Implementation of early intervention clinical services within the National Health System in Italy: Third wave survey with focus on structures, resources, and fidelity to the evidence-based model.

BACKGROUND: Early intervention in psychosis (EIP) is a well-established approach aimed at detecting and treating early signs and symptoms of psychosis to prevent its long-term consequences. The present study aimed at detailing the current status of EIP services in Italy, covering all the Departments of Mental Health (DMHs) operating in 2018. METHODS: All directors of public DMHs operating in Italy in 2018 (n = 127) were invited to fill in a Census form about EIP structure and activities. The first episode psychosis services fidelity scale (FEPS-FS) was used to investigate fidelity to the EIP model of the centre. RESULTS: An active EIP service was reported by 41 DMHs (32% of the total DMHs; 56% of those who took part in the survey). Most EIP services had an autonomous team. The large majority of the Italian EIP centres provided psychosocial interventions to their patients, principally psychotherapy, family support, and psychoeducation. Among those with an active EIP, 29 DMHs filled in the FEPS-FS. Internal consistency was good when based on the replies of the respondents, but reliability was weak when measured on the basis of an independent evaluation (Cohen's kappa = 0.571). The fidelity to the guidelines for early intervention was uneven, with some criteria met by most centres, especially those peculiar to the Italian community psychiatry. CONCLUSION: A further spreading of the early intervention model across the Italian DMHs was found. A lack of resources might limit the use of specific psychosocial treatments, such as cognitive-behavioural therapy or manualized family support.

Antipsychotics are related to psychometric conversion to psychosis in ultra-high-risk youth.

BACKGROUND: The prescription of antipsychotics outside overt psychotic conditions remains controversial, especially in youth where it is relatively widespread. Furthermore, some studies seem to indicate that antipsychotic exposure in individuals at ultra-high-risk (UHR) for psychosis is associated with higher conversion rates. This study was set up to test whether the inter-current prescription of antipsychotics in UHR patients was related to the psychometric threshold for a diagnosis of psychosis. METHODS: The 24-item Brief Psychiatric Rating Scale (BPRS) was used to quantify treatment response up to 2 years in 125 UHR participants. Standard psychometric criteria were used to quantify conversion to psychosis. Kaplan-Mayer and Cox proportional hazard survival analysis were applied to determine the impact of having or not received the prescription of an antipsychotic drug. RESULTS: Over the study period 30 (24%) subjects received the prescription of an antipsychotic. In the sample, there were 31 participants (25%) who had reached the psychometric threshold for conversion to psychosis after 2 years of treatment. UHR people who received a prescription of antipsychotics during the first 2 years of treatment were statistically more likely to reach the psychometric threshold for conversion to psychosis on the BPRS: Hazard ratio = 3.03 (95%CI: 1.49-6.16); p = .003. CONCLUSION: This finding supports the hypothesis that the prescription of antipsychotics within UHR cohorts is to be considered a red flag for higher incipient risk of conversion to psychosis.

Time-course of clinical symptoms in young people at ultra-high risk for transition to psychosis.

BACKGROUND: Ultra-high risk (UHR) people are a heterogeneous group with variable outcomes. This study aimed at (a) estimating trajectories of response to treatment to identify homogeneous subgroups; (b) establishing the impact on these trajectories of known predictors of outcome in UHR subjects. METHODS: Mixed models of growth curves and latent class growth analysis (LCGA) were applied to the 24-item brief psychiatric rating scale (BPRS) to measure the response to treatment over 2 years in 125 UHR participants. Group differences were tested on sociodemographic variables and clinical indicators that are known to affect the outcome in UHR people. RESULTS: BPRS scores decreased across all tested models, with a greater decrease for affective and positive symptoms than for all other dimensions of BPRS. Past admissions to the hospital for psychiatric reasons other than psychosis and the presence of a decline in premorbid functioning before the episode were associated with a slower decrease of BPRS score. LCGA identified three classes, one (82% of participants) with a progressive decrease in the BPRS scores, a second class with a moderate improvement (10%), and a third with no improvement (8%). Those in the 'no improvement' class had a higher chance of receiving a diagnosis of psychosis within the spectrum of schizophrenia. CONCLUSION: Most UHR individuals that are treated within a specialized service undergo substantial improvement in their psychopathology, but some seem resistant to the protocol of treatment and need close reevaluation within the first 12 months of treatment.

Through the prism of comorbidity: A strategic rethinking of early intervention in obsessive-compulsive disorder.

The diagnostic criteria for obsessive-compulsive disorder (OCD) have undergone minor changes in DSM-5 yet a major turnaround intervened in the overarching categorical allocation. OCD indeed has been separated from the anxiety disorders and included in an autonomous class of OCD-related disorders. Converging factors, i.e., the specificity of the clinical phenotype, the robust evidence for familial aggregation, the availability of effective treatments, and the increasing awareness of the role of environmental factors in its onset and course make OCD a suited target for tailored early intervention programs. However, studies on the topic are still scarce and OCD remains marginally conceptualized within an overdue early detection/intervention framework. Starting from the consolidated clinical evidence of OCD extensive comorbidity with schizophrenia-spectrum and bipolar disorders, we articulate a strategic proposal for a more integral incorporation of OCD within early detection and intervention paradigm.

International application of standards for health care quality, access and evaluation of services for early intervention in psychotic disorders.

AIM: Standards for health care quality, access and evaluation of early intervention in psychosis services are required to assess implementation, provide accountability to service users and funders and support quality assurance. The aim of this article is to review the application of standards in Europe and North America. METHODS: Descriptive methods will be used to illustrate the organizational context in which standards are being applied and used, specific measures being applied and results so far. RESULTS: Both fidelity scales and quality indicators of health care are being used. Fidelity scales are being applied in Australia, Canada, Denmark, Italy and United States. In England, quality indicators derived from the National Institute for Health and Care Excellence guidance are being used. CONCLUSION: In the last 4 years, significant progress has been made in the development and application of measures that assess quality and access to evidence-based practices for early intervention in psychosis services. This represents an important step towards providing accountability, improving outcomes and service user experience. The methods used allow for comparison between the services that are assessed with the same methods, but there is a need to compare the different methods. Further research is also required to explore links between quality of care and outcomes for community mental health services that deliver early intervention in psychotic disorders.

Anxiety sensitivity dimensions in young individuals with at-risk-mental states.

Anxiety Sensitivity (AS) is a transdiagnostic risk factor involved in the development and maintenance of different psychopathological conditions including anxiety disorders and psychosis. It consists of Physical Concerns (e.g., the belief that palpitations lead to a cardiac arrest), Social Concerns (the belief that observable anxiety reactions will elicit social rejection), and Cognitive Concerns (the belief that cognitive difficulties lead to mental incapacitation). No study investigated whether specific AS dimensions are related to At-Risk Mental States (ARMS). This study compared AS dimensions between young individuals with ARMS, patients after a recently occurred First-Episode Psychosis (FEP) and matched community controls. Based on models of ARMS and previous evidence, it was hypothesized that ARMS individuals have higher physical, social and cognitive concerns than FEP patients and controls. Thirty individuals with ARMS and 30 with FEP and 30 controls recruited from the general population completed the Anxiety Sensitivity Index-3 (ASI-3) and Penn State Worry Questionnaire. ARMS and FEP individuals had higher scores than controls on ASI-3 Cognitive Concerns [F( 2,87)= 11.48, p<.001]. Individuals with ARMS had higher ASI-3 Physical Concerns scores than FEP patients [F( 2,87)= 5.10, p<.01] and at a marginal significance level than controls. No between-group difference was found on Social Concerns. Higher ASI-3 Physical Concerns scores [B = -.324, Wald's χ2 (1) = 8.29, p < .01] and psychiatric comorbidities [B = -2.726, Wald's χ2 (1) = 9.33, p < .01] were significantly related to ARMS than FEP. Higher ASI-3 Social Concerns scores were related to FEP, despite at a marginal significance level [B =.213, Wald's χ2 (1) = 3.79, p = .052]. Interventions for AS Cognitive/Physical Concerns could be incorporated in the treatment of ARMS. A replication of the findings is required. Future longitudinal studies should examine whether Cognitive Concerns predict development of FEP in ARMS to improve early detection and prevention strategies.

Outcome at 2-year of treatment in first-episode psychosis patients who were enrolled in a specialized early intervention program.

Treatment in early intervention services (EIS) seems superior to treatment as usual on several outcomes, but the extent of heterogeneity in response is unclear. In this study, treatment response trajectories up to 2 years in first-episode psychosis (FEP) patients enrolled in an Italian early intervention service (EIS) have been quantified. The 24-item Brief Psychiatric Rating Scale (BPRS) was used to quantify treatment response up to 2 years in 129 participants. Conditional growth modeling and latent class growth analysis were used to test changes over time in the BPRS and separation into independent classes over time. Group differences were tested on socio-demographic and clinical variables known to be related to outcome in psychosis. Scores on the BPRS showed a statistically significant decrease in overall scores across all tested models. Four trajectories were identified across 2 years. Most patients showed a progressive decrease in the BPRS scores; a scant fraction showed a more stepped decrease from very high levels of psychopathology. No potential predictor was statistically related to the time course of BPRS scores. Most patients that undergo treatment within an EIS are characterized by amelioration, but patients that have higher baseline scores of psychopathology require more intensive treatment.

Dimensional structure of first episode psychosis.

AIM: Current diagnostic systems, DSM-5 and ICD-10, still adopt a categorical approach to classify psychotic disorders. The present study was aimed at investigating the structure of psychotic symptomatology in both affective and non-affective psychosis from a dimensional approach. METHODS: Participants with a first episode psychosis (FEP) were recruited from a cluster-randomized controlled trial (GET-UP PIANO TRIAL), offered to all Community Mental Health Centres (CMHCs) located across two northern Italian regions. After clinical stabilization, patients were assessed with a comprehensive set of psychopathological measures including the Positive and Negative Syndrome Scale, the Hamilton Depression Rating Scale and the Bech-Rafaelsen Mania Rating Scale. A two-step cluster analysis was performed. RESULTS: Overall, 257 FEP patients (male, n = 171, 66.5%; mean age = 24.96 ± 4.56) were included in the study. The cluster analysis revealed a robust four-cluster solution: delusional-persecutory (n = 82; 31.9%), depressed (n = 95; 37%), excited (n = 26; 10.1%) and negative-disorganized (n = 54; 21%), thus suggesting a quadripartite structure with both affective and non-affective dimensions. Among non-affective dimensions, negative and disorganization symptoms constituted a unique construct apart from positive symptoms. CONCLUSIONS: Symptom dimensions may represent a useful tool for dissecting the indistinct and non-specific psychopathology of FEP in order to better target specific interventions.

Secondary school teachers and mental health competence: Italy-United Kingdom comparison.

AIM: The aim of this study was to evaluate the differences between teachers' knowledge about early psychosis among three different Italian cities and a UK sample. METHODS: The sample consisted of 556 secondary school teachers from three different cities in Italy (Milan, Rome and Lamezia Terme) and London (UK). The research was based on the Knowledge and Experience of Social Emotional Difficulties Among Young People Questionnaire. The Italian version of the questionnaire was used in Italy. RESULTS: Overall, 67.6% of English teachers, 58.5% of Milan's teachers, 41.8% of Rome's teachers and 33.3% of Lamezia Terme's teachers were able to recognize psychotic symptoms from a case vignette. Logistic regression analysis showed that 'city' was the only independent variable significantly related to the correct/wrong answer about diagnosis. CONCLUSIONS: We found statistically significant differences between the three Italian samples and the UK sample regarding teachers' knowledge about first signs of psychosis. English teachers showed a better knowledge than Italian teachers in general. Teachers from Milan, where a specific early detection program was established in 2000, seemed to be more familiar with early signs of psychosis than teachers in the other two Italian towns.

Implementation and development of early intervention in psychosis services in Italy: a national survey promoted by the Associazione Italiana Interventi Precoci nelle Psicosi.

AIM: This is the first comprehensive, nationwide survey aimed at collecting evidence about the process of implementation and development of early intervention in psychosis (EIP) services (EIPs) in Italy, following the establishment of the pilot program 'Programma 2000' in 1999 and the publishing of the Italian National Guidelines in 2007. This survey covers all the Departments of Mental Health (DMHs) operating in Italy in 2013. METHODS: Using a purpose-designed form to assess EIP implementation, all directors of public mental health services for adults throughout Italy (n = 216) were asked to provide information about the activities of EIP-relevant local services. The initial delivery was followed by a request for a prompt response. RESULTS: Out of 216 enquired DMHs, 103 provided computable answers to the survey (response rate = 48%). Among responders, 45 (44%) reported the implementation of EIP (one out of five DMHs operating in Italy). About a half of the active EIPs also targeted patients at ultra-high risk of psychosis (n = 27). Strict application of guidelines related to drug prescription was reported in 35% of EIPs. Conversely, 90% provided some kind of structured psychotherapy and psychoeducation. Among EIPs, a minority reported willingness to provide initial assessment/contact at the patient's home. CONCLUSION: Albeit slowly, the implementation of EIP is spreading throughout the Italian public network of mental health. There is still a wide variability in the distribution of EIP services across the Italian territory. Further efforts are necessary to stimulate policy endorsement and resource allocation, as well as to support the poorest zones.

Predictors and moderators of treatment outcome in patients receiving multi-element psychosocial intervention for early psychosis: results from the GET UP pragmatic cluster randomised controlled trial.

BackgroundThe GET UP multi-element psychosocial intervention proved to be superior to treatment as usual in improving outcomes in patients with first-episode psychosis (FEP). However, to guide treatment decisions, information on which patients may benefit more from the intervention is warranted.AimsTo identify patients' characteristics associated with (a) a better treatment response regardless of treatment type (non-specific predictors), and (b) a better response to the specific treatment provided (moderators).MethodSome demographic and clinical variables were selected a priori as potential predictors/moderators of outcomes at 9 months. Outcomes were analysed in mixed-effects random regression models. (Trial registration: ClinicalTrials.gov, NCT01436331)ResultsAnalyses were performed on 444 patients. Education, duration of untreated psychosis, premorbid adjustment and insight predicted outcomes regardless of treatment. Only age at first contact with the services proved to be a moderator of treatment outcome (patients aged ⩾35 years had greater improvement in psychopathology), thus suggesting that the intervention is beneficial to a broad array of patients with FEP.ConclusionsExcept for patients aged over 35 years, no specific subgroups benefit more from the multi-element psychosocial intervention, suggesting that this intervention should be recommended to all those with FEP seeking treatment in mental health services.

Attitudes of Mental Health Workers Towards Early Interventions in Psychiatry: A National Survey.

Early intervention (EI) is an effective strategy to improve outcomes of psychiatric disorders, but there is little evidence on mental health professionals' opinions on this approach. Hence, during conferences on this topic, we surveyed participants on the benefits, aims, and barriers to implementation of EI. Participants reported that the most important outcomes of EI were decreasing the risk of long-term social consequences, of severe psychopathological conditions, and chronicization. EI would primarily need to be implemented in the care of psychotic, eating, and mood disorders, whereas the main barriers to EI implementation were the lack of funding and of a prevention-oriented culture. Although these results might be biased by a generic attitude favoring EI, participants showed a very positive attitude towards EI and stated the need of a culture shift towards a more prevention-oriented model in a mental health setting.

Feasibility and Effectiveness of a Multi-Element Psychosocial Intervention for First-Episode Psychosis: Results From the Cluster-Randomized Controlled GET UP PIANO Trial in a Catchment Area of 10 Million Inhabitants.

Integrated multi-element psychosocial interventions have been suggested to improve the outcomes of first-episode psychosis (FEP) patients, but they have been studied primarily in experimental settings and in nonepidemiologically representative samples. Thus, we performed a cluster-randomized controlled trial, comparing an integrated multi-element psychosocial intervention, comprising cognitive behavioral therapy, family intervention, and case management, with treatment as usual (TAU) for FEP patients in 117 community mental health centers (CMHCs) in a large area of northern Italy (10 million inhabitants). The randomized units (clusters) were the CMHCs, and the units of observation the patients (and, when available, their family members). The primary hypotheses were that add-on multicomponent intervention: (1) results in greater improvements in symptoms, as assessed with positive and negative syndrome scale and (2) reduces in-hospital stay, based on days of hospitalization over the 9-month follow-up. Four hundred and forty-four FEP patients received the intervention or TAU and were assessed at baseline and 9 months. Based on the retention rates of patients (and families) in the experimental arm, multi-element psychosocial interventions can be implemented in routine mental health services. Regarding primary outcomes, patients in the experimental arm showed greater reductions in overall symptom severity, while no difference could be found for days of hospitalization. Among the secondary outcomes, greater improvements were detected in the experimental arm for global functioning, emotional well-being, and subjective burden of delusions. No difference could be found for service disengagement and subjective burden of auditory hallucinations. These findings support feasibility and effectiveness of early interventions for psychosis in generalist mental health services.

Early intervention in psychosis: a feasibility study financed by the Italian Center on Control of Maladies.

AIM: In November 2005 the Italian Center on Control of Maladies, a department operating under the Ministry of Health, financed a project aimed at evaluating the feasibility of a protocol of intervention based on the early intervention in psychosis (EIP) model within the Italian public mental health-care network. METHODS: The study was carried out between March 2007 and December 2009. It involved five centres operating under the Departments of Mental Health of Milan (Programma 2000), Rome (area D), Grosseto, Salerno (Nocera) and Catanzaro (Soverato). RESULTS: Enrolment lasted 12 months, at the end of which 43 patients were enrolled as first-episode psychosis (FEP), and 24 subjects as ultra high-risk (UHR) patients. Both FEP and UHR samples included a preponderance of male patients. A family history of psychosis was rarely reported in both samples. The FEP incidence rate was lower than expected on the basis of international estimates of the incidence of schizophrenia but within the expected figure for the estimated Italian rates in three centres out of five. CONCLUSIONS: Overall, the study proved that an EIP centre can be established within the public Department of Mental Health to reach a good fraction of the cases in need of treatment. Since then, several studies have been set up to assess the feasibility of EIP in the Italian public mental health sector in Lombardy and Tuscany, and in 2012 the Emilia-Romagna Regional Authority started an educational plan aimed at implementing the EIP model in all the Mental Health Departments in the region.

Shades of vulnerability: latent structures of clinical caseness in prodromal and early phases of schizophrenia.

The underlying structures of clinical caseness and need of care in prodromal (i.e., at-risk) and early phases of schizophrenia remain poorly characterized in their essential psycho-behavioral coherence. To identify the schizophrenia proneness-related subtypes within a population of young help-seekers referred to a dedicated, community-based early detection program (Programma 2000). A sample of consecutive referrals (n = 168) for suspected psychosis or first-episode schizophrenia spectrum psychosis received a detailed clinical assessment, including the early recognition inventory for the retrospective assessment of the onset of schizophrenia checklist. We used exploratory factor analysis (EFA) to determine the underlying dimensional structure and latent class analysis (LCA) to identify putative vulnerability subtypes. EFA identified four factors: dysphoria (irritability tension), paranoid autocentrism, introversive withdrawal, and disturbed subjective experience. LCA distinguished three classes, interpretable as carrying different degrees of "proneness to schizophrenia psychosis," which best captured the underlying continuum of clinical severity. The validity of the three classes was supported by distinct patterns of association with major clinical variables (i.e., diagnostic staging at referral). Vulnerability to schizophrenia psychosis in young help-seekers may manifest in three major clinical prototypes, presenting common levels of dysphoria and social withdrawal but different degrees of paranoid autocentrism and disturbed subjective experience. Overall, the results provide the empirical background to dissect shared features of clinical caseness from more schizophrenia-specific vulnerability components. This is of value for the refinement of the clinical staging model as well as for the pragmatic implementation of multiple-gate screening programs.

Sex differences in first-episode psychosis and in people at ultra-high risk.

Sex-related differences in the clinical expression and outcome of schizophrenia have long been recognized; this study set out to evaluate whether they extend to those subjects who are at high risk of developing psychosis. In a sample enrolled in two early intervention programs in northern Italy, patients with first-episode psychosis (FEP; n=152) were compared to patients at ultra-high risk of psychosis (UHR; n=106) on a series of sex-related clinical characteristics of schizophrenia. In both the FEP and the UHR samples, males outnumbered females. In FEP patients, women had been referred at an older age than men and had a shorter duration of untreated illness (DUI) and of untreated psychosis. In UHR patients no sex differences were found in age of onset or DUI. There was no diagnosis by sex interaction on symptoms severity or level of functioning at presentation. The limited number of women in both samples, and the exclusion of people who were older than 30 and of those with substance dependence may have reduced the extent of sex-related differences in this study. Sex differences of precipitating factors for psychosis might be worthy of further investigation.

Patterns of referral in first-episode schizophrenia and ultra high-risk individuals: results from an early intervention program in Italy.

PURPOSE: This study set out to investigate the patterns of referral in a sample (n = 206) of patients having first-time access to an Italian comprehensive program that targets the early detection of and early intervention on subjects at the onset of psychosis. The primary goal of the study was to investigate the duration of untreated illness (DUI) and/or the duration of untreated psychosis (DUP) in the sample since the implementation of the program. METHOD: Data on pathways of referrals prospectively collected over a 11-year period, from 1999 to 2010; data referred to patients from a defined catchment area, and who met ICD-10 criteria for a first episode of a psychotic disorder (FEP) or were classified to be at ultra-high risk of psychosis (UHR) according to the criteria developed by the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne. Changes over time in the DUI and DUP were investigated in the sample. RESULTS: Referrals increased over time, with 20 subjects enrolled per year in the latter years of the study. A large majority of patients contacted a public or private mental health care professional along their pathway to treatment, occurring more often in FEP than in UHR patients. FEP patients who had contact with a non-psychiatric health care professional had a longer DUP. Over time, DUP and DUI did not change in FEP patients, but DUI increased, on average, in UHR patients. CONCLUSIONS: The establishment of an EIP in a large metropolitan area led to an increase of referrals from people and agencies that are not directly involved in the mental health care system; over time, there was an increase in the number of patients with longer DUI and DUP than those who normally apply for psychiatric services.

Patients With First-Episode Psychosis are Not a Homogeneous Population: Implications for Treatment.

OBJECTIVE: This study aimed at defining the characteristics of a population of patients diagnosed with first-episode psychosis (FEP), and accessing for the first time a center for early intervention in psychosis in the health district of Milan and its surroundings. METHODS: Patients were included in the study from January 2007 to December 2008; criteria: first contact with any public mental health service of the catchment area for a first episode of schizophrenia or related syndromes according to the ICD-10 criteria. Cluster analysis was used to divide patients into groups based on the main socio-demographic and clinical characteristics at presentation. RESULTS: Overall, 91 FEP patients were enrolled in the study. Two clusters were identified, which differed principally by symptom profile. Patients in cluster 1 (n=36) had severe agitation, and a history of alcohol and/or substance abuse at presentation more often than those in cluster 2 (n=55), who were more likely to suffer at presentation from severe depression or apathy, anxiety, poor self-care, functional or work impairment and severe social withdrawal. After six months of treatment patients improved on almost all symptomatic dimensions on the Health of the Nation Outcome Scale and the Brief Psychiatric Rating Scale, with greater improvement in cluster 1 than in cluster 2. CONCLUSIONS: The findings of this study need replication in larger samples and on a wider severity scale. Nevertheless, the heterogeneity of patients with FEP might impact on treatment. Policymakers should recognize the importance of the diagnostic and outcome assessment in the treatment of severe mental disorders.

Obstetric complications in early psychosis: relation with family history of psychosis.

The people classified as being at ultra-high risk (UHR) of developing psychosis are expected to share many risk factors for psychosis with the patients diagnosed with schizophrenia, including an enhanced incidence of obstetric complications (OCs). This study set out to investigate the incidence and correlates of OCs in a sample of patients accessing an early intervention center. Patients' mothers were asked whether they had suffered from any somatic complication during pregnancy from a list of OCs with potential direct relevance to the physical wellbeing of the offspring. Out of 86 patients diagnosed with first-episode psychosis, 20 (23%) cases were positive for the occurrence of severe OCs, as reported by their mothers during an interview; out of 83 UHR patients, 21 (25%) cases were positive for OCs. OCs were more common in individuals with a family history of psychosis than in those without such a history. OCs might interact with genetic vulnerability to increase the risk of psychosis. Lack of comparison to healthy controls is a limitation that decreases the value of these findings.

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial.

BACKGROUND: Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services. METHODS/DESIGN: The Psychosis early Intervention and Assessment of Needs and Outcome (PIANO) trial is part of a larger research program (Genetics, Endophenotypes and Treatment: Understanding early Psychosis - GET UP) which aims to compare, at 9 months, the effectiveness of a multi-component psychosocial intervention versus treatment as usual (TAU) in a large epidemiologically based cohort of patients with FEP and their family members recruited from all public community mental health centers (CMHCs) located in two entire regions of Italy (Veneto and Emilia Romagna), and in the cities of Florence, Milan and Bolzano. The GET UP PIANO trial has a pragmatic cluster randomized controlled design. The randomized units (clusters) are the CMHCs, and the units of observation are the centers' patients and their family members. Patients in the experimental group will receive TAU plus: 1) cognitive behavioral therapy sessions, 2) psycho-educational sessions for family members, and 3) case management. Patient enrollment will take place over a 1-year period. Several psychopathological, psychological, functioning, and service use variables will be assessed at baseline and follow-up. The primary outcomes are: 1) change from baseline to follow-up in positive and negative symptoms' severity and subjective appraisal; 2) relapse occurrences between baseline and follow-up, that is, episodes resulting in admission and/or any case-note records of re-emergence of positive psychotic symptoms. The expected number of recruited patients is about 400, and that of relatives about 300. Owing to the implementation of the intervention at the CMHC level, the blinding of patients, clinicians, and raters is not possible, but every effort will be made to preserve the independency of the raters. We expect that this study will generate evidence on the best treatments for FEP, and will identify barriers that may hinder its feasibility in 'real-world' clinical settings, patient/family conditions that may render this intervention ineffective or inappropriate, and clinical, psychological, environmental, and service organization predictors of treatment effectiveness, compliance, and service satisfaction.