Schizophrenia In Europe Research Articles

FAMILY-CENTERED COLLABORATIVE CARE FOR PATIENTS WITH CHRONIC MENTAL ILLNESS: A NARRATIVE LITERATURE REVIEW

IntroductionChronic mental illnesses are long-lasting and recurring, require continuous care as well as an integrated and collaborative approach to organize the care. This study sought to examine whether family center collaborative care is an acceptable treatment option for individuals with chronic mental illness.ObjectivesIs the family-centered collaborative care suitable for patients with chronic mental illness?MethodsFrom the years 2000 to 2021, ten electronic databases relating to family-centered collaborative care for mental illness were searched adopting PRISMA’s checklistResultsAfter systematic search, 27 articles and a thesis were found. According to moderate to high quality qualitative research, family-centered collaborative care was considered acceptable intervention, though a few studies supporting it.ConclusionsThis study examines theoretical, methodological, and practical considerations as a basis for more robust data collection based on individual experiences and evidence-based practice.Reference(s)1.Wittchen, H.-U., et al., The size and burden of mental disorders and other disorders of the brain in Europe 2010. European neuropsychopharmacology, 2011. 21(9): p. 655-679.2.CUTLER, J.L., Kaplan and Sadock’s synopsis of psychiatry. 2016, LWW.3.Thornicroft, G., et al., The personal impact of schizophrenia in Europe. Schizophrenia research, 2004. 69(2-3): p. 125-132.4.Vigo, D., G. Thornicroft, and R. Atun, Estimating the true global burden of mental illness. The Lancet Psychiatry, 2016. 3(2): p. 171-178.Disclosure of InterestNone Declared

Efficacy of oral versus long-acting antipsychotic treatment in patients with early-phase schizophrenia in Europe and Israel: a large-scale, open-label, randomised trial (EULAST)

Schizophrenia is a severe psychiatric disorder with periods of remission and relapse. As discontinuation of antipsychotic medication is the most important reason for relapse, long-term maintenance treatment is key. Whether intramuscular long-acting (depot) antipsychotics are more efficacious than oral medication in preventing medication discontinuation is still unresolved. We aimed to compare time to all-cause discontinuation in patients randomly allocated to long-acting injectable (LAI) versus oral medication. EULAST was a pragmatic, randomised, open-label trial conducted at 50 general hospitals and psychiatric specialty clinics in 15 European countries and Israel. Patients aged 18 years and older, with DSM-IV schizophrenia (as confirmed by the Mini International Neuropsychiatric Interview 5 plus) and having experienced their first psychotic episode from 6 months to 7 years before screening, were randomly allocated (1:1:1:1) using block randomisation to LAI paliperidone, LAI aripiprazole, or the respective oral formulations of these antipsychotics. Randomisation was stratified by country and duration of illness (6 months up to 3 years vs 4 to 7 years). Patients were followed up for up to 19 months. The primary endpoint was discontinuation, regardless of the reason, during 19 months of treatment. We used survival analysis to assess the time until all-cause discontinuation in the intention-to-treat (ITT) group, and per protocol analyses were also done. This trial is registered with ClinicalTrials.gov, NCT02146547, and is complete. Between Feb 24, 2015, and Dec 15, 2018, 533 individuals were recruited and assessed for eligibility. The ITT population included 511 participants, with 171 (33%) women and 340 (67%) men, and a mean age of 30·5 (SD 9·6) years. 410 (80%) of 511 participants were White, 35 (7%) were Black, 20 (4%) were Asian, and 46 (9%) were other ethnicity. In the combined oral antipsychotics treatment group of 247 patients, 72 (29%) patients completed the study and 175 (71%) met all-cause discontinuation criteria. In the combined LAI treatment arm of 264 patients, 95 (36%) completed the study and 169 (64%) met the all-cause discontinuation criteria. Cox regression analyses showed that treatment discontinuation for any cause did not differ between the two combined treatment groups (hazard ration [HR] 1·16, 95% CI 0·94-1·43, p=0·18). No significant difference was found in the time to all-cause discontinuation between the combined oral and combined LAI treatment groups (log rank test χ2=1·87 [df 1]; p=0·17). During the study, 121 psychiatric hospitalisations occurred in 103 patients, and one patient from each of the LAI groups died; the death of the patient assigned to paliperidone was assessed to be unrelated to the medication, but the cause of other patient's death was not shared with the study team. 86 (25%) of 350 participants with available data met akathisia criteria and 70 (20%) met parkinsonism criteria at some point during the study. We found no substantial advantage for LAI antipsychotic treatment over oral treatment regarding time to discontinuation in patients with early-phase schizophrenia, indicating that there is no reason to prescribe LAIs instead of oral antipsychotics if the goal is to prevent discontinuation of antipsychotic medication in daily clinical practice. Lundbeck and Otsuka.

Real-world treatment patterns and outcomes in patients initiating lurasidone for the treatment of schizophrenia in Europe

IntroductionLurasidone is a second-generation antipsychotic shown to have a lower risk of weight gain and a lower incidence of metabolic adverse events compared with some medications in the same class.ObjectivesTo describe treatment patterns, clinical outcomes and adverse drug reactions (ADRs) over 12 months following lurasidone initiation in patients with schizophrenia.MethodsThis was a multi-centre observational study involving data collection from patients’ medical records, conducted in seven mental health centres in the United Kingdom (UK) and Switzerland. The study included patients aged ≥18 years who initiated lurasidone after 1 January 2016 for the treatment of schizophrenia. Data were collected from medical records both retrospectively and prospectively using a standardised data collection form. Data collected included patient characteristics, treatment history, lurasidone regimens, clinical outcomes and ADRs.ResultsForty-eight patients participated in the study. The median (interquartile range [IQR]) age at lurasidone initiation was 33.5 (25.5-50.3) years and 31 (65%) patients were male. The median (range) lurasidone starting dose was 37 mg daily (9.3–148 mg). Thirty-eight (79%) patients continued lurasidone for the entire 12-month follow-up period. Among the 14 (29%) patients with documented relapse, the median (IQR) time to relapse was 3.4 (1.5–7.9) months. Five ADRs were recorded in patient notes judged as related to lurasidone: agitation, nausea, akathisia, somnolence and vomiting (one patient each).ConclusionsIn this real-world study of patients with schizophrenia in the UK and Switzerland, 79% of patients continued lurasidone for at least 12 months, and ADRs were reported rarely in patient notes.DisclosureThis study was sponsored by CNX Therapeutics Ltd (formerly Sunovion Pharmaceuticals Europe Ltd). AJ is an employee of CNX Therapeutics. MA is an employee of OPEN HEALTH who was contracted by CNX Therapeutics for data analysis and medical writing.

Efficacy and safety of paliperidone palmitate 6-month versus paliperidone palmitate 3-month long-acting injectable in patients with schizophrenia in Europe

Efficacy and safety of paliperidone palmitate 6-month versus paliperidone palmitate 3-month long-acting injectable in patients with schizophrenia in Europe

Baseline Levels of C-Reactive Protein and Proinflammatory Cytokines Are Not Associated With Early Response to Amisulpride in Patients With First Episode Psychosis: The OPTiMiSE Cohort Study

Abstract Patients with a First-Episode of Psychosis (FEP) exhibit low-grade inflammation as demonstrated by elevated levels of C-reactive protein (CRP) and proinflammatory cytokines. The primary goal of this study was to investigate the association between proinflammatory biomarkers and clinical outcomes in unmedicated FEP patients. We used clinical data and biological samples from 289 FEP patients participating to the Optimization of Treatment and Management of Schizophrenia in Europe (OPTIMISE) clinical trial. Patients were assessed at baseline and 4–5 weeks after treatment with amisulpride. Baseline serum levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and CRP were measured. We first used multivariable regression to investigate the association between each of the 4 tested biomarkers and the following clinical outcomes: Positive and Negative Syndrome Scale (PANSS), Calgary Depression Score for Schizophrenia (CDSS), remission according to Andreasen’s criteria, and Serious Adverse Events (SAEs). As a complementary approach, we used an unsupervised clustering method to stratify patients into an “inflamed” or a “non-inflamed” biotype based on baseline levels of IL-6, IL-8, and TNF-α. We then used linear and logistic regressions to investigate the association between the patient biotype and clinical outcomes. After adjusting for covariates and confounders, we did not find any association between IL-6, IL-8, TNF-α, CRP, or the patient biotype and clinical outcomes. Our results do not support the existence of an association between baseline levels of CRP and proinflammatory cytokines and early response to amisulpride in unmedicated FEP patients. ClinicalTrials.gov Identifier: NCT01248195.

Relationship Between Serum NMDA Receptor Antibodies and Response to Antipsychotic Treatment in First-Episode Psychosis

BackgroundWhen psychosis develops in NMDA receptor (NMDAR) antibody encephalitis, it usually has an acute or subacute onset, and antipsychotic treatment may be ineffective and associated with adverse effects. Serum NMDAR antibodies have been reported in a minority of patients with first-episode psychosis (FEP), but their role in psychosis onset and response to antipsychotic treatment is unclear. MethodsSera from 387 patients with FEP (duration of psychosis <2 years, minimally or never treated with antipsychotics) undergoing initial treatment with amisulpride as part of the OPTiMiSE (Optimization of Treatment and Management of Schizophrenia in Europe) trial (ClinicalTrials.gov number NCT01248195) were tested for NMDAR IgG antibodies using a live cell–based assay. Symptom severity was assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impressions Scale at baseline and again after 4 weeks of treatment with amisulpride. ResultsAt baseline, 15 patients were seropositive for NMDAR antibodies and 372 were seronegative. The seropositive patients had similar symptom profiles and demographic features to seronegative patients but a shorter duration of psychosis (median 1.5 vs. 4.0 months; p = .031). Eleven seropositive and 284 seronegative patients completed 4 weeks of amisulpride treatment: after treatment, there was no between-groups difference in improvement in Positive and Negative Syndrome Scale scores or in the frequency of adverse medication effects. ConclusionsThese data suggest that in FEP, NMDAR antibody seropositivity alone is not an indication for using immunotherapy instead of antipsychotic medications. Further studies are required to establish what proportion of patients with FEP who are NMDAR antibody seropositive have coexisting cerebrospinal fluid inflammatory changes or other paraclinical evidence suggestive of a likely benefit from immunotherapy.

Gene expression and response prediction to amisulpride in the OPTiMiSE first episode psychoses.

A fundamental shortcoming in the current treatment of schizophrenia is the lack of valid criteria to predict who will respond to antipsychotic treatment. The identification of blood-based biological markers of the therapeutic response would enable clinicians to identify the subgroup of patients in whom conventional antipsychotic treatment is ineffective and offer alternative treatments. As part of the Optimisation of Treatment and Management of Schizophrenia in Europe (OPTiMiSE) programme, we conducted an RNA-Seq analysis on 188 subjects with first episode psychosis, all of whom were subsequently treated with amisulpride for 4 weeks. We compared gene expression on total RNA from patients' blood before and after treatment and identified 32 genes for which the expression changed after treatment in good responders only. These findings were replicated in an independent sample of 24 patients with first episode psychosis. Six genes showed a significant difference in expression level between good and poor responders before starting treatment, allowing to predict treatment outcome with a predictive value of 93.8% when combined with clinical features. Collectively, these findings identified new mechanisms to explain symptom improvement after amisulpride medication and highlight the potential of combining gene expression profiling with clinical data to predict treatment response in first episode psychoses.

Cariprazine

Abstract Objective Cariprazine is a new antipsychotic drug approved for the treatment of schizophrenia in Europe in 2017. Clinical studies suggest advantages of cariprazine in comparison to other antipsychotic agents regarding therapeutic effects on “negative symptoms”, antipsychotic-induced weight gain and increased serum prolactin levels. Akathisia was reported to be one of the most common side effects. Currently, however, data from naturalistic treatment settings regarding the efficacy, safety and tolerability of cariprazine are missing. Thus, we report and discuss our clinical experiences with cariprazine regarding efficacy, safety and tolerability in order to provide first treatment data from a naturalistic treatment setting. Material and methods The course of treatment of a series of 3 patients with schizophrenia spectrum disorders and treatment with cariprazine (mono- or combined therapy) is presented and discussed. Results Cariprazine demonstrated sufficient antipsychotic effects in 2 out of 3 cases; however, in 2 out of 3 cases treatment had to be discontinued due to akathisia/agitation; in 1 case, cariprazine monotherapy facilitated successful normalization of elevated prolactin serum levels (due to combined treatment with risperidone and olanzapine). Conclusion(s): In general, experience with cariprazine within a naturalistic treatment setting is in accordance with data from clinical studies, particularly concerning effects on “negative symptoms”, antipsychotic-associated elevation of prolactin serum levels and risk of akathisia. The comparatively high incidence of discontinuation of cariprazine due to akathisia/agitation in our case series may be an effect of polypharmacy which was very common among our three cases. Clinical relevance This case series provides some evidence that safety, tolerability and antipsychotic efficacy of cariprazine in naturalistic treatment settings may be similar to findings from the available clinical studies.

SU82 - RNA SIGNATURE OF TREATMENT RESPONSE IN FIRST-EPISODE PSYCHOSIS

Background Despite nearly fifty years of pharmacological research, the treatment of schizophrenia remains a challenge and clinical outcomes are still far from optimal. One of the major shortcomings in the current treatment of schizophrenia is that we have no valid criteria in clinical practice to predict who will respond to antipsychotic treatment and how long the treatment should be maintained before changing therapeutic strategy. The identification of blood-based biological markers of drug response with a good sensitivity and specificity would enable physicians to use these tests prior to choosing the antipsychotic treatment and therefore help the practitioner in his daily clinical practice. Methods Through a European consortium on Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE), we conducted a transcriptome analysis on 163 subjects with first episode psychosis. Patients were all treated for four weeks with amisulpride. Blood samples were collected at inclusion and after treatment and total RNA was analyzed by RNA-Seq for each patient before and after treatment as well as according to treatment outcome. After quality control, the detection of differentially expressed genes have been achieved using the DESeq. 2 package and in regards to biological processes and symptom improvement, with the aim of characterizing a biological signature of treatment response in first-episode psychosis. Results The transcription level of 10,683 expressed genes has been analyzed in peripheral blood mononuclear cells. We detected 499 and 84 genes that were differentially expressed after 4-week treatment with amisulpride in remitted and non-remitted patients, respectively, showing enrichment in differentially expressed genes in remitters when compared to non-remitters (p=0.02). We also found that for some of these genes, the expression level was significantly correlated with clinical outcome. A second analysis revealed that 39 of the 499 differentially expressed genes had a different expression level before amisulpride treatment between patients who will be in remission after 4-week treatment, suggesting these genes may help in predicting treatment response. Discussion We demonstrated here that amisulpride treatment affects gene expression in peripheral blood mononuclear cells, mainly in patients who will be in remission after four weeks of treatment, and that gene expression may be associated with symptom improvement. Further replications on independent samples are needed to confirm molecular mechanisms associated with clinical outcome and should help both in the identification of biological signatures of treatment response as well as in the development of new therapeutic strategies.

A systematic review of the indirect costs of schizophrenia in Europe.

BackgroundSchizophrenia is a chronic disease associated with significant and long-lasting effects on health, and it is also a social and financial burden, not only for patients but also for families, other caregivers, and the wider society. It is essential to conduct the assessment of indirect costs, to understand all the effects of the disease on society. Our aim is to gain a better understanding of the indirect costs of schizophrenia in Europe.MethodsWe conducted a comprehensive systematic literature review covering EMBASE, Medline, and PsycINFO as well as reviewing Health Technology Assessment databases from different countries. We used a qualitative research synthesis for presenting information, as most of the studies were methodologically diverse, a quantitative analysis would have been impractical.ResultsIndirect cost adjusted to inflation ranged vastly between studies included in the review from 119 Euros to 62, 034 Euros annually. The average proportion of indirect costs of total costs was 44%. Studies highlighted important cost drivers as age, gender, and disease severity, explaining the variation in costs between treatment and patient groups.ConclusionsRegardless of the methodological heterogeneity of the reviewed studies, there was an agreement about the significance of indirect costs of schizophrenia on the society. Considering the relatively high prevalence of schizophrenia in Europe, a need for more cost of illness studies especially from Central Eastern and Southern Europe is suggested.

F161. Proteomic Analysis of Blood Based Samples From the OPTiMiSE (OPtimization of Treatment and Management of Schizophrenia in Europe) Study Point Towards Complement Pathway Protein Changes

F161. Proteomic Analysis of Blood Based Samples From the OPTiMiSE (OPtimization of Treatment and Management of Schizophrenia in Europe) Study Point Towards Complement Pathway Protein Changes

31. OPTIMISE-ING THE TREATMENT OF FIRST-EPISODE SCHIZOPHRENIA

Overall : Even if there have been effective antipsychotic treatments for more than fifty years, the implementation of these treatments in clinical practice is still far from optimal, and a significant amount of patients with schizophrenia show poor outcomes. It is unquestionable that antipsychotics remain the first treatment option for patients with first-episode schizophrenia (FES). However, several questions still demand answer in the field. It is unclear how long we should wait before changing an antipsychotic that has not been fully effective, how long we have to wait before starting clozapine in FES, whether we can identify who will respond better to current treatments using biological markers including neuroimaging, and how to improve adherence and functional prognosis after clinical remission is achieved.OPTiMiSE (‘Optimisation of Treatment and Management of Schizophrenia in Europe’) is an European Consortium funded under the VII Framework Program that addressed these questions in a sample of nearly 500 patients with FES or schizophreniform psychosis and minimal prior exposure to antipsychotics recruited across Europe and Israel. Within an integrative framework, the Consortium aimed at combining clinical, neuroimaging, genetic and biochemical data in a large representative sample to provide answers to these clinically relevant questions and prepare the field for personalised medication strategies as drugs with novel mechanisms of action become available. Results from this study have not yet been published and most of them will be presented for the first time in a Congress.Based on previous results from the EUFEST study, all patients received amisulpride as a first step. For those not achieving remission after 4 weeks, OPTiMiSE compared in a randomised double-blind fashion the option of staying on amisulpride or moving to a drug with a different receptor-binding profile, olanzapine. In those not achieving remission after 6 weeks, clozapine was started. OPTiMiSE thus constitutes the first systematic, large-scale testing of the potential benefits of early switching to an antipsychotic with different characteristics in patients not achieving remission, and the application of clozapine in non-remitting patients within the first 10 weeks of treatment. OPTiMiSE also provides information on the added value of psychosocial interventions to improve treatment adherence, reduce relapses and improve functional outcomes after remission is achieved, through a 1-year follow-up randomised controlled trial testing a web-based program comprising a motivational intervention package, psychoeducation, and electronic medication alerts and updates.OPTiMiSE also collected blood samples for patients participating in the clinical trial and a systematic sample of more than 200 standardised, high-quality, magnetic resonance imaging (MRI) images. Based on this information, OPTiMiSE examined the clinical utility and cost-effectiveness of MRI for screening of underlying organic conditions in FES. In addition, OPTiMiSE also offers novel information on how MRI alterations, genetic and biochemical markers at first presentation of schizophrenia can predict the response to subsequent treatment. For this, OPTiMiSE used two broad strategies—a combination of technology-driven (pharmacogenetics, proteomics, and metabolomics) and hypothesis-driven (neuroimaging, neurochemical, and immune-related) markers.This symposium offers an overview of the main results obtained in the project in all these areas, with special focus on their clinical and research implications.

31.4 GENETIC, IMMUNOLOGICAL AND BIOCHEMICAL MARKERS OF TREATMENT RESPONSE IN SCHIZOPHRENIA

BackgroundOne of the major shortcomings in the current treatment of schizophrenia is that we have no valid criteria in clinical practice to decide which antipsychotic treatment should be chosen first. This is why we need to define a blood-based biological signature of treatment response that can be easily tested at patient bedside and would also help to identify molecular mechanisms of treatment response by determining biological changes associated with symptom improvements.MethodsThrough a European consortium on Optimization of Treatment and Management of Schizophrenia in Europe (FP7, OPTiMiSE), we conducted a clinical trial on treatment response with Amisulpride in 500 subjects with first episode psychosis. For each patient, biological samples (DNA, RNA, plasma and serum) have been collected before treatment and during follow-up visits at weeks 4, 10 and 22, to measure biological changes associated with treatment initiation and with symptoms improvements. We combined multiple high-throughput technologies for transcriptome, genome, metabolome, proteome analyses before and after treatment.ResultsThe transcriptome analysis conducted on 10,683 genes expressed in peripheral mononuclear cells identified significantly more genes differentially expressed after treatment in 112 patients who will be in remission after 4-weeks treatment than in 51 non-remitters. Using interaction network analysis, we identified biological pathways affected by Amisulpride. For some genes, the expression level was significantly correlated with symptom improvement. Moreover, some genes were already differentially expressed before treatment between remitters and non-remitters, suggesting they might be used to predict treatment outcome. In addition, we identified genetic variations associated with gene expression level and thus may explain individual difference in treatment response.In parallel, as recent biological data have suggested a preponderant role of innate and adaptive immune system in the vulnerability to schizophrenia or in antipsychotic treatment response (Fond et al, 2015), we paid a particular attention to the analysis of inflammatory markers and the presence of auto-antibodies in patients’ sera. Circulating autoantibodies against glutamatergic N-methyl-D-aspartate receptor (NMDAR-Ab) have been reported in up to 10% of patients with psychotic disorders. In our study, we demonstrated the advantage of using cutting-edge methods to ascertain the presence of NMDAR-Ab in seropositive patients that cannot be clinically identified ((Jezequel et al, 2017). Indeed, the only clinical characteristics found in NMDAR-Ab seropositive patients, was the high frequency of female patients, the presence of mild neurologic symptoms and signs of antipsychotic intolerance. In addition, using an advanced statistical classification algorithm, we defined clinically-based subgroups of patients who had specific cytokine signature associated to remission after 4-weeks of treatment, suggesting that these markers may be used to predict treatment response.DiscussionAltogether, our multilevel biological approach resulted in the identification of promising biomarkers, which may be used both to predict drug response and remission in first psychosis episode.

O1.7. PROTEOMIC ANALYSIS OF BLOOD BASED SAMPLES FROM THE OPTiMiSE (OPTIMIZATION OF TREATMENT AND MANAGEMENT OF SCHIZOPHRENIA IN EUROPE) STUDY POINT TOWARDS COMPLEMENT PATHWAY PROTEIN CHANGES

BackgroundThe OPTiMiSE (Optimization of Treatment and Management of Schizophrenia in Europe) trial may help in the identification of predictors of treatment response. Medication naïve patients with first episode schizophrenia or schizophreniform disorder were enrolled in the study and treated open-label for a four-week period with amisulpride. PANSS ratings were undertaken at baseline and following the four-week treatment. 30 non-remitters (as defined by the Andreasen criteria) with the worst change in PANSS scores and the 30 remitters with the best change in PANSS scores were selected to represent good and poor outcome groups.MethodsWe compared proteomic markers in serum collected prior to treatment in 30 patients who subsequently showed a good response to amisulpride (“responders”, and 30 patients who did not show a good response (“non-responders”). Serum samples were depleted using High Performance Liquid Chromatography (HPLC) attached to a MARS column to remove the 14 most abundant plasma proteins (albumin, IgG, antitrypsin, IgA, transferrin, haptoglobin, fibrinogen, alpha2-macroglobulin, alpha1-acid glycoprotein, IgM, apolipoprotein AI, apolipoprotein AII, complement C3, and transthyretin). The groups were matched for ethnicity, gender and age.50 µg from each sample were reduced, alkylated, tryptically digested, then zip-tipped to concentrate and purify. Samples were then run for a 90-min gradient on a Thermo Scientific Q- Exactive Hybrid Quadrupole-Orbitrap Mass Spectrometer. Raw MS data were processed by MaxQuant software and searched against the human Uniprot database, for label free quantitation of peptides and proteins. False discovery rates (FDR) were set at 1% for both peptide and protein levels in target/decoy to minimize false positives. The match between runs feature was utilized.ResultsFour hundred and sixty-four protein identifications were obtained. Samples were excluded where >30% of proteins were missing, and we used imputation, where the missingness depends upon a threshold of detection. This left 228 proteins for analysis. Of these, 21 were significantly different between responders and non-responders (p<0.05), one was FDR positive, one at trend FDR level. Pathway analysis (KEGG, David NIH) of the significant proteins determined “complement and coagulation cascades” to be the top pathway affected with six proteins from the list assigned to the pathway. These were CFI, C4A, C6, F9, VWF and SERPING1, all found to be up-regulated and with p-values ranging from 0.002 to 0.044. C6 is a constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response, while CFI belongs to the alternative pathway, C4A belongs to the classical pathway and F9 and VWF play roles in the intrinsic coagulation pathway.DiscussionThese data complement results by Sekar et al., implicating excessive complement activity in the development of schizophrenia. Our data identifies the complement proteins in treatment response and this is also consistent with our previous findings of up-regulation of the complement pathway among those at risk of future psychotic experiences.

Closing the treatment gap: The EPA case study of schizophrenia

IntroductionSchizophrenia still ranks among the first 10 leading causes of disability worldwide. Recent analyses show that there is a considerable treatment gap in schizophrenia in Europe and worldwide.ObjectivesTo provide evidence-based information and give a concise overview of what is needed to overcome the treatment gap in schizophrenia.MethodsUsing a combined approach of systematic review and health economics was used to assess the socioeconomic impact of medical interventions (or the lack of thereof) for schizophrenia.ConclusionsThe case study analysis demonstrates socioeconomic impact and health gains of best practices in specific healthcare interventions for schizophrenia in comparison with the cost burden of current care or non-treatment.Disclosure of interestUnterstützung bei Symposien/Symposia Support– Janssen-Cilag GmbH, Neuss– Aristo Pharma GmbH, Berlin– Lilly Deutschland GmbH, Bad Homburg– Servier Deutschland GmbH, München– Fakultätsmitglied/Faculty Member– Lundbeck International Neuroscience Foundation (LINF), Dänemark

The Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE) Trial: Rationale for Its Methodology and a Review of the Effectiveness of Switching Antipsychotics.

(Reprinted with permission from Schizophrenia Bulletin 2015; 41(3):549-558).

Magnetic resonance imaging and the prediction of outcome in first-episode schizophrenia: a review of current evidence and directions for future research.

Magnetic Resonance Imaging (MRI) measures are promising outcome markers for schizophrenia, since regional frontal and temporal grey matter volumes reductions, and enlargement of the ventricles, have been associated with outcome in this disorder. However, a number of methodological issues have limited the potential clinical utility of these findings. This article reviewed studies that examined brain structure at illness onset as a predictor of outcome, discusses the limitations of the findings, and highlights the challenges that would need to be addressed if structural data are to inform the management of an individual patient. Using a set of a priori criteria, we systematically searched Medline and EMBASE databases for articles evaluating brain structure at the time of the first psychotic episode and assessed response to treatment, symptomatic outcome, or functional outcome at any point in the first 12 months of illness. The 11 studies identified suggest that alterations in medial temporal and prefrontal cortical areas, and in the networks that connect them with subcortical structures, are promising neuroanatomical markers of poor symptomatic and functional outcomes. Neuroimaging data, possibly in combination with other biomarkers of disease, could help stratifying patients with psychoses to generate patient clusters clinically meaningful, and useful to detect true therapeutic effects in clinical trials. Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE), a large multicenter study funded by the FP7 European Commission, could generate these much-needed findings.

The optimization of treatment and management of schizophrenia in Europe (OPTiMiSE) trial: rationale for its methodology and a review of the effectiveness of switching antipsychotics.

Most of the 13 542 trials contained in the Cochrane Schizophrenia Group's register just tested the general efficacy of pharmacological or psychosocial interventions. Studies on the subsequent treatment steps, which are essential to guide clinicians, are largely missing. This knowledge gap leaves important questions unanswered. For example, when a first antipsychotic failed, is switching to another drug effective? And when should we use clozapine? The aim of this article is to review the efficacy of switching antipsychotics in case of nonresponse. We also present the European Commission sponsored "Optimization of Treatment and Management of Schizophrenia in Europe" (OPTiMiSE) trial which aims to provide a treatment algorithm for patients with a first episode of schizophrenia. We searched Pubmed (October 29, 2014) for randomized controlled trials (RCTs) that examined switching the drug in nonresponders to another antipsychotic. We described important methodological choices of the OPTiMiSE trial. We found 10 RCTs on switching antipsychotic drugs. No trial was conclusive and none was concerned with first-episode schizophrenia. In OPTiMiSE, 500 first episode patients are treated with amisulpride for 4 weeks, followed by a 6-week double-blind RCT comparing continuation of amisulpride with switching to olanzapine and ultimately a 12-week clozapine treatment in nonremitters. A subsequent 1-year RCT validates psychosocial interventions to enhance adherence. Current literature fails to provide basic guidance for the pharmacological treatment of schizophrenia. The OPTiMiSE trial is expected to provide a basis for clinical guidelines to treat patients with a first episode of schizophrenia.

Regulatory science in Europe: the case of schizophrenia trials

In April, 2013, new guidance for phase 3 clinical trials in patients with schizophrenia came into effect.1 The guidance, issued by the European Medicines Agency (EMA),2 is intended to guide the design of regulatory studies of new antipsychotic drugs requiring a marketing authorisation for schizophrenia in Europe. Here, we report some aspects of this official document that could negatively affect assessment of drugs for schizophrenia, together with some possible solutions. Schizophrenia is a particularly challenging area, because several active treatments are already available, placebo response is high, and treatment response can be erratic and variable.

Psychiatrists' perceptions of the clinical importance, assessment and management of patient functioning in schizophrenia in Europe, the Middle East and Africa.

BackgroundIt has been estimated that as many as two thirds of patients with schizophrenia are unable to perform basic personal and social roles or activities. Occupational functioning and social functioning, as well as independent living, are considered as core domains of patient functioning. Improvement in patient functioning has also been recognized as an important treatment goal in guidelines and an important outcome by regulatory agencies. Nevertheless, information is lacking on how these aspects are being considered by psychiatrists across the world and how they are being assessed and managed.MethodsThe ‘Europe, the Middle East and Africa functioning survey’ was designed to canvas opinions of psychiatrists across these regions to ascertain their perceptions of the clinical importance, assessment and management of functioning amongst their patients with schizophrenia. The survey comprised 17 questions and was conducted from March to April 2011 in 42 countries. Data collected included the demographics of respondents and their opinions regarding personal and social functioning in patients with schizophrenia.ResultsResults were obtained from 4,163 clinicians. Psychiatrists estimated that more than two thirds (70%) of their patients with schizophrenia showed impaired or very poor levels of functioning. The majority of psychiatrists (92%) believed that personal and social functioning was an important treatment goal for patients with schizophrenia, and 91% believed it was an important goal for patients’ families. The majority of psychiatrists (55%) assess the personal and social functioning of their patient at each visit; however, 81% reported that they determine the level of functioning through clinical interview and not by using a specific assessment scale. To manage personal and social functioning in their patients, 26% of psychiatrists prefer pharmacological interventions, whereas 46% prefer psychosocial interventions.ConclusionPsychiatrists recognize that functioning is impaired/very poor in patients with schizophrenia, and there is still an important need to address functioning as a main treatment goal for patients with schizophrenia.