European First Episode Schizophrenia Trial Research Articles

Clinical Validity of Subjective Clinical Prognosis in First Episode Psychosis Schizophrenia Patients: An Analysis of Data from the European First Episode Schizophrenia Trial (EUFEST) Study.

PurposeThis study examined the validity of subjective clinical prognosis (SCP), a commonly used clinical tool, in first episode psychosis patients included in the European First Episode Schizophrenia Trial (EUFEST) study.Patients and MethodsThe study comprised 455 patients from the EUFEST trial (mean age 25.92, SD=5.45; 188 (41.31%) women, 267 (58.69%) men). SCP was classified into three mutually exclusive groups: “good prognosis” (GP) (n=265), “average prognosis” (AP) (n=131), and “poor prognosis” (PP) (n=59). The validity of the SCP was assessed by investigating the differences between the SCP groups and completer or responder status of the patients, during 1 year of the trial.ResultsThe proportion of completers was significantly higher in the GP group (64.4%) compared to the AP group (25.6%) (OR=1.62, 95% CI=1.062–2.476, p<0.031) and the PP group (10%) (OR=2.17, 95% CI=1.226–3.853, p<0.009) throughout the whole duration of the trial. In what concerns responsiveness, a significantly higher number of responders were registered in the GP group compared to the AP and the PP groups in the first three months of treatment, but this outcome did not persist afterwards.ConclusionIn terms of its predictive value at first episode schizophrenic patients, SCP seems to be reliable for treatment completion, but has a limited utility in what concerns responsiveness to treatment. This finding suggests the necessity of creating a prediction model potentially including, besides SCP, other measurement-based variables.

P.739 Use of cannabis, alcohol and other substances in mentally ill offenders-data from Northern Greece

Studies and meta-analyses investigating the influence of substance use disorder (SUD) (substance abuse or dependence) on psychopathology and neurocognitive function in schizophrenia patients have revealed controversial results. Most studies did only have small samples and did not focus exclusively on first-episode schizophrenia patients.In a post-hoc analysis of the European First Episode Schizophrenia Trial (EUFEST) psychopathology and cognitive performances of patients with (FE-SUD, N = 119, consisting of N = 88 patients with persisting SUD at baseline and N = 31 patients with previous SUD) and without SUD (FE-non-SUD, N = 204) were compared at baseline and 6 months follow-up. Neurocognitive assessment included the Rey Auditory Verbal Learning Test (RAVLT); Trail Making Tests A and B (TMT), Purdue Pegboard and Digit-Symbol Coding.In total 31.1% of patients reported SUD, and 22.2% of patients used cannabis. There were no significant differences between patients with and without SUD concerning PANSS scores, extrapyramidal motor symptoms or neurocognitive measures except better performance in psychomotor speed (TMT-A, p = 0.033, Cohen's d = 0.26) in patients with SUD at 6 months follow-up. Interestingly, SUD patients with ongoing substance use at follow-up showed elevated positive symptoms (PANSS positive score, p = 0.008, Cohen's d = 0.84) compared to those who abstained. PANSS scores at baseline were increased in patients with an onset of SUD before the age of 16 years. In addition we found a correlation between longer duration of cannabis use and higher cognitive performance as well as reduced symptom improvement and more extrapyramidal motor symptoms in patients with higher frequency of cannabis consumption.FE-SUD and FE-non-SUD show similar psychopathology and neuropsychological performances at baseline and during the first 6 months of antipsychotic treatment.

M81 - SCHIZOPHRENIA POLYGENIC RISK SCORE PREDICTS ANTIPSYCHOTIC TREATMENT RESPONSE IN PATIENTS WITH FIRST EPISODE PSYCHOSIS

Background The genetic basis of antipsychotic drug efficacy is likely polygenic in nature. Genetic risks of schizophrenia may also be related to antipsychotic drug response. The Psychiatric Genomics Consortium (PGC) Genome-Wide Association Study (GWAS) provided evidence of association with schizophrenia risk for many Single Nucleotide Polymorphism (SNP) across the genome. We examined whether Polygenic Risk Scores (PRS) based on the PGC GWAS are predictive of antipsychotic efficacy in four cohorts of patients with first episode psychosis (total n=510): 1) Zucker Hillside Hospital First Episode schizophrenia trial (ZHH-FE), 2) European First Episode Schizophrenia Trial (EUFEST), 3) Spanish First Episode Psychosis study (SFEP), and 4) the clinical trial as part of the Center for Intervention Development and Applied Research at ZHH (CIDAR). Methods The discovery cohort was the ZHH-FE with 77 patients (mixed ethnicity) randomized to risperidone or olanzapine. Three replication cohorts were: 1) EUFEST with 141 patients (all Caucasian) randomized to five antipsychotics; 2) SFEP with 192 patients (all Caucasian) on various antipsychotics; and 3) CIDAR with 100 patients (mixed ethnicity) randomized to risperidone or aripiprazole. Genotyping was performed using the Illumina Omni-1Quad (EUFEST and ZHH-FE) or Illumina Infinium HumanOmniExpressExome platform (CIDAR and SFEP). SNP imputation was conducted with IMPUTE2 against the full 1000 Genomes v3 reference panel. PRS was computed based on the results of the PGC GWAS using PRSice software for the discovery cohort with thresholds at PT Results Hierarchical linear regression was performed on the 3-month symptom score with the PRS as the predictor while controlling for age, sex, and baseline symptom score. Genomic principal component scores were also covaried to control for population stratification for ZHH-FE and CIDAR. In the ZHH-FE cohort, higher PRS at the thresholds of PT Discussion These findings suggest that polygenic risk scores for schizophrenia may also be related to antipsychotic drug response. Patients with higher polygenic risk scores tended to have less improvement with antipsychotic drug treatment. Further analysis is needed to elucidate a more refined genomic profile for antipsychotic drug response.

O9.7. INDIVIDUALIZED LONG-TERM OUTCOME PREDICTION OF PSYCHOSIS IN AN OBSERVATIONAL STUDY: A MACHINE LEARNING APPROACH

BackgroundSchizophrenia and related disorders have heterogeneous outcomes. Predicting long-term psychosis outcome may be helpful in improving treatment decision making. The aim of our study was to develop and validate a long-term outcome prediction model of psychosis in individual patients. Many studies have shown that outcome is related to symptoms, demographic, clinical, cognitive, genetic and environmental data – at the level of correlations. We hypothesized that, using machine learning (ML), it is possible to predict individual long-term outcome based on patterns that are present in these data at baseline. Second, we test if variables that were recently found to be predictive of short-term outcome (European First Episode Schizophrenia Trial (EUFEST), Koutsouleris et al, 2016) can yield accurate long-term outcome predictions in our sample.MethodsThis study included 523 patients (mean (SD) age = 27.6 (7.4) year) from the Genetic Risk and Outcome of Psychosis study. The study extensively assessed patients at baseline, 3- and 6-year follow-up. Outcome was defined in two ways: 1) Symptomatic: being in remission (good outcome) or not in remission (poor outcome), according to the Remission Tool (i.e. a consensus definition which defines remission as maintaining core DSM symptoms, based on Positive and Negative Symptom Scale [PANSS] on a low level during ≥6 months); and 2) Functional, using Global Assessment of Functioning (GAF) scale, divided into good (GAF≥65) and poor (GAF <65) outcome. A support vector machine was trained to predict outcome based on (combinations of) the following sets of baseline data: PANSS, clinical and demographic variables, substance use, neurocognitive/ social cognitive tasks, premorbid adjustment, need of care items (CANSAS), extrapyramidal symptoms, genetic features, environmental variables; and the sets of predictors from 4- and 52-week GAF-based outcome prediction models from the EUFEST study. We trained full and leaner models, using recursive feature elimination (RFE). We tested performance of outcome prediction models using nested cross-validation, i.e., predicting outcome in patients not part of the training set.Results6-year functional outcome (i.e. GAF status) was best predicted by a multi-modal model based on baseline PANSS, CANSAS, clinical and demographic variables, using RFE: 75% of the patients was correctly predicted. Significant predictions using single-modal models were obtained for baseline PANSS (62.7%), clinical (60.9%) and CANSAS predictors (58.0%). For functional outcome (GAF) at 6 years, also baseline PANSS, clinical and CANSAS related features produced highest accuracies (61.1%, 63.1% and 59.3% resp.). Classification of symptomatic and functional outcome at 3 years yielded comparable results. Replication using the best scoring predictors of 4 and 52 weeks outcome in the EUFEST study resulted in accuracies of 61.5% and 56.5% for remission 3-year outcome; 61.6% and 61.0% for remission 6-year outcome; 60.1% and 57.7% for GAF 3-year outcome; 62.3% and 64.6% for GAF 6-year outcome.DiscussionOur results show that predicting long-term symptomatic and functional outcome can be done with reasonable accuracies of up to 75%. Training a ML algorithm revealed that PANSS, clinical and need of care features predicted our multiple endpoints best. Interestingly, EUFEST predictors included these three types of data as a main part of best performing predictors. We showed that these short-term outcome predictors are, to certain extent (up to 65%), also predictive of long-term outcome. Our study is a promising step in pursuit of personalized medicine applicability in mental care institutes. However, our model needs replication in independent samples.

PROLACTIN LEVEL IN PATIENTS WITH FIRST EPISODE SCHIZOPHRENIA TREATED FOR ONE YEAR WITH ATYPICAL ANTIPSYCHOTICS.

Atypical antipsychotics (AAs) are the first-line treatments for schizophrenia, schizoaffective disorder and bipolar disorder. However, they are now extensively utilized as off label in a myriad of diseases despite their frequently serious metabolic side-effects and hyperprolactinemia. The purpose of our study was to observe long-term (one year) prolactin level change in first episode schizophrenia patients treated with one of the four AAs: olanzapine, quetiapine, amisulpride, ziprasidone. This study is an analysis of the prolactin level associated with the atypical antipsychotics used in European First Episode Schizophrenia Trial (EUFEST) study. Seventy-three first episode schizophrenia patients from the 113 patients, randomized to one of the four AAs treatment arms. Prolactin level was obtained at baseline, 6 and 12 months for all the four AAs. Analyses have been done for each antipsychotic separately for each sex. For the male patients neither of the four antipsychotics have been associated with a statistically significant increase of prolactin level in the entire study (p>0.05). In case of the female patients, treatment with olanzapine (p=.021) and ziprasidone (p=.005) has been associated with a decrease of prolactin level in one year compared with baseline. In both men and women, the administration of these four AAs is not associated with the increase of prolactin levels, moreover, in women's case, there is a reduction of prolactin values at administration of Olanzapine and Ziprasidone. These results are optimistic, suggesting that long term administration of these antipsychotics is safe regarding prolactin level.

Predictors of discontinuation of antipsychotic medication and subsequent outcomes in the European First Episode Schizophrenia Trial (EUFEST)

BackgroundThis study had two aims: to describe patients suffering from first-episode schizophrenia who had stopped taking any antipsychotic medication, and to gain information on the predictors of successful discontinuation. MethodsWe investigated data from the European First Episode Schizophrenia Trial (EUFEST). From the 325 patients included, 15.7% discontinued all antipsychotic medication. In a first analysis, clinical and sociodemographical predictors of discontinuing any antipsychotic medication were identified, using Cox regression. In the second analysis, logistic regression was used to determine variables associated with those patients who had stopped taking antipsychotic medication and had a favourable outcome, i.e., successful discontinuation. A good outcome was defined as a) having had no relapse within the whole observation period (80.6%), and b) having had no relapse and symptomatic remission at 12-month-follow-up (37.2%). ResultsCox regression revealed that a higher proportion of patients from Western European countries and Israel stopped antipsychotic medication than from Central and Eastern European countries, that relapse was associated with discontinuation, and that discontinuers had lower compliance and higher quality of life. Predictors of successful discontinuation differed with the outcome definition used. Using definition b), successful discontinuers had a better baseline prognosis and better baseline social integration. Using definition a), successful discontinuers more often were from Western European countries. ConclusionsRegion and clinical factors were associated with discontinuation. Prognosis and social integration played an important role in predicting successful discontinuation. As this study had several limitations, for example the observational design regarding discontinuation, further studies are needed to identify predictors of successful discontinuation.

WEIGHT GAIN AND ANTIPSYCHOTICS. DATA FROM EUFEST STUDY.

Schizophrenia is a chronic disease most frequently necessitating lifelong antipsychotic treatment. Selecting which antipsychotic is to be prescribed in an individual schizophrenia patient represents an important clinical decision that need to take into account efficacy and side effects. Evaluating weight gain related with one year antipsychotic treatment in antipsychotic naive first-episode schizophrenia patients. This study is an analysis of weight gain associated with typical or atypical antipsychotics used in European First Episode Schizophrenia Trial (EUFEST) study. 113 first episode naïve antipsychotic schizophrenia patients included in EUFEST - Romanian cohort, who were randomized to one of the 5 treatment arms. Weight was obtained at baseline, 3, 6, 9 and 12 months for the 5 antipsychotics (typical-Haloperidol; atypical-Olanzapine, Amisulpride, Ziprasidone, Quetiapine). There are no statistically significant differences between groups treated with typical or atypical antipsychotics or between any individual antipsychotics concerning weight gain during the study. Weight gain was the highest in the first 3 months (57.49%) for all the studied neuroleptics. At the end of the study, the less increase was observed with ziprasidone (3.87 kg) and the highest with olanzapine (9.83 kg). Increase in weight has taken place for each individual neuroleptic, but also as a group (all neuroleptics) in the first three months (57.49%). Therefore, we should address the issue of weight gain with great care, especially in first period of antipsychotic administration, in order to fast deploy intervention tailored to maintain pre-treatment weight.

Hostility in schizophrenia: An integrated analysis of the combined Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and the European First Episode Schizophrenia Trial (EUFEST) studies

Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study enrolled a sample of 1493 chronic schizophrenia patients. The European First Episode Schizophrenia Trial (EUFEST) enrolled 498 patients. We have combined these two samples to study the effects of hostility on study discontinuation as well as to examine correlates and predictors of hostility. Individual data from 1154 patients with complete data were used for analyses. Survival analysis demonstrated that higher hostility was associated with earlier all-cause treatment discontinuation. Furthermore, regression analysis indicated that increased hostility was associated with more severe positive symptoms, lower adherence to pharmacological treatment, younger age, impaired insight, and more drug or alcohol consumption. The clinical implications of the results point to the importance of establishing therapeutic alliance while managing patient's symptoms of hostility with antipsychotics such as olanzapine combined with psychosocial interventions to improve insight and reduce substance use.

Gender differences in the treatment of first-episode schizophrenia: Results from the European First Episode Schizophrenia Trial

Gender differences in the response to antipsychotic treatment have been detected in the past, but not studied in great detail. The results of the European First-Episode Schizophrenia Trial (EUFEST) were analyzed with a focus on gender differences in the response to randomized treatment of first-episode schizophrenia. A total of 498 patients (298 men and 200 women) were randomly assigned by a web-based online system to open-label treatment with haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone. Treatment response was evaluated using the positive and negative syndrome scale (PANSS). Data were collected at baseline and then prospectively for one year. Baseline characteristics (age and proportion of patients assigned to individual antipsychotics) were the same between the male and female patients with the exception of ziprasidone: significantly fewer men, proportionately, were prescribed ziprasidone. There was no significant difference between genders between the initial total PANSS and subscale scores. A significant interaction between time and gender was found, with more robust PPANSS and TPANSS score improvement in women during the course of treatment. Of all of the antipsychotics used, only olanzapine led to significantly greater improvement in the total PANSS score in women during the follow-up period. Gender differences should be given more attention in research and clinical practice. Their causes require clarification, and future strategies for dealing with them may be considered in early intervention programs and guidelines.

Treatment adherence in schizophrenia: A patient-level meta-analysis of combined CATIE and EUFEST studies

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) obtained a sample of 1493 chronic schizophrenia patients. The European First Episode Schizophrenia Trial (EUFEST) studied a sample of 498 patients. We have combined these two samples to study the predictors and correlates of adherence to treatment. Here we report on adherence to pharmacological treatment at the six and twelve month assessments of these trials with a combined subsample of 1154 schizophrenia patients. Individual patients׳ data were used for analyses. We used logistic regression to examine the effects of substance use, akathisia, parkinsonism, dyskinesia, hostility, and insight on pharmacological adherence. The results showed that reduced adherence to pharmacological treatment was associated with substance use (p=0.0003), higher levels of hostility (p=0.0002), and impaired insight (p<0.0001). Furthermore, poor adherence to study medication was associated with earlier discontinuation in the combined data. The clinical implications of the results point to the importance of routine assessments and interventions to address patients׳ insight and comorbid substance use and the establishment of therapeutic alliance.

Differential effects of antipsychotic drugs on insight in first episode schizophrenia: Data from the European First-Episode Schizophrenia Trial (EUFEST)

Although antipsychotics are widely prescribed, their effect of on improving poor illness insight in schizophrenia has seldom been investigated and therefore remains uncertain. This paper examines the effects of low dose haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on insight in first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. The effects of five antipsychotic drugs in first episode psychosis on insight were compared in a large scale open randomized controlled trial conducted in 14 European countries: the European First-Episode Schizophrenia Trial (EUFEST). Patients with at least minimal impairments in insight were included in the present study (n=455). Insight was assessed with item G12 of the Positive and Negative Syndrome Scale (PANSS), administered at baseline and at 1, 3, 6, 9, and 12 months after randomization. The use of antipsychotics was associated with clear improvements in insight over and above improvements in other symptoms. This effect was most pronounced in the first three months of treatment, with quetiapine being significantly less effective than other drugs. Effects of spontaneous improvement cannot be ruled out due to the lack of a placebo control group, although such a large spontaneous improvement of insight would seem unlikely.

Do Antipsychotics Affect Insight in Psychosis Differentially? Data From the EUFEST Trial.

Background Although antipsychotics are widely prescribed, their effect of on improving poor illness insight in schizophrenia has seldom been investigated and therefore remains uncertain. This paper examines the effects of low dose haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on insight in first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. Method The effects of five antipsychotic drugs in first episode psychosis on insight were compared in a large scale open randomized controlled trial conducted in fourteen European countries: the European First-Episode Schizophrenia Trial (EUFEST). Patients with at least minimal impairments in insight were included in the present study (n=455). Insight was assessed with item G12 of the Positive and Negative Syndrome Scale (PANSS), administered at baseline and at 1, 3, 6, 9, and 12 months after randomization. Results The use of antipsychotics was associated with clear improvements in insight, independent of other symptoms. This effect was most pronounced in the first three months of treatment, with quetiapine being significantly less effective than other drugs. Conclusions Use of antipsychotics was associated with an improvement in insight, over and above their effects on other symptoms of schizophrenia. Effects of spontaneous improvement cannot be ruled out due to the lack of a placebo control group, although such a large spontaneous improvement seems unlikely. Notably, the improvement of insight was less pronounced for quetiapine compared to haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone.

Extrapyramidal symptoms during treatment of first schizophrenia episode: Results from EUFEST

The European First Episode Schizophrenia Trial (EUFEST) included first-episode schizophrenia patients, assessing the efficacy of five antipsychotic drugs (haloperidol, amisulpride, olanzapine, quetiapine and ziprasidone) over one year. Baseline frequency of extrapyramidal symptoms (EPS) in this group of patients (n=490) was as follows: parkinsonism 10.8%, akathisia 10.0%, dystonia 1.8%, and dyskinesia 0.6%. The frequency of parkinsonism at baseline was greater in patients with a brief prior exposure to antipsychotics (≤2 weeks) compared with antipsychotic-naïve ones, and was positively correlated with the intensity of negative symptoms and negatively with depressive symptoms. After one month of treatment, the increase of parkinsonism was highest in patients receiving haloperidol (+13%), that of akathisia in patients treated with ziprasidone (+14%), and 10.1% of the patients were taking anticholinergic drugs, most frequently in the haloperidol group (24%). In 291 patients remaining on treatment after one year, both parkinsonism and akathisia had decreased: the frequency of parkinsonism was 3%, highest in the haloperidol group (9.1%), that of akathisia was 3%, highest in the quetiapine group (7.5%), and 4% of patients were taking anticholinergic drugs, most frequently those receiving haloperidol (10.5%). The results obtained suggest that in first-episode schizophrenia patients during the first year of antipsychotic treatment (in this case amisulpride, haloperidol in low doses, olanzapine, quetiapine and ziprasidone), EPS were present as manageable clinical problems.

Effectiveness of antipsychotic drugs against hostility in patients with schizophrenia in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study – ADDENDUM

Introduction Aggressive behavior can be a dangerous complication of schizophrenia. Hostility is related to aggression. This study aimed to compare the effects of olanzapine, perphenazine, risperidone, quetiapine, and ziprasidone on hostility in schizophrenia. Methods We used the data that were acquired in the 18-month Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. We analyzed the scores of the Positive and Negative Syndrome Scale (PANSS) hostility item in a subset of 614 patients who showed at least minimal hostility (a score ≥ 2) at baseline. Results The primary analysis of hostility indicated an effect of difference between treatments (F 4,1487 = 7.78, P Discussion Our results are consistent with those of a similar post - hoc analysis of hostility in first-episode subjects with schizophrenia enrolled in the European First-Episode Schizophrenia Trial (EUFEST) trial, where olanzapine demonstrated advantages compared with haloperidol, quetiapine, and amisulpride. Conclusion Olanzapine demonstrated advantages in terms of a specific antihostility effect over the other antipsychotics tested in Phase 1 of the CATIE trial.

Metabolic risk factors in first-episode schizophrenia: baseline prevalence and course analysed from the European First-Episode Schizophrenia Trial

Available data on antipsychotic-induced metabolic risks are often constrained by potential confounding effects due to prior antipsychotic treatment. In this study, we assessed the baseline prevalence of metabolic abnormalities and changes following treatment with five commonly-used antipsychotic drugs (haloperidol, amisulpride, olanzapine, quetiapine or ziprasidone) in first-episode, partially antipsychotic-naive patients with schizophrenia in the European first-episode schizophrenia trial (EUFEST). Overall baseline prevalence of metabolic syndrome (MetS) was 6.0%, with similar rates observed in the antipsychotic-naive patients (5.7%, 9/157) and in the other patients with only a brief prior exposure to antipsychotics (6.1%, 20/326). These results are consistent with the MetS prevalence rate estimated in a general population of similar age. Examination of individual risk factors showed 58.5% of subjects had one or more elevated metabolic risks at baseline: 28.5% demonstrated suboptimal HDL; 24.2% hypertension; 17.7% hypertriglyceridemia; 8.2% abdominal obesity; 7.3% hyperglycaemia. Increase in body weight (kg/month) occurred in patients treated with haloperidol (0.62 S.E. 0.11), amisulpride (0.76 S.E. 0.08), olanzapine (0.98 S.E. 0.07) and quetiapine (0.58 S.E. 0.09), which was significantly greater than that in the ziprasidone group (0.18 S.E. 0.10). The incidence rate of new diabetes cases over a 52-wk follow-up period was 0.82% (4/488). More patients experienced worsening rather than improvement of hypertriglyceridemia or hyperglycaemia in all treatment groups. Our findings suggest that in first-episode, partially antipsychotic-naive patients, the baseline prevalence rate of MetS appears to be no higher than that in the general population, but serious underlying individual risk factors nevertheless existed.

Hyperprolactinemia in antipsychotic-naive patients with first-episode psychosis

Hyperprolactinemia is frequent in patients with schizophrenic psychoses. It is usually regarded as an adverse effect of antipsychotics but has recently also been shown in patients without antipsychotic medication. Our objective was to test whether hyperprolactinemia occurs in antipsychotic-naive first-episode patients (FEPs). In the framework of the European First Episode Schizophrenia Trial (EUFEST), 249 out of 498 FEPs were eligible for this study, of whom 74 were antipsychotic naive. All patients were investigated regarding their serum prolactin levels with immunoassays standardized against the 3rd International Reference Standard 84/500. Twenty-nine (39%) of the 74 antipsychotic-naive patients showed hyperprolactinemia not explained by any other reason, 11 (50%) of 22 women and 18 (35%) of 52 men. Hyperprolactinemia may be present in patients with schizophrenic psychoses independent of antipsychotic medication. It might be stress induced. As enhanced prolactin can increase dopamine release through a feedback mechanism, this could contribute to explaining how stress can trigger the outbreak of psychosis.

Comorbid substance abuse in first-episode schizophrenia: Effects on cognition and psychopathology in the EUFEST study

Studies and meta-analyses investigating the influence of substance use disorder (SUD) (substance abuse or dependence) on psychopathology and neurocognitive function in schizophrenia patients have revealed controversial results. Most studies did only have small samples and did not focus exclusively on first-episode schizophrenia patients. MethodIn a post-hoc analysis of the European First Episode Schizophrenia Trial (EUFEST) psychopathology and cognitive performances of patients with (FE-SUD, N=119, consisting of N=88 patients with persisting SUD at baseline and N=31 patients with previous SUD) and without SUD (FE-non-SUD, N=204) were compared at baseline and 6months follow-up. Neurocognitive assessment included the Rey Auditory Verbal Learning Test (RAVLT); Trail Making Tests A and B (TMT), Purdue Pegboard and Digit-Symbol Coding. ResultsIn total 31.1% of patients reported SUD, and 22.2% of patients used cannabis. There were no significant differences between patients with and without SUD concerning PANSS scores, extrapyramidal motor symptoms or neurocognitive measures except better performance in psychomotor speed (TMT-A, p=0.033, Cohen's d=0.26) in patients with SUD at 6months follow-up. Interestingly, SUD patients with ongoing substance use at follow-up showed elevated positive symptoms (PANSS positive score, p=0.008, Cohen's d=0.84) compared to those who abstained. PANSS scores at baseline were increased in patients with an onset of SUD before the age of 16years. In addition we found a correlation between longer duration of cannabis use and higher cognitive performance as well as reduced symptom improvement and more extrapyramidal motor symptoms in patients with higher frequency of cannabis consumption. ConclusionsFE-SUD and FE-non-SUD show similar psychopathology and neuropsychological performances at baseline and during the first 6months of antipsychotic treatment.

E.05.03 The unmet needs in the treatment of alcohol dependence

Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study enrolled a sample of 1493 chronic schizophrenia patients. The European First Episode Schizophrenia Trial (EUFEST) enrolled 498 patients. We have combined these two samples to study the effects of hostility on study discontinuation as well as to examine correlates and predictors of hostility. Individual data from 1154 patients with complete data were used for analyses. Survival analysis demonstrated that higher hostility was associated with earlier all-cause treatment discontinuation. Furthermore, regression analysis indicated that increased hostility was associated with more severe positive symptoms, lower adherence to pharmacological treatment, younger age, impaired insight, and more drug or alcohol consumption. The clinical implications of the results point to the importance of establishing therapeutic alliance while managing patient's symptoms of hostility with antipsychotics such as olanzapine combined with psychosocial interventions to improve insight and reduce substance use.

Treatment of depression in first episode of schizophrenia: Results from EUFEST

Depressive symptomatology is an important target of treatment in first episode schizophrenia. This reanalysis of the European First Episode Schizophrenia Trial (EUFEST) describes the depressive symptomatology and the effect of antipsychotic treatment in patients suffering from first episode schizophrenia and schizophreniform disorder randomized to treatment with low dose haloperidol (n=103), amisulpride (n=104), olanzapine (n=105), quetiapine (n=104) or ziprasidone (n=82) for one year. At baseline, the mean score on the Calgary Depression Scale for Schizophrenia (CDSS) was 5.1 (±4.9) with 38.3% of patients having a CDSS score≥6, i.e. clinically relevant depressive symptom severity. During treatment depression scores decreased, the mean CDSS score being 1.1 (±2.1) and 3.0% of patients having a CDSS≥6 at 52 weeks. The proportion of patients using antidepressants during the complete trial was 18.5% in the haloperidol group, 28.6% in the olanzapine group compared to 5.8% in the quetiapine group, 12.5% in the amisulpride group, and 9.8% in the ziprasidone group. There were no differences over time in the probability of being depressed (CDSS≥6) between the 5 treatment groups after adjustment for antidepressant use, nor in a sub analysis of patients who did not take any antidepressant. Depression scores at baseline or during the trial had no effect on treatment discontinuation or on the reduction of positive symptoms. In summary, the results of EUFEST did not demonstrate a differential effect of the antipsychotics studied on depressive symptomatology in patients with first episode schizophrenia.

Mid-Term and Long-Term Efficacy and Effectiveness of Antipsychotic Medications for Schizophrenia

Our aim in this article is 2-fold: first, to examine the mid-term to long-term data on efficacy, from controlled and naturalistic and other studies, in order to determine if they are consistent with the quantitative meta-analyses of mostly short-term, randomized controlled trials Our second (and most important) aim is to use these and other data to provide guidance about the potential relationship of these differences among antipsychotics to the individual patient's own experience with antipsychotic drugs in the process of shared decision-making with the patients and their significant others. A search of PubMed, Embase, and PsychINFO was conducted for articles published in English between January 1, 1999, and April 2011, using the search terms double-blind AND randomized AND olanzapine AND (ziprasidone OR risperidone OR quetiapine OR haloperidol OR fluphenazine OR perphenazine OR aripiprazole). Studies with a duration 3 months or longer, including patients with schizophrenia or schizoaffective disorder, reporting survival analysis for all-cause discontinuation and relapse or dropout due to poor efficacy were selected. We extracted the number of patients relapsed due to poor efficacy and hazard rates for relapses. Overall, the efficacy patterns of both controlled effectiveness and observational long-term studies closely parallel the efficacy observed in the short-term, controlled studies. The results of Phase 1 Clinical Antipsychotic Trials of Intervention Effectiveness are very similar to, but not identical with, the controlled short-term efficacy studies, the European First-Episode Schizophrenia Trial, and naturalistic studies. The mid-term and long-term data suggest that olanzapine is more effective than risperidone and that both of these are better than the other first- and second-generation antipsychotics except for clozapine, which is the most efficacious of all. Further large differences emerged regarding the specific mid-term and long-term safety profiles of individual antipsychotics. Despite intraclass differences and the complexities of antipsychotic choice, the second-generation antipsychotics are important contributions not only to the acute phase but, more importantly, to the maintenance treatment of schizophrenia.