The World Health Organization (WHO) has the strategic priority of achieving Universal Health Coverage (UHC), that means “all people receive quality health services that meet their needs without being exposed to financial hardship in paying for the services” (1). UHC includes rehabilitation interventions among the services to be provided. As part of the WHO Rehabilitation 2030 call for action (2), the WHO Rehabilitation Programme has been developing a Package of Interventions for Rehabilitation (PIR) to support ministries of health in integrating rehabilitation services into health systems (3).

The development of the PIR takes a stepwise approach composed of five consecutive steps: (a) selection of health conditions considering amenability to and the need for rehabilitation, (b) identification of evidence-based interventions for rehabilitation, (c) development of the package with agreement on interventions along with resource requirement descriptions, (d) external peer review, and (e) production of the alpha version of the PIR (3). This paper reports on the second step, which includes the identification of interventions for rehabilitation and related evidence for the health conditions selected in the first step. Under WHO's Guideline Review Committee Secretariat guidance, the WHO Rehabilitation Programme and Cochrane Rehabilitation developed the corresponding methods. Underpinning evidence for the development of the PIR includes a series of systematic reviews of Clinical Practice Guidelines (CPG) for different health conditions selected. Interventions and related evidence identified from these CPG undergo a consensus process to select essential interventions in step 3, to be included in the final PIR. Information related to the provision of the interventions will be added. All information undergoes a review process before developing the final version of the PIR.

Schizophrenia has been selected as one of the priority targets of the PIR. Although not as common as other disabling conditions possibly affecting humans, psychosis resembles the historical antonomasia of mental disability due to its profound long-term effects on individuals, families, and societies. One in 135 people (0.72% of the population), or over 56 million people worldwide, are affected by schizophrenia (4). Proportions are larger in the adult population, due to an incidence peak between the age of 15 and 25 years (4–6). Schizophrenia affects the general population equally, with no substantial difference between males and females, or among urban, rural, and mixed sites (4). Schizophrenia may have a highly detrimental effect on the life of a person and their family, impacting the individual's existence on multiple levels. Especially if left untreated, this condition may progressively deteriorate the personal, familial, relational, educational, and occupational possibilities of a person, accounting for 13.4 million years of life lived with disability globally (6). Profound stigmatization for their condition and their symptoms is the rule rather than the exception for people with schizophrenia across countries, with consequences in terms of social exclusion, isolation, and frequent human rights violation (7–9). This deeply disabling condition is also related to higher odds of dying prematurely due to preventable causes, with a life expectancy of 20 years less than the general population (10, 11).

Despite the high risk of severe, lifelong problems that affect every area of life, around 15% of people with schizophrenia will eventually reach nearly complete recovery (12). The concept of recovery and the concept of rehabilitation share blurred boundaries, and need to be seen as two faces of the same coin. As Anthony (13) well-depicted with regards to recovery from mental illness “Recovery is what people with disabilities do. Treatment, case management, and rehabilitation are what helpers do to facilitate recovery.” Recovery may be related to several interventions, and an early approach is considered pivotal, as highlighted in the recent WHO World Mental Health Report (WMHR), which also emphasized that an holistic multidisciplinary rehabilitation process is key in this population, especially in the long term (14–16). According to WHO, “Rehabilitation helps a child, adult or older person to be as independent as possible in everyday activities and enables participation in education, work, recreation and meaningful life roles such as taking care of family” (17).

Finding a single definition of rehabilitation is challenging, and the differences between rehabilitation for physical and mental health problems add to the difficulty. Since rehabilitation services and techniques have started developing, they sprouted in a multitude of different approaches and theories, sometimes drifting from one another, and leaving a doubt on what rehabilitation actually is. A comprehensive perspective on what constitutes rehabilitation for mental disorders was provided in the consensus statement on psychosocial rehabilitation by the WHO in collaboration with the World Association for Psychosocial Rehabilitation in 1996 (18). In this document rehabilitation is described as “a process that facilitates the opportunity for individuals—who are impaired, disabled or handicapped by a mental disorder—to reach their optimal level of independent functioning in the community,” which is inextricably founded on the individual, the service, and the environment. These concepts kept evolving, broadening the focus not only on “functioning” as part of the social apparatus but also on regaining roles and meaning in each individual life. For example, the Person-Centered Psychiatric Rehabilitation model by Farkas and colleagues (19) states: “Without a process committed to supporting chosen roles and settings, functioning may be improved, but the individual's vision of a meaningful life may still not be achieved. Rehabilitation, therefore, works with social relationships, work, leisure, family life, higher education, and other student pursuits, using interventions that focus on increasing competencies or skills and providing environmental supports.” Similarly, regarding the rehabilitation of mental illness, the National Institute for Health and Care Excellence states: “the guiding principle is the belief that it is possible for someone to regain a meaningful life, despite serious mental illness… it refers to someone achieving the best quality of life they can, while living and coping with their symptoms. It is an ongoing process whereby the person is supported to build up their confidence and skills and resilience, through setting and achieving goals to minimize the impact of mental health problems on their everyday life.” Specifically for the WHO-PIR development, the definition of rehabilitation, used for both physical and mental health conditions, was: “Interventions aiming at improving functioning across all levels of functions (including body functions, activity, and participation) without targeting the cause of the health condition.” Regardless of the specific definition, health systems around the world are urged to put into place appropriate rehabilitation services for people with mental health conditions (16), taking into account the specific individuals, their background and social context, and the available individual and community resources.

Many interventions have shown to be effective as rehabilitation strategies for schizophrenia in well-designed randomized controlled trials. For example, a systematic review on rehabilitation interventions to promote recovery from schizophrenia, identified a total of 80 studies (nine of which were meta-analyses) which consistently provide evidence of the efficacy of interventions such as Cognitive Remediation, Family Psychoeducation, Social Skills Training, and Cognitive Therapy (20). Furthermore, although the healthcare gaps among countries around the world (21, 22), some of these interventions have been successfully implemented in low- and middle-income countries (23, 24). However, given the wide heterogeneity of existing interventions that can be considered as interventions for rehabilitation, policy makers, stakeholders, professionals, and service users may find it difficult to navigate through alternative intervention options and make informed decisions. Some CPG have been developed to organize and summarize existing evidence, but the field of rehabilitation in schizophrenia is still fragmented and somewhat contradictory in terms of recommendations. Therefore, as a base for the WHO PIR, we conducted a systematic review of existing CPG relevant to rehabilitation of people with schizophrenia.

This systematic review of CPG has been developed in full compliance with the methodology presented in the introductory WHO PIR protocol of research (3). These stages have been followed (Figure 1):

Topics/areas considered by the selected CPG into each main type of recommendation (assessment and intervention) have been extracted. Recommendations regarding the management of the acute phase of illness, recommendations on medications and side-effects, as well as service recommendations were excluded, therefore leading to a selection of non-drug-related recommendations on the long-term course of the treatment. The topics (functioning domains) from different CPG have been compared independently by two authors and integrated. If needed, agreement by discussion was reached involving a third author. The process has been repeated for all the CPG until final agreement on the topics was reached.

Results of the literature search are shown in Figure 1, in agreement with the PRISMA statement (26). A total of nine CPG were selected on the basis of abstract and full-text screening. Details on the abstract and full-text screening are shown in Supplementary Table 1. As shown in Table 1, three of these were excluded due to a total AGREE-II score <45 (27–29), leading to the inclusion of six guidelines (25). The six CPG were approved by the Technical Working Group and included for data extraction:

In addition to the selected CPG, relevant WHO guidelines including mhGAP Evidence-based recommendations for management of psychosis and bipolar disorders in non-specialized health settings as well as management of physical health conditions in adults with severe mental disorders were included for the development of PIR. However, these resources have not been included in this review.

The topics (functioning domains) extracted from included CPG are presented by type of recommendation (assessment/intervention) in Table 2. The original recommendations from included CPG, related quality of evidence (QoE) and the strength of recommendation (SoR) are presented in Table 3. As seen in Table 2, different topics of intervention are resumed in the first column, and each line presents the number of interventions on that specific topic for each included CPG. Recommendations are reported multiple times if the original recommendation included multiple target outcomes or multiple interventions for the same target. SoR and QoE are presented in a standardized fashion to avoid discrepancies in terms used among CPG. Rationale applied to this classification and original classifications are presented in Supplementary Table 2. Among all CPG, only NICE-3 had a specific focus on the rehabilitation of schizophrenia (35).

For assessment recommendations, “Mental/Emotional functions” and “Education and Vocation” were the functioning domains with the highest number of recommendations. Assessment recommendations for “Interpersonal interactions and relations,” “Exercise and fitness,” and “Speech, language and communication” were provided in NICE-3, and “Activities of daily living” in NICE-1 and NICE-3. In terms of providing specific assessment recommendations, “self-management” or “community and social life” domains were not addressed in the CPG.

Regarding intervention recommendations, all six CPG provided many recommendations addressing “symptoms of psychosis” which was the domain with the highest number of recommendations. A high number of interventions were also provided for “Education and Vocation” and “Self-management,” 12 and nine, respectively. All CPG, except for SIGN and NICE-1 respectively, addressed “Education and Vocation” as well as “Mental/cognitive functions” and “Interpersonal interactions and relations.” A total of six domains, out of 13 were targeted by low number of recommendations (4 or less) including “community and social life” (addressed by NICE-3), and “activities of daily living” (addressed by NICE-3 and DGPPN).

The QoE for given recommendations was high for 20.77% (n = 27) of the recommendations. The same number of recommendations had a moderate QoE (n = 27; 20.77%) while n = 20 (15.38%) had low QoE. Only two recommendations (1.52%) had very low QoE, and nine (6.92%) were based on U.K. prevalence studies. A total n = 45 (34.62%) of the recommendations is based on experts' opinions. Experts' opinions are used for recommendations on generally good clinical practice (e.g., informing carers on their statutory rights. See Table 3), as well as to support clinically available interventions in lack of sufficient available evidence (e.g., “We suggest offering cognitive remediation in combination with other psychosocial and rehabilitative treatment methods”). SoR is strong for more than half of the recommendations (n = 81; 62.3%). Within these strong recommendations, n = 25 is based on Experts' opinion. A minority of recommendations (n = 37; 28.46%) is conditional, while the rest (n = 12; 9.23%) indicates no strength of recommendation and is based on Experts' opinion.

In this systematic review we summarized existing recommendations from high-quality CPG on rehabilitation interventions for people with schizophrenia. Only one CPG with a specific focus on the rehabilitation of schizophrenia was found. This suggests a gap in current CPG production process, with a relative lack of information on this topic. This seems particularly relevant in view of the recent publication of the WHO World Mental Health Report (WMHR), which urges nations and professionals to work toward empowering people to regain independence and live a life in full autonomy through the implementation of recovery-oriented interventions, most of which may be categorized as rehabilitation interventions (16).

Despite the scarcity of CPG on rehabilitation of schizophrenia, we identified general CPG that included several recommendations that are, either directly or indirectly, relevant to the assessment of rehabilitation needs and to the provision of rehabilitation interventions. To our knowledge, this is the first systematic overview of recommendations in this important field of intervention, which will be used to inform the WHO PIR and, hopefully, it may also be of interest to countries and professionals aiming to fully implement the concept of rehabilitation, in line with the WHO WMHR.

In terms of quality of available evidence, only a minority of target domains and recommendations are supported by high-quality evidence. Notably, expert opinions often supported recommendations on good clinical practice as well as on specific interventions, even in absence of a supporting background body of evidence. This applies, for example, to recommendations on physical activity, or those on the combination of individual and family interventions, or those in favor of supported employment. Despite this relatively low quality of background evidence, the strength of many of these recommendations was strong. This is in line with current standards of CPG development, as in addition to the evidence base, other considerations, such as for example values, preferences, feasibility and equity considerations should also be considered in drafting recommendations and their strength. We note, therefore, that in the field of rehabilitation there is a discrepancy between the scarcity of data on one side, and the high value attributed to rehabilitation interventions by professionals and by a variety of different stakeholders, including people with living experience of mental health conditions, on the other side. Increasing research and knowledge about this complex subject could increase clarity on what the key elements of rehabilitation in schizophrenia are. Research in this field however is hard to conduct due to long follow-up times, heterogeneous settings, complex outcomes, and lack of resources.

Looking at the total number of recommendations on specific topics (functioning domains, Table 2), some areas are not addressed adequately by available CPG, for example “Activity of daily living,” “Interpersonal interactions and relations,” “Community and social life,” and “Carer and family support.” Conversely, we included 16 recommendations addressing “symptoms of psychosis.” This disbalance is probably related to the inconsistent definition of rehabilitation in this field, and to an increased difficulty in effectively research outcomes such as “community involvement and social life” (in opposition to the reduction of psychotic symptoms).

The concept of rehabilitation is tightly related to the concept of recovery which, in the field of mental health, gained prominence after the implementation of deinstitutionalization with ever greater relevance of community services and interventions to help people achieve recovery. Recovery from a mental illness has been described as “a deeply personal, unique process of changing one's attitudes, values, feelings, goals, skills, and/or roles. It is a way of living a satisfying, hopeful, and contributing life even with limitations caused by illness. Recovery involves the development of new meaning and purpose in one's life as one grows beyond the catastrophic effects of mental illness” (13). A more recent definition has been formulated by merging the professionals' most commonly cited themes describing the meaning of the term rehabilitation which reads: “A whole system approach to recovery from mental ill health which maximizes an individual's quality of life and social inclusion by encouraging their skills, promoting independence and autonomy in order to give them hope for the future and which leads to successful community living through appropriate support” (36). Ultimately, in accordance with the WHO WMHR, if recovery from a mental disorder is the process of regaining a better mental health, rehabilitation is the body of procedures helping the individual in this process and fostering the ability to connect, function, cope and thrive (16). Further promoting a switch of paradigm from a “hospital/asylum-centric” approach to a community-centered care at a policy-making level, will stimulate the research and implementation of rehabilitation techniques focusing on recovery rather than pure reduction of symptoms (15). Still, it has to be considered that schizophrenia is a lifelong condition characterized by prodromal and residual subclinical disturbances, having implications in chronic disability (37, 38), with a 3.5%−11% per month risk of abrupt relapse to the pre-treatment condition for treatment adherent and non-adherent people in treatment for psychoses respectively (39, 40). Therefore, the long-term management and reduction of key symptoms have to be taken into account in the rehabilitation of schizophrenia as one of the factors involved in long-term recovery.

This review needs to be interpreted in the light of some limitations. First, CPG should be considered with a recognition of their inherent limitations. These recommendations are formulated based on the currently available evidence and do not encompass all potential actions required to mobilize community resources and opportunities, strengthen social cohesion and social capital, and overall integrate formal and informal care services while considering the local context. Nonetheless, the absence of these considerations does not imply that such actions should be excluded from intervention programs. All parties involved should acknowledge the importance of tailoring rehabilitation projects to accommodate individual, familial, and cultural contexts, as well as the location of service delivery, in order to ensure effective implementation. Clinicians are therefore urged to make a concerted effort to integrate evidence-based CPG with the specific needs of individuals who have experienced mental disorders. By doing so, they can provide guidance that empowers individuals to utilize resources, tools, and opportunities that align with their personal aspirations, as well as their social and clinical circumstances. A second limitation is inherent to the systematic review methodology itself, due to the potential exclusion of titles, and therefore potentially relevant information, not emerging from the literature search. In this regard, the strings used for this research were developed on the basis of the WHO indication on the systematic search of literature for the development of the PIR for all conditions. Another limitation arises from the sole inclusion of English language CPG, which was driven by feasibility considerations. We recognize that the omission of CPG in other languages could pose a significant constraint, as the outcome of the current review may predominantly reflect Western practices. Consequently, contexts in which alternative approaches, involving for example non-specialist community workers, volunteers, activists, and peers, play pivotal roles may not have received sufficient visibility.

In conclusion, six CPG based on available evidence, relevant WHO guidelines and expert opinion will inform the development of the WHO PIR for schizophrenia and related psychosis. This review revealed an imbalance in the domains addressed and a lack of indications in poor-resource settings. Priority targets and interventions in the rehabilitation in schizophrenia are still unclear in terms of significance and feasibility.

The scientific community is called to embrace the challenge posed by the WHO WMHR 2022 (16). To promote a more thorough and holistic approach to rehabilitation in this field, it will be important to research on and implement pragmatic solutions in somewhat neglected areas of the rehabilitation of schizophrenia such as “Community and social life.” Within the WMHR logic, supporting people in accessing health and social services, such as psychosocial rehabilitation, housing, or welfare benefits, are all crucial aspects of care. All these actions ought to be carried out with the intention of fostering community involvement, engagement, and legal ability. The WHO PIR will help face this important challenge in the field of schizophrenia.

Conceptualization: RS, YE, CB, and LT. Methodology: YE, MR, CB, and LT. Software: RS and YE. Formal analysis: RS. Investigation: RS, YE, and MR. Resources: CB and LT. Data curation: RS, YE, MR, and LT. Writing—original draft preparation: RS and LT. Writing—review and editing: CB, YE, and MR. Project administration: YE, CB, and LT. All authors have read and agreed to the published version of the manuscript.