Despite low prevalence rates, schizophrenia is considered among the most severe mental disorders, ranking among the leading causes of disability worldwide (1, 2). Clinically, patients living with schizophrenia (PLWS) experience psychotic, negative, disorganizative symptoms and cognitive impairments, the latter representing the most detrimental factors associated to functional decline (1, 3). Being characterized by a debilitating, multi-episodic and chronic progression in up to 60% of cases (4), schizophrenia is associated with massive social and economic costs for patients, caregivers, society and Mental Health Services (MHS). Indeed, in Italy in 2022, more than a third of psychiatric outpatient services were dedicated to the care of patients with schizophrenia (5). Moreover, if in Europe in 2010 the total cost of psychotic disorders (including schizophrenia) was estimated at 93.9 billion Euros (6), in Italy the economic burden for schizophrenia was estimated at around €2.7 billion (7), with 50.5% (almost €1.39 billion) due to indirect costs and 49.5% to direct costs (almost €1.37 billion). The latter corresponded, respectively, to drugs therapies (accounting for 10% of direct costs) and to hospitalizations (accounting for 81% of direct costs, including residential and semi-residential facilities) (7). Indeed, in Italy, 13.800 patients with schizophrenia were hospitalized from 2009 to 2016, with an average of 2.98 hospitalizations per patient (8). Considering indirect costs, the loss of productivity is an essential topic, involving both personal and caregiver’s functioning: indeed, families members and caregivers lost, on average, 44.1 working days yearly in activities linked to the disorder (7), and this is responsible of severe family burdens and reduced quality of life for relatives and caregivers (9). Moreover, it has been found that, in Italy approximately 15.000 PLWS received some social security benefits yearly from 2009 to 2015, with an average annual expenditure of €160.1 million (8). Indeed, throughout the course of illness, negative symptoms, impairments of adaptive life skills and of cognitive performance are a leading source of disability and altered real-life functioning (3, 10, 11). Furthermore, PLWS are characterized by reduced life expectancy with a weighted average of 14.5 years of life lost (12) and increased mortality rates that are more than double than the general population (13, 14), due to suicides (15) and, mostly, to cardiovascular diseases (16). Moreover, incidence rates of a wide range of somatic disorders (including diabetes mellitus, metabolic syndrome, respiratory, autoimmune disease, infections, cancers) are significantly higher among PLWS than in the general population (17, 18). Consequently, physical health is a major concern in the care of individuals with schizophrenia. Indeed, several external (i.e., accessibility to health care and medication) and internal factors (i.e., self-esteem, negative and cognitive symptoms, alimentation, and substance misuse) are responsible for the scarce physical health of affected individuals (19). However, on one hand, if poor lifestyle habits (e.g., smoking, sub-optimal treatment of somatic disorders) and medications account for much of the increased mortality risk due to somatic diseases (20), on the other hand current evidence from genetic studies suggested that a common shared genetic risk for cardiovascular risk factors and psychotic disorders could explain the increased risk for cardiovascular disorders (20, 21). Among external factors, the role of medications, primary antipsychotic compounds (AP) (first generation antipsychotics, FGA; and second generation antipsychotics, SGA), is controversial: on the one hand, if it is well known that AP are linked to metabolic side effects (including dyslipidemia, hyperglycemia, obesity and overweight, diabetes mellitus, thyroid disorders, hyponatremia) (22), on the other hand highest cumulative mortality rates were observed among those patients with no AP exposure whereas taking AP medication, at adequate dosages, is associated with lower mortality due to somatic comorbidities (23, 24). Moreover, possible different AP administration routes (oral versus long-acting injection, LAI) are other factors that could influence mortality rates in schizophrenia, with second generation long-acting injection (SG-LAI) associated with the lowest cumulative mortality rate and an approximately a 30% lower risk of death compared with oral agents (25).

An important issue in the care of PLWS is the role of pharmacological interventions, namely AP drugs. Indeed, these agents are relatively effective in improving positive symptoms, such as auditory hallucinations and delusions, but not markedly effective on negative symptoms and cognitive impairments (26). Marcellusi and colleagues found that of the 212.739 individuals diagnosed with schizophrenia in 2014 in Italy, the majority (~86%) were treated with AP pharmacotherapy (7), suggesting that most of patients required long-term, or even lifetime, medications to control their symptoms (1, 26). The authors also found that APs were usually combined with other CNS drugs (polypharmacotherapy) in more than half of the cases (7), confirming that add-on therapies were frequently prescribed in PLWS (27, 28). However, oral AP polypharmacy has been extensively associated to non-adherence phenomenon, to reduced tolerability and increased adverse effects and higher costs for MHS (29, 30). Coherently, in the U.S. in 2005, it was found that the national rehospitalization costs related to antipsychotic non-adherence were, on average, $1479 million (31). Indeed, as relapses can worsen the course and outcomes of the disorder by reducing treatment response and producing severe personal and societal repercussions (11), relapse prevention is essential for the management of schizophrenia for which MHS have to offer plans to reduce those factors contributing to relapse, including drug discontinuation (11). Thus, an effective option is to use LAI that, compared to oral AP, seems to improve the compliance and reduce the risk of relapse and of new hospitalizations (32, 33). Moreover, the involvement of patients in shared decision-making on pharmacotherapy is essential to improve the subjective quality of care (11, 34, 35).

Nevertheless, caring for PLWS does not solely end in treating these patients pharmacologically to control the symptoms of the disorder and it cannot be reduced to economic and financial aspects only. Indeed, if AP remain an essential starting point to achieve and maintain symptomatic remission, an effective management also requires that pharmacotherapy is embedded and integrated within a framework of multidisciplinary psychosocial interventions (including cognitive remediation for cognitive impairments, psychological treatments for resistant positive symptoms, family and social support, psychoeducation for patients and families, social skill training, employment services to improve personal work abilities, money management counseling) that have to be delivered in the community-care setting to improve quality of life, satisfaction, well-being and to achieve recovery (1, 4, 11, 26). Among this framework, the network of care should also involve a wide range of professionals and agencies (including, in- and out-patient services, community care centers, self-help groups, family organizations, psychiatrists, psychologists, nurses, social workers, case managers, and general practitioners, GPs) and, obviously, the patient (11). Moreover, it is essential that a congruent care pathway will be built according to a lifespan perspective and, most of all, according to the different stages of the disorder: indeed, three crucial stages have been identified in the course of schizophrenia, that are the prodromal and early phases, the acute states of decompensation and the long-term phases (4, 35). Among these phases, especially in the long-term management of chronicity, the above-cited psychosocial interventions seem to play an essential role improving overall psychosocial functioning (11). Thus, according to the patient’s needs, the value of the treatment has to comprise a combination of symptom reduction, improved quality of life, better social functioning and subjective well-being, and optimal physical health (11), and this is possible if MHS will shared their actions in combination with social systems and with all the stakeholders (including caregivers, self-help groups, family organizations, expert patients and GPs) involved in the everyday life of PLWS (11, 35). However, the ideal path care for PLWS have to address several structural and clinical unmet needs that include the early recognition/intervention plans (to reduce the duration of untreated psychosis), the treatment of resistant symptoms (including negative, depressive and cognitive symptoms), the personalization of pharmacological treatments to maintain remission and reduce non-adherence (weighing the relation between effectiveness and side effects), the need to deal with somatic comorbidities and comorbid substance abuse, and finally, the suboptimal integration of pharmacological and psychosocial interventions and the poor collaboration among health and social care professionals (4, 11). All of these problems concerning the ideal path care of PLWS have already been highlighted in a recent Italian Delphi study showing that, despite a strong consensus on these main components of schizophrenia path care was achieved by the experts, a strong gap exists in the everyday clinical practice on the effective implementation of these themes (4). Detailly, important concerns were found on the dissemination of early prevention/intervention plans, on the lack of structured symptomatologic assessment to guide the personalization of care and of pharmacological treatments (including, switching or augmenting APs, side effects assessment), on the lack of definitive plans to improve treatment adherence, and to monitor cardiovascular/metabolic risk and on the management of somatic comorbidities and physical health (4). Considering these concerns and according to Galderisi et al., 2019 (4), we unfortunately have to observe that the road to organizing an optimal treatment path for PLWS is still long and twisted by several critical barriers that must necessarily be overcome if MHS want to design a definitive treatment plan (11). Indeed, despite recovery is achievable, only 13.5% of affected individuals (1/7 patients) met the defined criteria for a full recovery (36). Recovery is an essential conceptualization that allowed psychiatrists to change the paradigm in treating schizophrenia, moving from a symptom control-based approach to an approach based on two essential aspects: remission (defined as a reduction/absence of symptoms to the point that they do not interfere significantly with behaviors) and functional improvement (defined as the ability to function, socially and vocationally, in the community) (37). In other words, recovery is a journey aimed at achieving a meaningful life which translates through an improved quality of life, physical health, social integration, instrumental competence and self-agency, and independent living (11). However, the low rate of recovery detected among individual with schizophrenia gives the idea that MHS have necessarily to further improve the current model of care by promoting the implementation of integrated and personalized treatments to overcome the existing barriers and, ultimately, to improve the functional outcome of affected individuals (4).

Thus, we previously conduct a survey – co-designed by clinicians, expert patients and caregivers – with the aim to identify current unmet needs, gaps and limitations between current knowledges and clinical practice to help MHS to further organize an optimal journey for PLWS, throughout all the three phases of schizophrenia, with the ultimate goal to achieve recovery (35). This survey focused on the most populous Italian region, Lombardy (~9 million inhabitants), and analyzed the levels of importance and of implementation for several clinical actions/interventions or themes considered of significant importance by the panel of clinicians, patients’ and caregivers’ associations and expert patients (EXP patients). The survey examined three macro-areas corresponding to the three essential phases of the schizophrenia course, early detection and management, the acute phase management, and the long-term management/continuity of care. We found that, for the management of early phases, despite a great consensus on the actions to be implemented to treat young individuals was found, the degree of implementation in the real-life practice was only moderate-to-good. Considering the management of acute states of decompensation, strong consensus and a good level of implementation in clinical practice were found. Finally, considering the long-term management and the continuity of care, a strong consensus was found, but the level of everyday implementation was slightly moderately implemented. Overall, we observed that early phases and chronicity management have to be further implemented to improve the Patient Journey of PLWS (35).

Based on the results obtained at regional level, we aimed to extend the Patient Journey Project at national level to analyze the situation in Italian MHS and to understand the current areas of clinical intervention that are properly implemented and the areas that deserve more implementation to enhance the treatment plans for PLWS.

First, the scientific board (encompassing social researchers, psychologists and psychiatrists) was created to build the survey’s statements. The scientific board was as composed as we wanted to create a survey with a multidisciplinary approach, attentive to both clinicians’ and patients’ needs. This phase concerned a desk research design to review the existing Italian regulatory sources, guidelines and best practices on the management of mental frailties and schizophrenia (38–47). The scientific board identified three areas of interest: early detection and management, acute phase management, and long-term management/continuity of care, as they were considered the most significant areas in the ideal journey of PLWS. Then, according to the Italian regulatory sources, guidelines and best practices, the scientific board identified a list of possible statements and shared it with 8 representatives of 4 patients’ and caregivers’ associations (Coplotta, Diversamente, Anpis Puglia, Club Itaca Milano) and with 3 expert peer supporter patients (aka, ESP patients). ESP patients are patients diagnosed with schizophrenia according to the ongoing classification for mental disorders that are trained at the regional level through a dedicated class to be recognized as expert peer supporters. ESP patients and caregivers were included given their relevance to patient engagement and their empowerment in clinical and institutional settings (48). As we considered of strategic importance to include all the stakeholders involved in the ideal patient’s journey of PLWS, this phase of sharing was essential to reinforce our multidisciplinary approach to build the survey (49). To do so, a semi-structured one-on-one interview was conducted by one clinician and one social researcher with ESP patients and patients’ and caregivers’ associations, with the purpose of collecting real-life evidence and relating what had emerged from the guidelines and best practices with the unmet needs still present in the management of schizophrenia. From this interview, after a thorough validation process carried out by clinicians, ESP patients and caregivers, the scientific board codified the final sixty statements of the survey, focusing on peculiar themes and topics.

For early detection and management, we analyzed several themes including: services accessibility, continuity of care, multi-disciplinary evaluation of patients’ needs, rehabilitation, psychoeducational and psychotherapeutic interventions, and drug treatment’s safety and appropriateness. For acute phase management, we investigated the following topics: experience of hospitalization, prevention and decrease in commitment and forced treatment and physical restraints, and linkage to local and outpatient services. For long-term management/continuity of care, the topics were: individual treatment plans, psychoeducational interventions, continuity in drug treatment, patient’s physical health awareness, recovery and social integration interventions, social and job support, and residential and semi-residential interventions. The survey was deployed with the CAWI (computer-assisted web interviewing) method by using a web program created and developed to manage research, surveys and customer satisfaction studies. Finally, the survey comprised a 60-statements questionnaire built on the three main areas of interest, divided as follows (see, Table 1): 17 statements on the early detection and management, 16 statements on acute phase management, 27 statements on the long-term management/continuity of care. To answer the survey, the respondents had to express agreement or disagreement on a 5-point Likert scale. Each statement was analyzed according to 2 subscales. The first subscale assessed the importance of the statement, from (1) “of no importance” to (5) “extremely important”. The second subscale assessed the degree of implementation of the statement in the clinical practice, from (1) “not implemented at all” to (5) “extremely implemented”.

The survey was sent to Italian psychiatrists working as Heads of the Mental Health Departments and Addiction Services (MHDAS) or as facilities directors, regardless of whether they worked in academic or non-academic settings. No patients, caregivers or other stakeholders completed the survey.

Considering the study aims, the first purpose was to evaluate whether respondents could consider the selected statements to be of strategic importance according to their knowledge, best practice guidelines and national regulatory sources. This goal was achieved by analyzing the importance of the statement subscale. Subsequently, by analyzing the degree of implementation subscale, the survey aimed to evaluate whether the available knowledge and guidelines were currently implemented in clinical practice, according to the respondents’ judgment, and the possible gaps that exist between guidelines and clinical practice.

The results on the effective management of PLWS were analyzed considering a general overview of the responses, the assessment of the consensus level on the importance of the statement, the evaluation of the degree of implementation, the possible existing gaps between the guidelines and clinical practice.

Adopting only descriptive statistical analyses (mean scores, the mode and median values), the appropriate analyses were calculated using the IBM® SPSS Statistics Version 20 software. No a priori assumptions were made.

The interpretation of the results followed the same criteria that were applied in our previous publication (35) as follows:

For the interpretation of the results, we focused on the mean score values.

To strength our analyses, we also derived a difference (Δ) score by subtracting the mean values form the importance of the statement subscale to the degree of implementation subscale: when the Δ was bigger than 1, this meant that there was a large discrepancy between the importance attributed to the statement and the degree of implementation in the real-life context.

Respondents included 38 Heads of Mental Health Department and 22 facilities directors from all the Italian Regions, except for Basilicata, Friuli-Venezia Giulia, Sardinia and Veneto. Lombardy was the most represented Region (28.3% of the respondents), followed by Sicily and Campania (both, 13.3% of the respondents). More than half of the respondents (56.7%) worked in medium municipalities (10’000-100’000 inhabitants), 18.3% in medium-large municipalities (100’000-250’000 inhabitants), 15% in large municipalities (over 250’000 inhabitants) and 10% in small municipalities (under 10’000 inhabitants). No missing data was found, as all 60 respondents filled out all the statements.

The results on the importance of the statement and degree of implementation for the three macro-areas are summarized in Table 1 (mean score values) and in Table 2 (the mode and median values).

Considering results from the importance of the statement subscale, the fact that a strong consensus was reached for almost the statements suggests that Heads of MHDAS and facilities directors have clearly in mind that the management of the ideal Patient Journey for PLWS must involve all the phases of schizophrenia, from the early stages of detection and treatment up to the management of acute decompensation and, above all, to the management of chronicity. These results are congruent with National guidelines (46, 47) and international literature (11) suggesting that differential clinical actions should be organized according to the different clinical needs that PLWS could present throughout the course of their illness. Conversely, respondents reached a poor consensus on only one item in the long-term management/continuity of care area that examined the provision of psychotherapeutic treatment for family members. Moreover, this statement also showed a poor level of implementation. Although the family milieu has a central role in caring for PLWS with an increased emotional cost for caregivers (51), we found that family interventions are poorly implemented in clinical practice despite their strong scientific basis (52, 53).

These finding have important implications clinically: in fact, on the one hand they suggest the need to further raise awareness among Heads of MHDAS in promoting psychotherapeutic interventions for PLWS and for their families. Furthermore, since scientific evidence has found robust benefits for psychotherapeutic treatments (including, family interventions, family psychoeducation, and cognitive behavioral therapy) in preventing relapse (52) and reducing symptoms burden (53) both in the early phases (53) and in the long-term treatment (52), we recommend that national providers and legislators will provide specific plans to further implement these neglected interventions in clinical practice.

The survey also found that only a minority of the statements showed good levels of implementation. Particularly, 2/17 statements in the early detection and management, 3/16 statements in the acute phase management and 1/27 statement in the long-term management/continuity of care reached good levels of implementation. This was especially true for the statements that examined the role of pharmacological treatments throughout the course of schizophrenia. Indeed, it was found that respondents considered that the provision of an effective and well-tolerated antipsychotic treatment is among the few aspects already implemented in clinical practice. Indeed, for the early detection and management area, two statements presented good level of implementation (to provide adequate pharmacological treatments and to consider the safety and tolerability profiles of AP compounds): these results are in line with a recent Delphi study on the pattern of care for adolescents with schizophrenia, suggesting that SGA should be preferred to FGA as they are associated to better tolerability and safety profile (54). Moreover, this confirms that the idea that the choice of the AP compound by clinicians should be guided by the subjective characteristics of the affected individual (including, the symptomatic manifestations, the illness stage, the presence of medical comorbidities or concomitant substance abuse) and should be shared with the patient and the family (54). Similarly, in the acute phase management area, good levels of implementation were found on the statements that consider the provision of a safe and well-tolerated pharmacological treatment with the idea to start as soon as possible an AP prescription. Thus, given the documented efficacy of different AP during acute states of decompensation (55), it must be highlighted that clinicians should personalize AP prescription taking into consideration the balancing between the effectiveness of a given molecule and possible related side effects (56). Furthermore, as the milestone in treating of PLWS is to achieve functional recovery and better quality of life, it is not surprising that the survey found that, in the long-term management/continuity of care, the possibility to offer LAI treatment in case of frequent relapses and poor adherence was at good level of implementation. This confirm that clinicians considered LAI regimen an essential strategy to improve adherence and prevent the risk of relapse and of new hospitalizations (33, 33).

These findings have important clinical implications especially for what concerns the personalization of pharmacological treatments: what could guide the clinician in personalizing the treatment, through the process of shared decision-making (34), is a careful evaluation of the tolerability profile of the chosen molecule for example by taking into consideration the anticholinergic burden and the metabolic effects that characterize each antipsychotic compound.

On the other hand, the survey also to demonstrate that, among Italian MHS, some interventions had poor levels of implementation: in detail, in 1/17 statements of early detection and management and 4/27 statements on the long-term management/continuity of care, but none in the acute phase management. These results are somewhat encouraging as they reveal how the Italian Heads of MHDAS have been able to adequately implement most of the areas of intervention throughout the journey of PLWS. Nevertheless, it’s important to highlighted that, both in the early detection and long-term management, an issue that deserves further implementation is the effective involvement of GPs throughout the schizophrenia course, especially in preventive actions to detect individual in prodromal/early phases and in the management of chronicity evaluating patients’ lifestyle and physical health. As PLWS have more physical problems than the general population, GPs have an essential role in the management of mental and physical comorbidity as they often are the main entry point into the healthcare system (57). Moreover, GPs give support and information to the patient’s family (57). Thus, we recommend to further promote, through specific awareness campaigns, the collaboration between GPs and MHDAS to improve quality of care for PLWS especially by monitoring lifestyle and physical health.

Another poorly implemented topic in the long-term management area was the role of ESP patients in peer support interventions. Based on the idea that people who have experienced mental disorders can provide care to others dealing with similar problems (58), peer support programs performed by ESP patients could help other individuals to become more active in their own process of recovery (58). Although some evidence suggested that peer support interventions could exert an effective role improving clinical (i.e., acute care utilization, positive and negative symptoms) (59) and functional outcomes (i.e. recovery) (60), other findings noted that limited data are available to definitively recommend peer support for PLWS (61). Despite these controversial results, as peer support is an essential component of the PLWS journey improving the autonomy and the participation in treatment decision, we deem that MHDAS should further improve this intervention in clinical practice with dedicated plans and awareness campaigns.

The most important result from the survey is that majority of interventions for PLWS were found to be moderately implemented in clinical practice among Italian MHDAS. Indeed, for all the three macro-areas, the implementation levels were moderate, with the highest implementation for the acute phase management and the lowest for long-term management/continuity of care. These results could be interpreted in two different ways: on the one hand, we could suggest that the implementation levels are more than acceptable among Italian MHS. On the other hand, we can observe that clinical practice still requires further strengthening to effectively improve the journey of PLWS as many areas and interventions present some gaps between the importance of the statements and the implementation. As the level of importance for the statements is high for all the investigated areas, we can hypothesize that the heterogeneous implementation levels in clinical practice could be principally attributable to the inter-regional differences in resources allocation and availability that are responsible of the different organization of mental health care at local level. However, this is only a suggestion as this study did not systematically investigate inter-regional differences between local MHS. Moreover, no other studies are available to compare our results, except for our previous survey that examined the Lombardy MHDAS (35). In this case, it was found that, for the early detection and long-term management areas, the degree of implementation in the real-life practice was only moderate-to-good and slightly moderate, respectively, while for the acute phase management, good levels of implementation were found. These data lead to conclude that early phases and chronicity management were the main areas requiring further implementation to improve the journey of PLWS (35). Thus, we can observe that the results of the present survey are substantially in line with those of our previous investigation, with the exception of the acute phase management area.

As moderate levels of implementation emerged for several items, in the following paragraphs we delve into the main areas that could benefit from greater empowerment of clinical actions.