Comparison of the effects of quetiapine extended-release and quetiapine immediate-release on cognitive performance, sedation and patient satisfaction in patients with schizophrenia: a randomised, double-blind, crossover study (eXtRa).

OBJECTIVES: To assess daytime cognitive performance, sedation and treatment satisfaction in patients with schizophrenia receiving quetiapine extended release (XR) versus quetiapine immediate release (IR). METHODS: Phase IV prospective, double-blind, crossover study (NCT01213836). Patients (N=66) with stable schizophrenia, treated with XR or IR before study start, were randomised (1:1) to treatment with XR followed by IR, or IR followed by XR, at the dose received before enrolment (400-750mg). After 10-16days on formulation 1, patients switched to formulation 2. Assessments from three post-dose visits (≥5days following treatment on each formulation) were analysed. Cognitive performance was measured by CogState Cognition testing. Sedation, treatment satisfaction and safety were also assessed. RESULTS: 65 patients received treatment (69.2% male; mean age 37.8years). Daytime cognitive functioning was similar for both groups; adjusted mean difference in Attentional Composite Score in XR and IR patients was 0.005 (p=0.907). Patients receiving XR were less sedated than those receiving IR, (Bond-Lader visual analogue scale score, mean [SD]: 23.5 [19.0] vs 28.6 [21.4]); estimated overall treatment difference: 5.2 (95% CI: 2.3, 8.2; p<0.0009). Patients receiving XR reported feeling less sedated than those on IR (Stanford Sleepiness Scale, mean [SD]: 2.4 [0.9] vs 2.6 [1.0]); estimated overall treatment difference: 0.28 (95% CI: 0.12, 0.43; p<0.0008). Patients reported improved overall treatment satisfaction (p=0.0417) and milder side effects (p=0.0035) with XR. Safety profile was similar in both groups. CONCLUSION: Daytime cognitive performance was similar for both groups. XR was associated with less daytime sedation and improved patient satisfaction than IR.

First-episode psychosis and migration in Italy (PEP-Ita migration): a study in the Italian mental health services.

BACKGROUND: It has been frequently reported a higher incidence of psychotic disorders in immigrants than in native populations. There is, however, a lack of knowledge about risk factors which may explain this phenomenon. A better understanding of the causes of psychosis among first-generation migrants is highly needed, particularly in Italy, a country with a recent massive migration. METHODS/DESIGN: The "Italian study on first-episode psychosis and migration (PEP-Ita)" is a prospective observational study over a two-year period (1 January 2012-31 December 2013) which will be carried out in 11 Italian mental health centres. All participating centres will collect data about all new cases of migrants with first-episode psychosis. The general purpose ("core") of the PEP-Ita study is to explore the socio-demographic and clinical characteristics, and the pathways to care of a population of first-episode psychosis migrants in Italy. Secondary aims of the study will be: 1) to understand risk and protective factors for the development of psychotic disorders in migrants; 2) to evaluate the correlations between psychopathology of psychotic disorders in migrants and socio-demographic characteristics, migration history, life experiences; 3) to evaluate the clinical and social outcomes of first-episode psychoses in migrants. DISCUSSION: The results of the PEP-Ita study will allow a better understanding of risk factors for psychosis in first-generation migrants in Italy. Moreover, our results will contribute to the development of prevention programmes for psychosis and to the improvement of early intervention treatments for the migrant population in Italy.

Thirty-five years of community psychiatry in Italy.

The Italian Psychiatric Reform of 1978 is reviewed here in terms of national/regional mental health (MH) policies and with the help of epidemiological data. The reform law was essentially a framework one, and Italy's 21 regions were called to draft detailed organizational norms and to implement their systems. This explains a relevant interregional variability, despite several national MH plans. In a recent survey, compliance with national standards found homogeneous implementation on structural parameters but quite a variable one on functional parameters (continuity, coordination, accessibility, specialization). Epidemiological data show the impact of regional variability on the quality of treatment provided. Because of discrepancies among regional information systems, we analyze data from six Italian regions, where regional case registers have long been implemented, focusing on adult population prevalence and incidence rates and outpatient-inpatient care. Indicators of service use and some national MH documents are discussed in relation to the system's future prospects.

Primary care psychiatry in Italy.

In Italy, the importance of integrating primary care and mental health has only recently been grasped. Several reasons may explain this delay: a) until 2005, primary care physicians worked individually instead of in group practices, without any functional network or structured contacts with colleagues; b) community mental health centers with multiprofessional teams were well structured and widespread in several regions but focused on people with severe and persistent mental disorders; and c) specific national government health policies were lacking. Only two regions have implemented explicit policies on this issue. The "G. Leggieri" program started by the Emilia-Romagna region health government in 1999 aims to coordinate unsolicited bottom-up cooperation initiatives developing since the 1980s. In Liguria, a regional work group was established in 2010 to boost the strategic role of collaborative programs between primary care and mental health services. This article describes the most innovative experiences relating to primary care psychiatry in Italy.

Unmet needs and research challenges for late-life mood disorders.

Mood disorders are common and often under-recognised in older people whereby, together with the general ageing of the population, they are becoming a significant and growing public health problem worldwide. However, the need to address the problem of late life mood disorders in a real-world setting is met with a surprising lack of strong evidence in this field. Randomised clinical trials which focus on elderly mood disorders are not very common and the majority of them focus on pharmacological treatment of major depression. The aim of this study was to review first the main unmet needs and research challenges in late-life mood disorders as a basis to then review the state of the art evidence resulting from randomised clinical trials and the main critical aspects of their implementation. Comorbidity as well as polypharmacy, cognitive decline, unpredictable placebo response, and uncertainty on optimal duration of trials are some of the challenges the investigator has to address. Moreover, some methodological limitations of randomised clinical trials reduce the applicability of the results of such studies to common clinical practices and have encouraged some authors to investigate the existence of possible alternative research designs such as pragmatic randomised clinical trials.

The potential protective effect of tramiprosate (homotaurine) against Alzheimer's disease: a review.

Due to the progressive aging of the population and to the age-associated increase in its incidence, Alzheimer's disease (AD) will become in near future one of the major challenges that healthcare systems will have to face with in developed countries. Since the pathophysiological process of AD is thought to begin many years before the clinical diagnosis of dementia, in theory there is an opportunity for preventive therapeutic interventions. In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies, in the beneficial effects of some natural compounds in preventing various age-related pathologic conditions, including brain aging and neurodegeneration. Homotaurine, a small aminosulfonate compound that is present in different species of marine red algae, has been shown, in both in vitro and in vivo models, to provide a relevant neuroprotective effect by its specific anti- amyloid activity and by its γ-aminobutyric acid type A receptor affinity. The therapeutic efficacy of homotaurine in AD has been investigated in a pivotal Phase III clinical study that did not reach its pre-defined primary endpoints. However, post-hoc analyses have shown positive and significant effects of homotaurine on secondary endpoints and subgroups of patients, including a reduction in hippocampal volume loss and lower decline in memory function in the overall cohort, as well as a reduction in global cognitive decline in APOE4 allele carriers, suggesting a disease-modifying effects. In this review, we will examine the pre-clinical and clinical evidence supporting the potential role of homotaurine as a promising candidate for both primary and secondary prevention of AD.

Rethinking the role of long-acting atypical antipsychotics in the community setting.

Schizophrenia is a relapsing and evolving condition, which requires treatment continuity. Increasing evidence shows that antipsychotic discontinuation is associated with relapse in most patients, and that early interventions have a positive impact on long-term outcomes. Poor adherence to antipsychotics is a major factor in the treatment of schizophrenia and a relevant risk factor for relapse. Considerable effort has been made toward improving adherence, including the development of long-acting injectable (LAI) antipsychotics. LAIs have traditionally been reserved for patients with repeated nonadherence; currently, several misconceptions prevent their more widespread use. The recent introduction of LAI formulations of atypical antipsychotics and the encouraging results in terms of the reduction in relapse rates and avoidance of hospitalization warrant a reassessment of the role of LAIs in the management of schizophrenia. This paper presents the position of a panel of nine Italian schizophrenia experts on the use of novel LAI medications, with a focus on community-based services, the prevailing setting of schizophrenia treatment in Italy. The need to change the attitude toward LAIs--no longer a treatment of last resort, but a component of multimodal strategies leading patients to remission and rehabilitation--is emphasized. The paper also presents recommendations for LAI atypical antipsychotic use in the community setting.

Process of implementation and development of early psychosis clinical services in Italy: a survey.

AIM: To carry out an in-depth survey into the method of providing early intervention in schizophrenia in Italy and to evaluate the process of development of early psychosis clinical services following the pilot programme 'Programma 2000' and the publishing of Italian National Guidelines. METHODS: Topic-specific national and international clinical and research programmes, alongside national guidelines, were taken into consideration in order to create an ad hoc questionnaire. A telephone survey using this questionnaire was carried out. A randomized sample of 152 mental health centres (MHCs) were involved, equal to 21.5% of all Italian MHCs. RESULTS: The process of nationwide diffusion of early psychosis clinical services in Italy is frustratingly slow. Italian MHCs, including a specialized service for early interventions in schizophrenia, are estimated at being between 20% and 30%. Most services adopt a generalist approach and more frequently follow guidelines drawn up within the centres than Italian National Guidelines, involve few patients and provide a high variability of treatment options. The distribution of these services in Italy is not homogenous and influenced by demographic factors. CONCLUSION: Our data are consistent with worldwide literature showing a slow and variable implementation of early psychosis services in all nations. The main efforts to make these services diffused should be addressed to favour the process of localized adaptation to the guidelines, to demand possible and realistic implementation of the standard method, to stimulate policy endorsement and resources' allocation, and to particularly support the rural and the poorer zones.

Individuals, social changes and psychiatric services: continuity and innovation.

Over the last few years, psychiatry has had to deal more in depth with the mutation of social frames and of problems expressed by the community, which has changed itself, in particular at a cultural level. The historical attitude of psychiatry, which is to combine a scientific approach with recognizing the rights of all individuals involved in the healing system, can be very helpful in keeping services in touch with the new needs of society and places the neurosciences in a peculiar position.

Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia.

BACKGROUND: One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study. METHODS/DESIGN: The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome. DISCUSSION: The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.