up. The fewest treatment change was in the olanzapine group (1 out of 2). Treatment cost was not significantly higher in the haloperidol group and similar in olanzapine and risperidone group as hospitalization was the main cost driver.

A randomised study (D1444C00004) to show superior relapse prevention with quetiapine sustained release (SR) versus placebo.

327 patients with schizophrenia were switched to open-label, once-daily quetiapine SR dosed at 300 mg on Day 1, 600 mg on Day 2, then 400-800 mg for a 16-week stabilisation period. Stable patients (clinically and by dose) were randomised (n=197; double-blind phase) to either quetiapine SR (400-800 mg/day) or placebo. Primary endpoint: time from randomisation to psychiatric relapse (hospitalisation for worsening schizophrenia, PANSS increase ≥30%, CGI-I score ≥6, or need for additional antipsychotics). An independent Data Safety Monitoring Board (DSMB) monitored the study. Planned analyses: interim, after 45 and 60 relapses (to permit termination if a significant treatment difference in primary endpoint was observed); final, after 90 relapses.

Early termination occurred after the first interim analysis (following DSMB recommendation) as quetiapine SR (mean dose 669 mg/day; mean randomised-treatment period 4 months) was significantly superior to placebo for time to relapse: HR 0.16 (95% CI 0.08, 0.34; p<0.001). Numbers (%) of relapses were: 9 (10.7%), quetiapine SR; 36 (41.4%), placebo (interim ITT population). Estimated relapse rate at 6 months was: 14.3%, quetiapine SR; 68.2%, placebo (difference 54% [95% CI 42.5, 65.4; p<0.001]). Incidence of: treatment-related AEs 18% (quetiapine SR), 21% (placebo); total EPS-related AEs 1.1% and 1%, respectively. One patient in each group withdrew due to AEs.

Once-daily quetiapine SR (400-800 mg/day) was effective versus placebo in preventing relapse in patients with clinically-stable schizophrenia and was well tolerated during longer-term use.

Patients with schizophrenia exhibit various cognitive dysfunctions, most of them rendered evident by language.

The aims of the current study are: to compare the global semantic performance of schizophrenics with those of normal controls and to explore the schizophrenics' semantic network.

62 schizophrenic patients, admitted to the Second Psychiatric Clinic Cluj, diagnosed according to ICD-10 criteria and 158 healthy controls were evaluated with tasks for semantic fluency (animals, fruits and body parts).

The correlation between clinical symptoms, demographic data and the verbal fluency variables has been determined using Pearson's correlations. The data were analysed using ANOVA and for semantic fluency this was followed by multidimensional scaling (MDS).

Patients with schizophrenia generated fewer words than healthy controls on semantic fluency tasks. The MDS analysis showed that the semantic structure for schizophrenics with hallucinations was more disorganized than that for the schizophrenics without hallucinations. The schizophrenics with hallucinations appeared to lack any organisation or logical associations within their semantic network of animals, fruits or body parts.

The comparison between schizophrenia patients as a whole and normal controls indicated impaired semantic structure in the patient group, in addition to decreased word production.

To assess subtle pre-psychotic anomalies of subjective experiences in adolescents might become a key point for early screening of psychotic risk. Yet the ideal instrument would need to be a brief, responsive, reliable, and valid measures that can be implemented in strategic extra-clinical community settings with minimal cost and burden. The Frankfurt-Pamplona Subjective Experience Scale is a 18-item, likert-format, self-report measure developed on the basis of empirically-derived condensation of the Frankfurt Complaint Questionnaire (Cuesta et al., 1996).

The objective of this study was to field test the Italian adaptation of the FPSES, assess its reliability and validity and explore eventual overlap with schizotypal personality traits.

A pilot field test was implemented in a randomized sample of both high school and university classes in the urban area of Novara (Italy). A total of about 208 students agreed to participate. Internal consistency and factor analytic methods were used to assess the psychometric properties of the instrument.

The FPSES revealed a high internal consistency and a monofactorial item segregation independent of schizotypal dimensions.

Analyses of the FPSES supported its reliability and validity for assessing experiential vulnerability in a non-intrusive way. Self-perceived experiential vulnerability showed only minimal overlap with concomitant schizotypal traits and defines a putatively autonomous domain of individual pre-psychotic liability. Normative data for the sample are presented.

albeit ultra-high risk (UHR) mental state for developing a psychosis is currently defined mainly by attenuated (APS) and transient psychotic symptoms (BLIPS), subtle not-yet psychotic anomalies of self-experience occur in a substantial proportion of prodromal patient even prior to any detectable diagnostic symptom.

in-depth, multiple, phenomenologically-driven psychiatric interviews were conducted in a sample of about 14 first admitted prodromal patients and their families, together with standardized psychometric evaluation.

Subjects' detailed first-person self-descriptions were collected and transcribed in the clinical files and re-evaluated, specifically targeting the biographical emergence of disorders of self-experience, interpersonal attunement and axiological idiosyncrasy.

recurrent patterns of morbid self-experience were identified, especially inhering a fading of the basic sense of self-intimacy (i.e. diminished ipseity or self-affection) and a related strive to maintain the coherent self-narrative. Such patterns were meaningfully connected with the current clinical symptomatology and interpersonal functioning of the patients. Phenomenological-oriented interviewing revealed dramatic effects in modulating contingent subjective self-stigmatization and environmental expressed emotion.

not-yet psychotic anomalies of subjective experience are relevant in the characterization of UHR mental states and are subtended by profound transformation of the basic structures of consciousness (i.e. intentionality, temporality, spatiality, embodiment). Such prereflective and near-ineffable experiences can be grasped by means of a phenomenological approach.

This study assessed the prevalence of MS in patients treated with antipsychotics using two proposed NCEP-ATP-III definitions.

A retrospective, cross-sectional, multicenter study was carried out by 117 Spanish Psychiatrists (The CLAMORS Collaborative Group). Consecutive outpatients meeting DSM-IV criteria for Schizophrenia, Schizophreniform or Schizoaffective Disorder, under antipsychotic treatment for at least 12 weeks, were recruited. MS was defined as fulfilment of at least 3 of the following components: waist circumference >102(men) / >88(women)cm (NCEP-ATP-III definition), or BMI>=28.8 kg/m2, (revised NCEP-ATP-III definition); tryglicerides>=150mg/dL; HDL-cholesterol <40mg/dL(men) / <50mg/dL(women); blood pressure >=130/85; fasting glucose >=110mg/dL. Kappa coefficients and bivariate logistic regression models were applied.

1452 evaluable patients (863 men, 60.9%), 40.7+12.2 years (mean+SD) were included. MS was presented in 24.6% [23.6%(men), 27.2%(women); p=0.130)] (NCEP-ATP-III definition), and in 25.5% [25.6%(men), 25.6%(women); p=0.9924)] (revised NCEP-ATP-III definition). Kappa coefficient between both definitions was 0.81 [0.81(men), 0.84(women)]. Obesity component was present in 42.4% of patients [34.3%(men), 54.5%(women); p<0.001] when defined by waist circumference (NCEP-ATP-III definition), and in 38.2% [36.7%(men), 39.4%(women); p=0.3156] when defined by BMI (revised NCEP-ATP III definition). Obesity component was less associated to presence of MS when it was defined by waist circumference (OR=9.99, 95%CI:7.37-13.55), than when it was defined by BMI (OR=11.19, 95%CI:8.42-14.87).

Obesity plays a central role in the NCEP-ATP-III definition of MS. Prevalence of the abdominal obesity component may be assessed by either the measurement of the waist circumference or by calculation of the body mass index without losing reliability.

On behalf of the CLAMORS Collaborative Group.

The conventional approach in measuring treatment persistence tended to use only the first prescription episode even though some patients received multiple prescriptions of the same medication. In this study, we assessed the extent to which patients received multiple prescriptions and levels of treatment persistence associated with each prescription episode.

Using 2000-2004 data from the Veterans Health Administration in the United States, we identified patients with schizophrenia using ICD-9-CM codes and defined initiation of the target agent as 6-month "clean" period of no target drugs prior to initiation and reserved one year following the initiation to calculate treatment persistence, or time to discontinuation, as defined by a gap of >15 or > 30 days.

The study found that about 25% of the patients had two or more treatment episodes, and that the levels of treatment persistence exhibited variation for patients with one, two, or three prescriptions. Generally speaking, among patients with one prescription, initiators of typical agents tended to fare worst in the level of treatment persistence. This finding suggests that conventional approach in calculating treatment persistence tends to underestimate the gap between typical and atypical agents.

Considering that patients with different number of treatment episodes might differ in disease profiles, this treatment episode-specific approach offered a fair comparison of the levels of treatment persistence across patients with different number of treatment episodes.

Akathisia remains a challenge in routine psychiatric practice, despite the widespread use of second generation antipsychotics (SGAs). This analysis was performed to quantify and qualify clinical characteristics of akathisia in schizophrenia or schizoaffective disorder patients experiencing an acute relapse who were randomized to receive aripiprazole, or placebo in 5 pooled short term trials.

A post hoc analysis of the safety dataset was conducted to assess clinical aspects of akathisia in five 4- or 6-week, double-blind, randomized trials comparing aripiprazole (2, 5, 10, 15, 20, 30 mg/day) to placebo.

A total of 1,635 patients was included in this analysis (aripiprazole: n=1170; placebo: n=465). Akathisia was reported by 9% of the aripiprazole-treated patients and 6% of those receiving placebo. Among those reporting akathisia, more patients receiving aripiprazole (83%, n=86) reported this AE within the first 2 weeks of the trials when compared to placebo (69%, n=20). The mean and median duration of akathisia was generally low in both groups (Mean: aripiprazole=12.5 days and placebo=4.2 days; Median, aripiprazole=5.0 days and placebo=1.5 days). The percentage of patients reporting akathisia at endpoint (BARS Item 4≥2) was similar between aripiprazole- (16%) and placebo-treated patients (14%).

In the aripiprazole and placebo groups, akathisia appeared to occur early in treatment, was time-limited, and was associated with high rates of concomitant benzodiazepine usage. Additionally, most cases of akathisia were reported as mild to moderate and rarely associated with treatment discontinuation.

One factor greatly influencing the prognosis and progression of the Schizophrenia is compliance and it is essential to find new drugs which carry minimal side effects.

To identify the profile of patients who are treated with aAripiprazole and to assess the effectiveness, tolerability and treatment adherence.

This was a multicentre, observational, retrospective study with participation of 200 psychiatrists. Data from the medical records of patients treated with aAripiprazole with at least two months were collected between October and December 2005.

A total of 997 patients were included. 95% of patients had been treated with another drug prior to receiving aAripiprazole. The pattern for switching from the previous treatment was substitution in 75% of cases and addition in 25%. Reasons for switching were: 56,6% lack of efficacy and 35,6% adverse reactions. The investigator's assessment of aAripiprazole's effectiveness and tolerability showed these was very good or good in 76% and 90% of cases respectively. Around 87.6% showed good treatment compliance. Efficacy of treatment was correlated with duration of the disease: the proportion of patients with good efficacy is greater in patients who had suffered the disease for less than ten years (78.7 vs. 73.8%) (p=0.01).

aAripiprazole was considered to have a good effectiveness and tolerability in most patients. Effectiveness was greater in the acute phase of the disease, in patients with shorter duration of the disease and in those only taking full dose aAripiprazole