Introduction

The clinical high risk for psychosis (CHR-P) paradigm1 represents one of the most established preventive approaches in clinical psychiatry2. It originated in Australia around 25 years ago3 and since then, it has progressively gained importance4. CHR-P individuals are young and accumulate risk factors for the disorders5,6,7, that lead to functional impairments8 and attenuated psychotic symptoms9. Because of these features, these individuals seek help10 at specialised CHR-P mental health services. The detection11, prognostic assessment12 and preventive treatment13,14,15,16 in CHR-P individuals15 have the potential to maximize the benefits of early interventions in psychosis17,18. A recent evidence-based summary by the European College of Neuropsychopharmacology Network for the Prevention of Mental Disorders and Mental Health Promotion19 indicated that the first rate-limiting step to prevent psychosis is to establish specialised CHR-P services20. Accordingly, several CHR-P services have been implemented worldwide, as recently mapped by the International Early Psychosis Association (IEPA21: https://iepa.org.au/list-a-service).

Despite these progresses, health service research in this field has been fragmented to the point that the characteristics (“what”) of a CHR-P service per se are poorly defined. As CHR-P services expand globally21, it becomes essential to synthetize the core CHR-P health service features that have been implemented in real-world scenarios. While a CHR-P clinic can be broadly defined as a “multidisciplinary community mental health service that provides treatment and support to people at high risk of developing psychosis” (page 16 from NHS England22), this definition remains elusive. Similarly, there is no clear guidance on “how” to integrate different service components. The three main models for delivering CHR-P services include the “stand-alone”, “hub and spoke”, and “integrated” models22. While the standalone model works independently from other more generic community mental health teams, in the “hub and spoke” model, dedicated team workers (“spokes”) are based within more generic community teams to route patients needing more intensive services to the central “hub”23. In an integrated model, the CHR-P service is completely integrated into the community mental health care. In addition, these models can be combined within broad mental health services enhancing transitional primary care platforms across adolescents and young adults24. The additional limitation of knowledge is that the timing (“when”) for preventive approaches, which is reflected by CHR-P entry age criteria is uncertain. While this has been typically set for young people aged 8–404 years, more recent lifespan-inclusive approaches for those under the age of 25 (0–25 years)25 models have been piloted.

While previous systematic reviews have addressed these issues for services taking care of patients with a first episode of psychosis26,27, CHR-P research has remained mostly “academic” and did not systematically address real-world service characteristics such as: service configuration, outreach strategy and referrals, service user characteristics, interventions, and outcomes. The current systematic review summarizes, for the first time, evidence on these domains to inform the real-world implementation (i.e., what, how, and when) of CHR-P clinical services worldwide.

Methods

This study (study protocol: PROSPERO CRD42020163640) was conducted in accordance with PRISMA28 (eTable 1) checklist.

Search strategy and selection criteria

A multistep systematic literature search strategy was used to identify relevant articles by two independent researchers (GSP, AE). First, the Web of Science database (Clarivate Analytics) was searched, incorporating the Web of Science Core Collection, BIOSIS Citation Index, KCI-Korean Journal Database, MEDLINE, Russian Science Citation Index, and SciELO Citation Index as well as Cochrane Central Register of Reviews, and Ovid/PsychINFO databases, as well as the OpenGrey database (for grey literature) from inception until 4th May 2020, with no restrictions on language. The following search terms were applied: (“risk” OR “prodrom*” OR “ultra-high risk” OR “clinical high risk” OR “attenuat*” OR “high risk” OR “genetic high risk” OR “risk syndrome” OR “at risk mental state” OR “at-risk mental state” OR “ARMS” OR “risk of progression” OR “schizophrenia” OR “schizoaffective disorder” OR “schizophreniform disorder”) AND (“psychosis”) AND (“prevention” OR “intervention” OR “early intervention” OR “referral” OR “assessment” OR “service” OR “clinical service” OR “psychiatric service” OR “implementation” OR “care pathways”). The references of the articles identified in previous reviews and relevant commentaries and the references from the included studies were manually searched to identify additional relevant records. Abstracts were screened, and potential full texts were assessed against inclusion and exclusion criteria.

The inclusion criteria were a) being an original study published in international databases or in the grey literature, b) describing clinical services for individuals in a CHR-P state as defined according to established instruments: Comprehensive Assessment of At-Risk Mental States (CAARMS3), Structured Interview for Psychosis-risk Syndromes (SIPS29,30), Bonn Scale for the Assessment of Basic Symptoms (BSABS31), Basel Screening Instrument for Psychosis (BSIP32), Schizophrenia Proneness Instrument33 - Adult (SPI-A) and Child and Youth (SPI-CY) version -, Positive and Negative Syndrome Scale (PANSS34), Scale for the Assessment of Negative Symptoms (SANS35), Brief Psychiatric Rating Scale (BPRS36) and Early Recognition Inventory (ERIraos37), c) providing information on any of the following: service configuration, outreach strategy and referrals, service user characteristics, interventions and outcomes, d) providing relevant information without any restrictions on language, sex, age, or ethnicity. The exclusion criteria were a) non-original studies such as abstracts, conference proceedings, study protocols, reviews, guidelines, b) studies with a primary research focus (e.g., research networks) and lacking description of CHR-P clinical services, c) studies describing clinical services for conditions other than the CHR-P or services without a CHR-P component, d) national or regional survey studies with aggregate data and lacking a service-specific description.

Descriptive measures and data extraction

Independent researchers (GSP, AE, MC) extracted data from the included studies; discrepancies were resolved through consensus, consulting a senior researcher (PFP). The variables included were those necessary to describe “what, how and when” to implement CHR-P services. These variables were grouped according to health service domains previously established (beyond general data such as first author, year of publication, name of the CHR-P service, country)38: (i) service configuration: continent, service set-up date, population in the catchment area, type of service, professionals involved, (ii) outreach strategy and referrals: outreach activities—measured using an adapted version of the Longitudinal Youth-At-Risk Study (LYRIKS) study39 classification—, referral sources (iii) service user characteristics: sociodemographic characteristics, CHR-P assessment, CHR-P subgroups (defined as in previous studies)40, minimum and maximum age inclusion criteria and service use age range, comorbidities and employment (iv) interventions: type of intervention (non-pharmacological vs. psychopharmacological) and duration of service provision and (v) outcomes: type of outcomes monitored and outcome instruments. Furthermore, we reported quality assessment (see below).

Data analysis

Systematic review

All the studies were systematically summarized in tables reporting on various health service domains: service configuration, outreach strategy, and referrals (Table 1), service user characteristics (Table 2), interventions and outcomes (Table 3). We complement this with descriptive analysis of common operational and clinical challenges. An online tool (https://www.maptive.com) was used to create a graphical representation of the geographical distribution of the CHR-P services included in the review.

Table 1 Service configuration (above); outreach strategy and referrals (below).
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Table 2 Service user characteristics.
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Table 3 Interventions (above) and outcomes (below).
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Quality assessment

We adapted the mixed Methods Appraisal Tool (MMAT)41,42 questions for non-randomized clinical studies due to the heterogeneity expected in the included studies to assess the quality of the included studies (eMethods 1), considering the content and characteristics of the studies according to our inclusion criteria.

Results

Database

The literature search yielded 12,130 citations, which were screened for eligibility. Two hundred and twenty-one full-text articles were evaluated for eligibility, and 165 were excluded. In total, 49 studies reporting information on individual CHR-P services (eTable 2), and seven multisite studies (eTable 3) were selected (PRISMA, Fig. 1). All CHR-P services (100%) used validated assessment instruments and no studies were excluded for this reason. The final pool of 56 included studies were published between the years 1998 and 2020. The total sample encompassed 51 distinct CHR-P clinical services, from 41 different regions, across 15 countries (Fig. 2).

Fig. 1: PRISMA Flowchart.
figure 1

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flowchart outlining study selection process.

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Fig. 2: CHR-P services map.
figure 2

Geographical distribution of CHR-P services included in the review.

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Most multisite studies reported on collaborative networks of clinical CHR-P services, including the Pan-London Network for Psychosis-Prevention (PNP38), the Early Detection and Intervention for the Prevention of Psychosis Program (EDIPPP43,44,45), and the Swiss Early Psychosis Project (SWEPP46). Two additional multisite studies report on five centres operating under the Italian Departments47 and six CHR-P services in Canada48.

Service configuration

The CHR-P services were located mostly in Europe (58.8%), followed by North America (25.5%), Australia (7.8%), Asia (5.9%), and South America (2.0%; Fig. 2 and Table 1). The first program to be implemented was the Personal Assessment and Crisis Evaluation (PACE) clinic in 1994, in Melbourne49, and the most recent one the City & Hackney At-Risk Mental State Service (HEADS UP) in 2015, in London38. 62.0% CHR-P services were set up from 2000 to 2009 (Table 1). Population in the catchment area covered a total of 17,252,666 people, with an average of 492,933 people (SD: 396,997, Table 1). Most services (80.4%) consisted of teams integrated into the community mental health care. Standalone CHR-P services were less frequent (19.6%) and there were no hub and spoke services. CHR-P clinical services involve a wide range of professionals, the most frequent ones being psychiatrists (100%), who were involved in all the services. Other professionals include clinical psychologists or counsellors (76.7%), case managers/care coordinators (50%), and nurses (50%).

Outreach strategy and referrals

Outreach activities and audiences were highly variable (Table 1). Within active strategies, workshops for referral sources were the most frequent (97.6%), often targeting healthcare professionals (85.4%), educational professionals (48.8%), or community organisations (34.1%). Services also approached NGOs and community services (34.1%), and less frequently social and governmental services (19.5%) and family members of mental health patients (4.9%). About one-third of CHR-P services (36.6%) implemented general public awareness campaigns including TV or radio appearances50,51, theatre adverts, high school art contests, and sponsors for minor league sports teams45. More than half of services (63.4%) implemented either a dedicated online site for service promotion, or have elaborated printed and other media materials (53.7%), such as information brochures and leaflets50,51,52, posters53, articles in professional journals and local newspapers51,54, presentations in scientific conferences46, newsletters51, and promotional videos43,55. Most CHR-P services received young people with a putative risk of psychosis from health-related organizations, including both outpatient or community mental health services (90.0%) and general healthcare services (75.0%). Education organisations are also frequent referral sources (65.0%), followed by self (60.0%), family or relatives (60.0%), inpatient mental health services (42.5%), and accident and emergency departments (22.5%). Other referral sources were reported in less than 20% of CHR-P services.

Service user characteristics

The total sample size of service users was of 5637 CHR-P individuals, ranging from 456 to 46757 individuals: most of them were males (% of CHR-P females = 42.8, see Table 2).

CHR-P status was most frequently assessed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) (48.6%), followed by the Structured Interview for Psychosis-risk Syndromes (SIPS) (35.1%) and the Early Recognition Inventory retrospective assessment of symptoms checklist (ERIraos-CL) (16.2%; Table 2). The Basel screening instrument for psychosis (BSIP) and basic symptoms instruments were infrequently used (<6% of services). Most services provided treatment starting in adolescence, from the ages 12 to 17 (83.4%). The most frequent minimum inclusion age range was 13–15 years (31.3%); only two services reported the inclusion of children from the age of 8 and 646,48,58. Most services accepted users until 30–35 years (49.0%) or 24–29 years (28.6%). A few services (6.1%) accepted service-users of 65 years or older56,59. The most frequent age range (70.6% of services) was 12 and 35 years.

82.6% of the CHR-P individuals fulfilled APS criteria, 10.7% fulfilled BLIPS criteria and 8.5% fulfilled GRD criteria (not mutually exclusive). Baseline comorbid mental disorders were reported in 69.5% CHR-P individuals. Mood disorders were the most common: depressive disorders (42.3%), bipolar disorders (15.5%), and persistent depressive disorder (6.7%). Anxiety disorders were also frequent (24.1%), including social phobia (5.9%) and obsessive–compulsive disorder (OCD) (5.1%). Adjustment disorder appeared in 11.6% of CHR-P individuals. Comorbid personality disorders were present in 15.5% of CHR-P individuals, particularly schizotypal personality disorder (11.0%). Substance use disorders were present in 12.4% of CHR-P individuals. Past history of suicide attempts was present in 10.5% of CHR-P subjects. Unemployment rate (i.e., neither work nor study) was observed in 36.6% in CHR-P individuals in clinical services.

Interventions

Across non-pharmacological interventions, clinical monitoring was the most common intervention and was carried out in all the services (100%). Other common interventions were psychoeducation (81.1%), case management and psychosocial support (73.0%) and family interventions (73.0%) (Table 3). Cognitive behavioural therapy-based interventions and any other type of individual psychotherapeutic intervention (encompassing individual motivational interviewing60 or sessions47, supportive counselling38,44,47,49,52,61,62,63,64,65,66,67,68,69,70,71, relaxation training61, cognitive remediation55, solution focused brief therapy55, social skills training65,70, substance misuse work70, and psychotherapy NOS72,73) were provided by about two-thirds of the services (67.6% and 64.9%, respectively). Physical health interventions and group psychotherapy sessions were more infrequent (37.8% and 18.9%, respectively).

Most (87.1%) services employed low-dose antipsychotic (AP) medication, although not as the first-line intervention but only following worsening of symptoms or functioning52,74,75. Other interventions employed by CHR-P services included antidepressants (74.2%), anxiolytics (51.6%), mood stabilisers (38.7%). Three services (9.7%) reported the use of omega-3 fatty acids38,66,71,76,77. Most services provided care for 24 months (44.8%) or 12 months (24.1%). Three services (10.3%) provided 36 months of clinical follow-up. Extended service provision of 60 months or more were reported in 17.2% of services.

Outcomes

The outcomes most frequently evaluated in the CHR-P services were persistence of symptoms/comorbidities (67.4%), transition to psychosis (53.5%), functional status (48.8%), and remission (41.9%). Physical health outcomes (30.2%), service users’ satisfaction (25.6%), hospitalisation (18.6%) and mortality (13.9%) were less frequently evaluated.

Outcomes were most commonly evaluated with standard clinical interviews with the service users (93.0%), and more infrequently with psychometric instruments (37.2%). In the latter case, the CAARMS (23.2%) and SIPS (11.6%) were more frequently employed. About 16.3% of CHR-P services evaluated outcomes via electronic health records.

Quality of the included studies

Study quality scores ranged from 1 to 5. The overall mean quality score for included studies reporting on individual services was 3.8 (moderately high quality) on the MMAT scale, with a SD of 1.3 (eTable 2).

Discussion

To our knowledge, this is the first systematic review to comprehensively summarize the evidence from real-world implementation of CHR-P clinical services. This review encompasses 56 studies describing a total of 51 services for CHR-P individuals.

Consistent with recent surveys of CHR-P services21,47,78, there is great diversity in how clinical services have been implemented in real-world scenarios, across all aspects of service delivery: 1) service configuration, 2) outreach strategy and referrals, 3) service user characteristics, 4) interventions and 5) outcomes. We discuss these points, while also mentioning common challenges. The evidence summarised will then be used to operationalise ten empirical recommendations for overcoming these challenges and facilitating the real-world implementation of CHR-P services (Table 4).

Table 4 Ten simple recommendations for real-world implementation of CHR-P service.
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In terms of service configuration, several CHR-P clinical services have been implemented across—at least—15 countries (Fig. 2), covering a catchment area of over 17 M people. Following a period of rapid expansion (2000–2009), new CHR-P services continue to emerge38,76. At present, CHR-P services spread across most continents21, although they are mostly established in high-income countries. While most CHR-P services are configured as integrated services (80.4%), standalone models of care (19.6%) seem to be associated with high levels of service efficiency27. For example, CHR-P standalone services had dropout rates in the range of 12–19.2%50,77,79,80,81,82 compared to 25.4% in integrated services52. One possible explanation is that in integrated models of care, healthcare resources are typically diverted towards more severe service users (e.g., first-episode vs. CHR-P patients)38. In line with this notion, the actual caseload of CHR-P individuals was minimal (n = 4 out of 239 clients) in some integrated services56, and more severe patients had more frequent contacts with these services73. Another issue is that standalone services may be physically located outside general psychiatric services, which is preferable to reduce stigmatisation risks77,81. Service users and their relatives were generally more satisfied with standalone CHR-P services, particularly with clinical contact being outside traditional mental health settings67. Conversely, family disengagement was the most significant barrier (71.4%) in integrated services60. Likewise, primary care clinicians favoured standalone models of care because of the superior accessibility of the services67. Standalone services are more costly to set up in the first year but deliver highest economic savings in the longer term69, mainly associated with the improved outcome of the disorder68. These considerations are of relevance given that poor financial support and lack of adequate infrastructures are frequently cited barriers for the establishment of standalone CHR-P services outside mental healthcare21. Future health service research is expected to consolidate these speculations, as well as to test the efficiency of innovative models of care. For example, although there were no hub and spoke services, this organization design, which arranges service delivery assets into a network, may be particularly promising in this field and fit well with the youth friendly mental health reform which is undergoing in several countries83. Based on this evidence we recommend to preferably implement standalone services (Table 4).

This review also indicates that the CHR-P clinical services are essentially multidisciplinary, reflecting the complexity of the psychopathological assessment and case formulation84. Based on the most frequent professionals involved in CHR-P services, we recommend a minimum team encompassing psychiatrists, clinical psychologists, or counsellors, case managers and nurses (Table 4). Because multidisciplinary work requires adequate articulation and training of staff, a core associated recommendation is to ensure adequate training85. National surveys have found lack of specialised training in evidence-based interventions to cause dismal across staff78,86. Ensuring proper training is particularly challenging for non-academic services, with less resources and limited organizational support48.

In terms of outreach strategy, school, mental health, and physical health practitioners were the core targets of community outreach43. We have confirmed high heterogeneity across two main strategies: active (up to 97.6%) and passive (up to 63.4%) outreach. The first strategy involved active efforts to organise workshops more frequently targeting healthcare professionals (85.4%), or service promotion activities in the community (up to 34.1% of CHR-P services) and implementing general public awareness campaigns (36.6%). The second strategy involved passive approaches such as a dedicated online site (63.4%), or printed and other media materials (53.7%). This heterogeneity is likely to reflect diverse culturally sensitive approaches across CHR-P services that led to variable pathways to care. In terms of referrals, most CHR-P services received young people with a putative risk of psychosis from health-related organisations such as mental health services (90.0%) and general healthcare services (75.0%). Implementing an outreach to promote referrals of CHR-P individuals is challenging. In the lack of clear guidance, there is high risk of inefficient use of resources (e.g., staff) and inappropriate referrals that eventually do not meet CHR-P criteria. For example, some CHR-P services reported a high number of inappropriate referrals following intense media campaigns, switching to more focused outreach strategies49,51,61,79,87,88,89,90. At times of financial constraints, the core outreach activities and referral targets summarised in the current study can be used as benchmark to maximise the efficiency of resources when implementing a new CHR-P service. There are also empirical constraints. For example, difficulties in recruiting participants is the most difficult challenge in countries where the CHR-P paradigm is starting to be implemented76 and in culturally diverse catchment areas43. Even in countries with an established CHR-P network like the UK, increasing numbers of referrals following the implementation of new national policies resulted in more dedicated CHR-P services that were needed to manage the referrals59. Finally, the type of outreach and referrals determine the accumulation of established risk factors for psychosis5,7,91, thus influencing the level of psychosis risk among individuals recruited for undergoing a CHR-P assessment (also termed as pretest risk enrichment)92,93. For example, individuals sampled from inpatient units may have accumulated more risk factors for psychosis and therefore present with a higher level of psychosis compared to those sampled from the community. This level of risk enrichment93,94, substantially impacts the clinical utility of CHR-P instruments12. Accordingly, intense outreach strategies mainly targeting the general population end up diluting the level of pretest psychosis risk93, and therefore impeding a clinically meaningful identification of CHR-P individuals11,95. In line with recent psychometric guidances12,20, we recommend CHR-P outreach to primarily target healthcare agencies to promote referrals from these sources (Table 4). Community outreach and recruitment from the general public should be considered only if adequate risk enrichment strategies can be implemented (for a detailed review see ref. 11). For example, pre-screening approaches can increase pretest risk enrichment among referrals21 and was employed by some services47.

In terms of service users characteristics, we confirmed that males were relatively more represented than females, in line with the epidemiological gender distribution of psychosis risk6. Currently, the vast majority (83.7%) of CHR-P services employ the CAARMS or the SIPS, while basic symptoms instruments failed to enter clinical practice at large scale. This suggests that the harmonisation of these two instruments could deliver a widely used gold standard assessment measure for clinical practice. A rapid response to referrals62 and flexibility with time and setting of assessments67 have been found to improve engagement with CHR-P services.

Age intake is a core implicit criterion (along with the help-seeking behaviour) defining the CHR-P state4,10,20. The most frequently applied age range (70.6% of services) was of 12–35 years, in line with epidemiological research indicating that the peak of risk is between 15 and 35 years6. Empirical research confirms that CHR-P psychometric assessment (e.g., the CAARMS) is valid in young people aged 12 years upwards64. This finding also confirms the transitional nature of the CHR-P paradigm that cuts across adults and children and adolescent mental health services25. Accordingly, most services provided treatment starting in adolescence (between 13 and 15 years). Conversely, only a few services accepted users beyond 40 years56,59,96. The requirement of extending the assessment and care of emerging psychosis in the older people, introduced by national guidelines such as the Access and Waiting Time Standards in the UK22 is against the evidence that CHR-P instruments are valid up to 40 years4. Furthermore, it conflicts with recent mental health reforms that are lowering—as opposed to increasing—the age threshold for preventive approaches to those aged from 0 to 25 years25. Based on these findings we recommend that CHR-P services ascertain the at-risk status through the CAARMS or SIPS in both adolescents and young adults (Table 4). This review also indicated that presentation to CHR-P services was associated with frequent comorbid mental health conditions (in particular mood and anxiety disorders97,98) in two-thirds (69.5%) of the individuals, coupled with past history of suicide attempts in about one in ten (10.5%) and unemployment in about one third (36.6%) of cases. We further observed regional heterogeneity in clinical presentation: substance misuse was more prevalent in Western services38,51,54,60,65, while non-existent in Japan52. These findings recommend that CHR-P services should adopt a broader “transdiagnostic” approach”99,100,101, which is cutting across several psychopathological dimensions (Table 4), given that psychosis onset can occur from preceding mood dysregulation102 or substance abuse. This recommendation is also relevant for current operationalisations of at-risk syndromes, which require formulating a differential diagnosis between psychosis risk and other psychopathological dimensions such as the SIPS or the DSM-5-APS2. Although psychotic experiences are frequent in the general population103,104, clinical attenuated psychotic symptoms are infrequent and not normally distributed. Only 0.3% of the general young population meet DSM-5-APS criteria2,105.

In terms of interventions, most services (72.4%) provided care for 2 years or less (see outcomes below), with some exceptions38,48,52,54,55,62,63,72,74,81,87,106, encompassing clinical monitoring (100%), psychoeducation (81.1%), psychosocial support (73%), family interventions (73%), CBT-based individual interventions (67.6%), group psychotherapy (18.9%), physical health interventions (37.8%), antipsychotics (87.1%), antidepressants (74.2%), anxiolytics (51.6%), and mood stabilisers (38.7%). It appears that CHR-P clinical services currently provide a wide range of psychosocial and biological interventions to meet the clinical needs of CHR-P service users. Clinical monitoring, case management and targeted case management are essential elements of preventive treatment22, based on the principles of social psychiatry and the importance of engaging CHR-P individuals with healthcare services107. These often included psychoeducation and informing patients about their risk, as done in other preventive approaches in medicine84. Despite current guidelines recommending psychological interventions (such as cognitive behavioural therapy) as first-line treatment, about one-third of CHR-P services did not provide them. Evidence to favour psychotherapy over other types of interventions in this population is currently uncertain13,15,16,20. Conversely, antipsychotic treatment, which is discouraged by current treatment guidelines, was frequently considered, although typically at low dosages and only when the symptoms were deteriorating. This is consistent with data from global and national surveys of CHR-P services21,78 that report frequent use of antipsychotic drugs. The relatively frequent use of anxiolytics, antidepressants, and mood stabilizers—which is not considered by current guidelines—can index the transdiagnostic nature of the CHR-P state with frequent affective and anxiety comorbidities. The variety in provision of treatments likely reflects the high clinical heterogeneity of this population and the lack of clear treatment guidelines stratified on their individual needs. For example, current guidelines are not stratified across CHR-P subgroups. Individuals with brief psychotic episodes may be defined through research-based operationalisations, such as brief and limited intermittent psychotic symptoms (BLIPS) or standard psychiatric classifications including “Acute and Transient Psychotic Disorder” as per ICD-11 or DSM-5 “Brief Psychotic Disorder”. There is diagnostic and prognostic overlap across these definitions of brief psychotic episodes108,109. Individuals with brief psychotic episodes have the highest risk of developing psychosis20—especially when recurrent or presenting with seriously disorganizing or dangerous features—108,110. They also display poor clinical outcomes and do not engage with the recommended cognitive behavioural therapy40,108, leaving them with unmet need for care110. Stratification across these clinical subgroups has been proposed in recent revisions of the CHR-P paradigm1,20 and should be considered in future clinical guidelines21. Because the uncertainty of current evidence is high, we align with the recent recommendations of the European College of Neuropsychopharmacology Prevention of Mental Disorders and Mental Health Promotion Network19 to still offer needs-based interventions and psychological interventions, titrating the intervention according to the characteristics and risk profile (i.e., transition risk, symptom severity, and functional impairment)20 as well as the values and preferences of the CHR-P individuals (Table 4)20. For example, it seems important to individualise physical health and lifestyle interventions on the needs presented by each service user60,76.

In terms of outcomes, surprisingly, persistence of symptoms/comorbidities (67.4%) was measured more frequently than transition to psychosis (53.5%), functional status (48.8%), and remission (41.9%). This likely reflects the efforts of CHR-P services to treat comorbid conditions, aiming for improving recovery, functioning, and quality of life20. At the same time, other outcomes such as physical health were collected in only about a third (30.2%) of CHR-P services111. CHR-P individuals accumulate genetic and environmental risk factors20, including cardiometabolic risk factors as decreased physical activity112 and high rates of substance use112, including tobacco112, alcohol112, and cannabis113. Thus, more attention should be paid to recording the physical health of CHR-P individuals in clinical services114. Another domain of improvement includes a more frequent monitoring of service users’ satisfaction, which is pivotal to higher engagement and decreased drop-out rates. Furthermore CHR-P services should also more extensively monitor healthcare utilisation (e.g., hospital admissions)115 and broad outcomes such as mortality rates to better characterise the overall burden of this condition116. Future research is needed to standardise a core outcome set for CHR-P research and therefore facilitate collaborative efforts. These initiative should also indicate the assessment measures to be employed to monitor outcomes. Currently, clinical outcomes in CHR-P services are most commonly evaluated with standard clinical interviews (93.0%), and psychometric instruments are more infrequently used (37.2% of cases, most frequently CAARMS or SIPS to evaluate transition to psychosis)20. In the future, monitoring broad health outcomes in CHR-P services could leverage electronic health records that can provide real-world, real-time valuable clinical information11,117,118,119,120 and that are being increasingly implemented in healthcare providers. As noted above, duration of care including clinical monitoring is currently limited to, most frequently (44.8%), 2 years. However, accumulating evidence has clearly indicated that although the risk of psychosis onset peaks within 2 years121, it can increase in the longer term at least until 3–4 years40,122,123. In addition, non-transitioning CHR-P individuals can continue to experience functional impairment and symptomatology at 6-years97. This confirms that a 2-year service provision is insufficient21. As such, we recommend clinical monitoring for outcomes to be implemented for at least 3 years (Table 4). Flexible follow-up after this timepoint can help make more efficient use of clinical resources, while tailoring interventions to users’ needs124. For example, the clinical follow-up can be extended if service users are still symptomatic or present socio-occupational difficulties55,62. Finally, CHR-P services should be prepared to collect information and target outcomes other than psychosis such as recovery, physical health outcomes, service users’ satisfaction, functioning, and quality of life20,124. Harmonisation of core outcome set for CHR-P services is a clinical research priority for the future. Several national and regional networks of CHR-P services started to emerge during the decade of 2010–2019 (e.g., EUGEI, PRONIA, PSYSCAN, NAPLS, PNC, HARMONY, PRONET, and STEP) and may facilitate this enterprise, allowing services to leverage best practices and expertise, increasing lobby capacity and enhancing collaborative efforts38,44,46. International clinical research infrastructures have also been developed such as the European College of Neuropsychopharmacology Network for the Prevention of Mental Disorders and Mental Health Promotion (ECNP PMD-MHP)19. These initiatives will introduce several innovations in the CHR-P field, encompassing personalised prediction of outcomes and individualised interventions, digital screening for improving detection of psychosis risk and enhancement of transdiagnostic research capability within CHR-P services (e.g., preventive interventions for bipolar risk)125.

Limitations

The main limitation of this study is that health service information was scattered across services, and that there are no established standards to measure the core domains. This limited the capacity to quantitatively compare the different services with meta-analyses. Future harmonisation efforts in terms of CHR-P healthcare research would be extremely valuable. The database was nonetheless large and sufficiently powered to analyse different factors including service configuration, outreach strategy and referrals, CHR-P service user characteristics, interventions, and outcomes. Another limitation is the limited knowledge provided about the long-term outcomes. Furthermore, our results are based on data from the literature that has been published. However, some clinical services may be running but not publishing details about service configuration, outreach strategy and referrals, service user characteristics, interventions, and outcomes. At the same time, we hope that our review will stimulate the establishment of a global network of CHR-P services with shared clinical research infrastructures21. Finally, a considerable amount of studies were carried out in relatively small samples, with only 45.5% services39,50,51,52,59,62,68,69,73,75,80,82,87,88,89,90,106,126,127,128 including more than 100 CHR-P individuals.

Conclusions

Health service knowledge summarised by the current study will facilitate translational efforts for implementation of CHR-P services worldwide.