Treatment engagement of individuals experiencing mental illness: review and update

Individuals living with serious mental illness are often difficult to engage in ongoing treatment, with high dropout rates. Poor engagement may lead to worse clinical outcomes, with symptom relapse and rehospitalization. Numerous variables may affect level of treatment engagement, including therapeutic alliance, accessibility of care, and a client's trust that the treatment will address his/her own unique goals. As such, we have found that the concept of recovery‐oriented care, which prioritizes autonomy, empowerment and respect for the person receiving services, is a helpful framework in which to view tools and techniques to enhance treatment engagement. Specifically, person‐centered care, including shared decision making, is a treatment approach that focuses on an individual's unique goals and life circumstances. Use of person‐centered care in mental health treatment models has promising outcomes for engagement. Particular populations of people have historically been difficult to engage, such as young adults experiencing a first episode of psychosis, individuals with coexisting psychotic and substance use disorders, and those who are homeless. We review these populations and outline how various evidence‐based, recovery‐oriented treatment techniques have been shown to enhance engagement. Our review then turns to emerging treatment strategies that may improve engagement. We focus on use of electronics and Internet, involvement of peer providers in mental health treatment, and incorporation of the Cultural Formulation Interview to provide culturally competent, person‐centered care. Treatment engagement is complex and multifaceted, but optimizing recovery‐oriented skills and attitudes is essential in delivery of services to those with serious mental illness.     

Association of preceding psychosis risk states and non‐psychotic mental disorders with incidence of clinical psychosis in the general population: a prospective study in the NEMESIS‐2 cohort

The validity and clinical utility of the concept of “clinical high risk” (CHR) for psychosis have so far been investigated only in risk‐enriched samples in clinical settings. In this population‐based prospective study, we aimed – for the first time – to assess the incidence rate of clinical psychosis and es­timate the population attributable fraction (PAF) of that incidence for preceding psychosis risk states and DSM‐IV diagnoses of non‐psychotic mental disorders (mood disorders, anxiety disorders, alcohol use disorders, and drug use disorders). All analyses were adjusted for age, gender and education. The incidence rate of clinical psychosis was 63.0 per 100,000 person‐years. The mutually‐adjusted Cox proportional hazards model indicated that preceding diagnoses of mood disorders (hazard ratio, HR=10.67, 95% CI: 3.12‐36.49), psychosis high‐risk state (HR=7.86, 95% CI: 2.76‐22.42) and drug use disorders (HR=5.33, 95% CI: 1.61‐17.64) were associated with an increased risk for clinical psychosis incidence. Of the clinical psychosis incidence in the population, 85.5% (95% CI: 64.6‐94.1) was attributable to prior psychopathology, with mood disorders (PAF=66.2, 95% CI: 33.4‐82.9), psychosis high‐risk state (PAF=36.9, 95% CI: 11.3‐55.1), and drug use disorders (PAF=18.7, 95% CI: –0.9 to 34.6) as the most important factors. Although the psychosis high‐risk state displayed a high relative risk for clinical psychosis outcome even after adjusting for other psychopathology, the PAF was comparatively low, given the low prevalence of psychosis high‐risk states in the population. These findings provide empirical evidence for the “prevention paradox” of targeted CHR early intervention. A comprehensive prevention strategy with a focus on broader psychopathology may be more effective than the current psychosis‐focused approach for achieving population‐based improvements in prevention of psychotic disorders.     

Ethical,Legal, and Clinical Considerations when Disclosing a High‐Risk Syndrome for Psychosis

There are complex considerations when planning to disclose an attenuated psychosis syndrome (APS) diagnosis. In this review, we evaluate ethical, legal, and clinical perspectives as well as caveats related to full, non‐ and partial disclosure strategies, discuss societal implications, and provide clinical suggestions. Each of the disclosure strategies is associated with benefits as well as costs/considerations. Full disclosure promotes autonomy, allows for the clearest psychoeducation about additional risk factors, helps to clarify and/or correct previous diagnoses/treatments, facilitates early intervention and bolsters communication between providers but there are important considerations involving heritability, comorbidity, culture, and stigma. Non‐disclosure advances nonmaleficence by limiting stigma and stress (which may inadvertently exacerbate the condition), and confusion (related to the rapidly evolving diagnosis) in a sensitive developmental period but is complicated by varying patient preferences and the possibility that, as new treatments without adverse effects become available, the risk with false positives no longer justifies the accompanying loss of autonomy. Partial disclosure balances ethical considerations by focusing on symptoms instead of labels, but evidence that laypersons may interpret this information as a pseudo‐diagnosis and that symptoms alone also contribute to stigma limits the efficacy of this approach. In addition, there are notable societal considerations relating to disclosure involving conservatorship, the reach of insurance companies, and discrimination. We advocate a hybrid approach to disclosure and recommend future research aimed at understanding the effects of stigma on clinical course and a renewed focus on those help‐seeking cases that do not transition but remain clinically relevant.     

Preventive psychiatry: a blueprint for improving the mental health of young people

Preventive approaches have latterly gained traction for improving mental health in young people. In this paper, we first appraise the conceptual foundations of preventive psychiatry, encompassing the public health, Gordon''s, US Institute of Medicine, World Health Organization, and good mental health frameworks, and neurodevelopmentally‐sensitive clinical staging models. We then review the evidence supporting primary prevention of psychotic, bipolar and common mental disorders and promotion of good mental health as potential transformative strategies to reduce the incidence of these disorders in young people. Within indicated approaches, the clinical high‐risk for psychosis paradigm has received the most empirical validation, while clinical high‐risk states for bipolar and common mental disorders are increasingly becoming a focus of attention. Selective approaches have mostly targeted familial vulnerability and non‐genetic risk exposures. Selective screening and psychological/psychoeducational interventions in vulnerable subgroups may improve anxiety/depressive symptoms, but their efficacy in reducing the incidence of psychotic/bipolar/common mental disorders is unproven. Selective physical exercise may reduce the incidence of anxiety disorders. Universal psychological/psychoeducational interventions may improve anxiety symptoms but not prevent depressive/anxiety disorders, while universal physical exercise may reduce the incidence of anxiety disorders. Universal public health approaches targeting school climate or social determinants (demographic, economic, neighbourhood, environmental, social/cultural) of mental disorders hold the greatest potential for reducing the risk profile of the population as a whole. The approach to promotion of good mental health is currently fragmented. We leverage the knowledge gained from the review to develop a blueprint for future research and practice of preventive psychiatry in young people: integrating universal and targeted frameworks; advancing multivariable, transdiagnostic, multi‐endpoint epidemiological knowledge; synergically preventing common and infrequent mental disorders; preventing physical and mental health burden together; implementing stratified/personalized prognosis; establishing evidence‐based preventive interventions; developing an ethical framework, improving prevention through education/training; consolidating the cost‐effectiveness of preventive psychiatry; and decreasing inequalities. These goals can only be achieved through an urgent individual, societal, and global level response, which promotes a vigorous collaboration across scientific, health care, societal and governmental sectors for implementing preventive psychiatry, as much is at stake for young people with or at risk for emerging mental disorders.     

Early intervention in psychosis: concepts,evidence and future directions

The rise of the early intervention paradigm in psychotic disorders represents a maturing of the therapeutic approach in psychiatry, as it embraces practical preventive strategies which are firmly established in mainstream health care. Early intervention means better access and systematic early delivery of existing and incremental improvements in knowledge rather than necessarily requiring dramatic and elusive breakthroughs. A clinical staging model has proven useful and may have wider utility in psychiatry. The earliest clinical stages of psychotic disorder are non-specific and multidimensional and overlap phenotypically with the initial stages of other disorders. This implies that treatment should proceed in a stepwise fashion depending upon safety, response and progression. Withholding treatment until severe and less reversible symptomatic and functional impairment have become entrenched represents a failure of care. While early intervention in psychosis has developed strongly in recent years, many countries have made no progress at all, and others have achieved only sparse coverage. The reform process has been substantially evidence-based, arguably more so than other system reforms in mental health. However, while evidence is necessary, it is insufficient. It is also a by-product as well as a catalyst of reform. In early psychosis, we have also seen the evidence-based paradigm misused to frustrate overdue reform. Mental disorders are the chronic diseases of the young, with their onset and maximum impact in late adolescence and early adult life. A broader focus for early intervention would solve many of the second order issues raised by the early psychosis reform process, such as diagnostic uncertainty despite a clear-cut need for care, stigma and engagement, and should be more effective in mobilizing community support. Early intervention represents a vital and challenging project for early adopters in global psychiatry to consider.     

Bioökonomie und der Mensch

Bio‐economy and human being A widely accepted vision is a prerequisite for an effective prevention and successful overcoming of inevitable acceptance problems during the implementation process of a bio‐economy strategy. The best biotech / bio‐economic innovation can not be implemented in a welfare enhancing way, if the following conditions are not met: 1) innovation‐related, normative issues have to be already discussed at the societal level before or during the development of innovations, 2) the associated risks and opportunities are identified and communicated and 3) strategies to avoid these risks are developed. All this requires participation of the affected societal groups along with effective communication strategies.     

Ultra high risk status and transition to psychosis in 22q11.2 deletion syndrome

The 22q11.2 deletion syndrome (22q11DS) is characterized by high rates of psychotic symptoms and schizophrenia, making this condition a promising human model for studying risk factors for psychosis. We explored the predictive value of ultra high risk (UHR) criteria in a sample of patients with 22q11DS. We also examined the additional contribution of socio‐demographic, clinical and cognitive variables to predict transition to psychosis within a mean interval of 32.5 ± 17.6 months after initial assessment. Eighty‐nine participants with 22q11DS (age range: 8‐30 years; mean 16.1 ± 4.7) were assessed using the Structured Interview for Psychosis‐Risk Syndromes. Information on Axis I diagnoses, internalizing and externalizing symptoms, level of functioning and IQ was also collected. At baseline, 22 (24.7%) participants met UHR criteria. Compared to those without a UHR condition, they had a significantly lower functioning, more frequent anxiety disorders, and more severe psychopathology. Transition rate to psychosis was 27.3% in UHR and 4.5% in non‐UHR participants. Cox regression analyses revealed that UHR status significantly predicted conversion to psychosis. Baseline level of functioning was the only other additional predictor. This is the first study investigating the predictive value of UHR criteria in 22q11DS. It indicates that the clinical path leading to psychosis is broadly comparable to that observed in other clinical high‐risk samples. Nevertheless, the relatively high transition rate in non‐UHR individuals suggests that other risk markers should be explored in this population. The role of low functioning as a predictor of transition to psychosis should also be investigated more in depth.     

Prediction of psychosis across protocols and risk cohorts using automated language analysis

Language and speech are the primary source of data for psychiatrists to diagnose and treat mental disorders. In psychosis, the very structure of language can be disturbed, including semantic coherence (e.g., derailment and tangentiality) and syntactic complexity (e.g., concreteness). Subtle disturbances in language are evident in schizophrenia even prior to first psychosis onset, during prodromal stages. Using computer‐based natural language processing analyses, we previously showed that, among English‐speaking clinical (e.g., ultra) high‐risk youths, baseline reduction in semantic coherence (the flow of meaning in speech) and in syntactic complexity could predict subsequent psychosis onset with high accuracy. Herein, we aimed to cross‐validate these automated linguistic analytic methods in a second larger risk cohort, also English‐speaking, and to discriminate speech in psychosis from normal speech. We identified an automated machine‐learning speech classifier – comprising decreased semantic coherence, greater variance in that coherence, and reduced usage of possessive pronouns – that had an 83% accuracy in predicting psychosis onset (intra‐protocol), a cross‐validated accuracy of 79% of psychosis onset prediction in the original risk cohort (cross‐protocol), and a 72% accuracy in discriminating the speech of recent‐onset psychosis patients from that of healthy individuals. The classifier was highly correlated with previously identified manual linguistic predictors. Our findings support the utility and validity of automated natural language processing methods to characterize disturbances in semantics and syntax across stages of psychotic disorder. The next steps will be to apply these methods in larger risk cohorts to further test reproducibility, also in languages other than English, and identify sources of variability. This technology has the potential to improve prediction of psychosis outcome among at‐risk youths and identify linguistic targets for remediation and preventive intervention. More broadly, automated linguistic analysis can be a powerful tool for diagnosis and treatment across neuropsychiatry.     

Beyond the “at risk mental state” concept: transitioning to transdiagnostic psychiatry

The “at risk mental state” for psychosis approach has been a catalytic, highly productive research paradigm over the last 25 years. In this paper we review that paradigm and summarize its key lessons, which include the valence of this phenotype for future psychosis outcomes, but also for comorbid, persistent or incident non‐psychotic disorders; and the evidence that onset of psychotic disorder can at least be delayed in ultra high risk (UHR) patients, and that some full‐threshold psychotic disorder may emerge from risk states not captured by UHR criteria. The paradigm has also illuminated risk factors and mechanisms involved in psychosis onset. However, findings from this and related paradigms indicate the need to develop new identification and diagnostic strategies. These findings include the high prevalence and impact of mental disorders in young people, the limitations of current diagnostic systems and risk identification approaches, the diffuse and unstable symptom patterns in early stages, and their pluripotent, transdiagnostic trajectories. The approach we have recently adopted has been guided by the clinical staging model and adapts the original “at risk mental state” approach to encompass a broader range of inputs and output target syndromes. This approach is supported by a number of novel modelling and prediction strategies that acknowledge and reflect the dynamic nature of psychopathology, such as dynamical systems theory, network theory, and joint modelling. Importantly, a broader transdiagnostic approach and enhancing specific prediction (profiling or increasing precision) can be achieved concurrently. A holistic strategy can be developed that applies these new prediction approaches, as well as machine learning and iterative probabilistic multimodal models, to a blend of subjective psychological data, physical disturbances (e.g., EEG measures) and biomarkers (e.g., neuroinflammation, neural network abnormalities) acquired through fine‐grained sequential or longitudinal assessments. This strategy could ultimately enhance our understanding and ability to predict the onset, early course and evolution of mental ill health, further opening pathways for preventive interventions.     

Predictors of type 2 diabetes in a nationally representative sample of adults with psychosis

Antipsychotic drugs such as clozapine and olanzapine are associated with an increased risk for type 2 diabetes, but relatively little is known about the relationship between risk factors for type 2 diabetes established in the general population and type 2 diabetes in people with psychosis. We estimated the prevalence of established risk factors and their association with type 2 diabetes in a nationally representative sample of people with an ICD‐10 psychosis (N=1642) who gave a fasting blood sample (N=1155). Logistic regression was used to summarize associations adjusted for age and sex. In this sample, whose mean duration of psychosis was 14.7 years, 12.1% (13.1% of women and 11.5% of men) had type 2 diabetes at age 18–64 years based on current fasting blood glucose levels or treatment with a hypoglycaemic drug. Risk was greatly increased in young adults compared with the general population and peaked in middle age. Risk factors in the general population were common in people with psychosis and strongly associated with type 2 diabetes in those people. Treatment with clozapine was associated with an increased risk and treatment with olanzapine with a decreased risk for type 2 diabetes. The development of diabetes or pre‐diabetes may therefore influence the likelihood of treatment with olanzapine over time. The strongest predictors of type 2 diabetes in a multivariate model were a body mass index of at least 40 and treated hypercholesterolemia, followed by a body mass index between 35 and 39.9, a family history of diabetes and treated hypertension. There was minimal to no confounding of the association between type 2 diabetes and current clozapine or olanzapine treatment, but neither association remained significant after adjustment for other predictors. Longitudinal relationships among predictors are likely to be complex, and previous antipsychotic drug treatment may at least partly explain risks associated with severe obesity, dyslipidemia and hypertension. A focus on weight loss is warranted in people with psychosis, but prevention strategies for type 2 diabetes should be broadened to include those with emerging dyslipidemia, hypertension and a family history of diabetes.     

Transdiagnostic risk of mental disorders in offspring of affected parents: a meta-analysis of family high-risk and registry studies

The offspring of parents with mental disorders are at increased risk for developing mental disorders themselves. The risk to offspring may extend transdiagnostically to disorders other than those present in the parents. The literature on this topic is vast but mixed. To inform targeted prevention and genetic counseling, we performed a comprehensive, PRISMA 2020-compliant meta-analysis. We systematically searched the literature published up to September 2022 to retrieve original family high-risk and registry studies reporting on the risk of mental disorders in offspring of parents with any type of mental disorder. We performed random-effects meta-analyses of the relative risk (risk ratio, RR) and absolute risk (lifetime, up to the age at assessment) of mental disorders, defined according to the ICD or DSM. Cumulative incidence by offspring age was determined using meta-analytic Kaplan-Meier curves. We measured heterogeneity with the I² statistic, and risk of bias with the Quality In Prognosis Studies (QUIPS) tool. Sensitivity analyses addressed the impact of study design (family high-risk vs. registry) and specific vs. transdiagnostic risks. Transdiagnosticity was appraised with the TRANSD criteria. We identified 211 independent studies that reported data on 3,172,115 offspring of parents with psychotic, bipolar, depressive, disruptive, attention-deficit/hyperactivity, anxiety, substance use, eating, obsessive-compulsive, and borderline personality disorders, and 20,428,575 control offspring. The RR and lifetime risk of developing any mental disorder were 3.0 and 55% in offspring of parents with anxiety disorders; 2.6 and 17% in offspring of those with psychosis; 2.1 and 55% in offspring of those with bipolar disorder; 1.9 and 51% in offspring of those with depressive disorders; and 1.5 and 38% in offspring of those with substance use disorders. The offspring's RR and lifetime risk of developing the same mental disorder diagnosed in their parent were 8.4 and 32% for attention-deficit/hyperactivity disorder; 5.8 and 8% for psychosis; 5.1 and 5% for bipolar disorder; 2.8 and 9% for substance use disorders; 2.3 and 14% for depressive disorders; 2.3 and 1% for eating disorders; and 2.2 and 31% for anxiety disorders. There were 37 significant transdiagnostic associations between parental mental disorders and the RR of developing a different mental disorder in the offspring. In offspring of parents with psychosis, bipolar and depressive disorder, the risk of the same disorder onset emerged at 16, 5 and 6 years, and cumulated to 3%, 19% and 24% by age 18; and to 8%, 36% and 46% by age 28. Heterogeneity ranged from 0 to 0.98, and 96% of studies were at high risk of bias. Sensitivity analyses restricted to prospective family high-risk studies confirmed the pattern of findings with similar RR, but with greater absolute risks compared to analyses of all study types. This study demonstrates at a global, meta-analytic level that offspring of affected parents have strongly elevated RR and lifetime risk of developing any mental disorder as well as the same mental disorder diagnosed in the parent. The transdiagnostic risks suggest that offspring of parents with a range of mental disorders should be considered as candidates for targeted primary prevention.     

A critique of the “ultra‐high risk” and “transition” paradigm

The transdiagnostic expression of psychotic experiences in common mental disorder (anxiety/depression/substance use disorder) is associated with a poorer prognosis, and a small minority of people may indeed develop a clinical picture that meets criteria for schizophrenia. However, it appears neither useful nor valid to observe early states of multidimensional psychopathology in young people through the “schizo”‐prism, and apply misleadingly simple, unnecessary and inefficient binary concepts of “risk” and “transition”. A review of the “ultra‐high risk” (UHR) or “clinical high risk” (CHR) literature indicates that UHR/CHR samples are highly heterogeneous and represent individuals diagnosed with common mental disorder (anxiety/depression/substance use disorder) and a degree of psychotic experiences. Epidemiological research has shown that psychotic experiences are a (possibly non‐causal) marker of the severity of multidimensional psychopathology, driving poor outcome, yet notions of “risk” and “transition” in UHR/CHR research are restrictively defined on the basis of positive psychotic phenomena alone, ignoring how baseline differences in multidimensional psychopathology may differentially impact course and outcome. The concepts of “risk” and “transition” in UHR/CHR research are measured on the same dimensional scale, yet are used to produce artificial diagnostic shifts. In fact, “transition” in UHR/CHR research occurs mainly as a function of variable sample enrichment strategies rather than the UHR/CHR “criteria” themselves. Furthermore, transition rates in UHR/CHR research are inflated as they do not exclude false positives associated with the natural fluctuation of dimensional expression of psychosis. Biological associations with “transition” thus likely represent false positive findings, as was the initial claim of strong effects of omega‐3 polyunsatured fatty acids in UHR samples. A large body of UHR/CHR intervention research has focused on the questionable outcome of “transition”, which shows lack of correlation with functional outcome. It may be more productive to consider the full range of person‐specific psychopathology in all young individuals who seek help for mental health problems, instead of “policing” youngsters for the transdiagnostic dimension of psychosis. Instead of the relatively inefficient medical high‐risk approach, a public health perspective, focusing on improved access to a low‐stigma, high‐hope, small scale and youth‐specific environment with acceptable language and interventions may represent a more useful and efficient strategy.     

Psychosis as a transdiagnostic and extended phenotype in the general population

A large body of research indicates that weak expressions of positive psychotic symptoms (“psychotic experiences”) can be measured in the general population, and likely represent the behavioural manifestation of distributed multifactorial (genetic and non‐genetic) risk for psychosis. Psychotic experiences are a transdiagnostic phenomenon: the majority of individuals with these experiences have a diagnosis of non‐psychotic disorder, particularly common mental disorder, in which psychotic experiences predict greater illness severity and poorer treatment response. Some of the people with common mental disorder and psychotic experiences will present to mental health services meeting criteria for “clinical high risk”. Treatment of the transdiagnostic dimension of psychosis in individuals with common mental disorder who meet “clinical high risk” criteria thus may improve outcome (which cannot be interpreted as prevention of “schizophrenia”). Subthreshold psychotic experiences are transitory in about 80% of individuals, while around 20% go on to develop persistent psychotic experiences and 7% a psychotic disorder, with an annual transition rate of 0.5‐1%. Persistence is associated, on the one hand, with environmental exposures, particularly childhood trauma, and, on the other, with network‐type dynamic interactions between psychotic experiences themselves (e.g., interactions between hallucinatory experiences and delusional ideation) and between symptom dimensions (e.g., interactions between affective symptoms and psychotic experiences, or interactions between subthreshold negative symptoms and psychotic experiences). The study of psychotic experiences is helping to elucidate the mechanisms by which environmental and genetic influences shape the transdiagnostic expression of psychosis proneness, that is mostly transitory but may first become persistent over time and eventually give rise to transition to a psychotic disorder.     

Comparing three‐year extension of early intervention service to regular care following two years of early intervention service in first‐episode psychosis: a randomized single blind clinical trial

This study aimed to determine if, following two years of early intervention service for first‐episode psychosis, three‐year extension of that service was superior to three years of regular care. We conducted a randomized single blind clinical trial using an urn randomization balanced for gender and substance abuse. Participants were recruited from early intervention service clinics in Montreal. Patients (N=220), 18‐35 years old, were randomized to an extension of early intervention service (EEIS; N=110) or to regular care (N=110). EEIS included case management, family intervention, cognitive behaviour therapy and crisis intervention, while regular care involved transfer to primary (community health and social services and family physicians) or secondary care (psychiatric outpatient clinics). Cumulative length of positive and negative symptom remission was the primary outcome measure. EEIS patients had a significantly longer mean length of remission of positive symptoms (92.5 vs. 63.6 weeks, t=4.47, p<0.001), negative symptoms (73.4 vs. 59.6 weeks, t=2.84, p=0.005) and both positive and negative symptoms (66.5 vs. 56.7 weeks, t=2.25, p=0.03) compared to regular care patients. EEIS patients stayed in treatment longer than regular care patients (mean 131.7 vs. 105.3 weeks, t=3.98, p<0.001 through contact with physicians; 134.8 ± 37.7 vs. 89.8 ± 55.2, t=6.45, p<0.0001 through contact with other health care providers) and received more units of treatment (mean 74.9 vs. 39.9, t=4.21, p<0.001 from physicians, and 57.3 vs. 28.2, t=4.08, p<0.001 from other health care professionals). Length of treatment had an independent effect on the length of remission of positive symptoms (t=2.62, p=0.009), while number of units of treatment by any health care provider had an effect on length of remission of negative symptoms (t=?2.70, p=0.008) as well as total symptoms (t=?2.40, p=0.02). Post‐hoc analysis showed that patients randomized to primary care, based on their better clinical profile at randomization, maintained their better outcome, especially as to remission of negative symptoms, at the end of the study. These data suggest that extending early intervention service for three additional years has a positive impact on length of remission of positive and negative symptoms compared to regular care. This may have policy implications for extending early intervention services beyond the current two years.     

Economics and mental health: the current scenario

Economics and mental health are intertwined. Apart from the accumulating evidence of the huge economic impacts of mental ill‐health, and the growing recognition of the effects that economic circumstances can exert on mental health, governments and other budget‐holders are putting increasing emphasis on economic data to support their decisions. Here we consider how economic evaluation (including cost‐effectiveness analysis, cost‐utility analysis and related techniques) can contribute evidence to inform the development of mental health policy strategies, and to identify some consequences at the treatment or care level that are of relevance to service providers and funding bodies. We provide an update and reflection on economic evidence relating to mental health using a lifespan perspective, analyzing costs and outcomes to shed light on a range of pressing issues. The past 30 years have witnessed a rapid growth in mental health economics, but major knowledge gaps remain. Across the lifespan, clearer evidence exists in the areas of perinatal depression identification‐plus‐treatment; risk‐reduction of mental health problems in childhood and adolescence; scaling up treatment, particularly psychotherapy, for depression; community‐based early intervention and employment support for psychosis; and cognitive stimulation and multicomponent carer interventions for dementia. From this discussion, we pull out the main challenges that are faced when trying to take evidence from research and translating it into policy or practice recommendations, and from there to actual implementation in terms of better treatment and care.     

At risk or not at risk? A meta‐analysis of the prognostic accuracy of psychometric interviews for psychosis prediction

An accurate detection of individuals at clinical high risk (CHR) for psychosis is a prerequisite for effective preventive interventions. Several psychometric interviews are available, but their prognostic accuracy is unknown. We conducted a prognostic accuracy meta‐analysis of psychometric interviews used to examine referrals to high risk services. The index test was an established CHR psychometric instrument used to identify subjects with and without CHR (CHR+ and CHR?). The reference index was psychosis onset over time in both CHR+ and CHR? subjects. Data were analyzed with MIDAS (STATA13). Area under the curve (AUC), summary receiver operating characteristic curves, quality assessment, likelihood ratios, Fagan's nomogram and probability modified plots were computed. Eleven independent studies were included, with a total of 2,519 help‐seeking, predominately adult subjects (CHR+: N=1,359; CHR?: N=1,160) referred to high risk services. The mean follow‐up duration was 38 months. The AUC was excellent (0.90; 95% CI: 0.87‐0.93), and comparable to other tests in preventive medicine, suggesting clinical utility in subjects referred to high risk services. Meta‐regression analyses revealed an effect for exposure to antipsychotics and no effects for type of instrument, age, gender, follow‐up time, sample size, quality assessment, proportion of CHR+ subjects in the total sample. Fagan's nomogram indicated a low positive predictive value (5.74%) in the general non‐help‐seeking population. Albeit the clear need to further improve prediction of psychosis, these findings support the use of psychometric prognostic interviews for CHR as clinical tools for an indicated prevention in subjects seeking help at high risk services worldwide.     

The clinical characterization of the patient with primary psychosis aimed at personalization of management

The current management of patients with primary psychosis worldwide is often remarkably stereotyped. In almost all cases an antipsychotic medica­tion is prescribed, with second‐generation antipsychotics usually preferred to first‐generation ones. Cognitive behavioral therapy is rarely used in the vast majority of countries, although there is evidence to support its efficacy. Psychosocial interventions are often provided, especially in chronic cases, but those applied are frequently not validated by research. Evidence‐based family interventions and supported employment programs are seldom implemented in ordinary practice. Although the notion that patients with primary psychosis are at increased risk for cardiovascular diseases and diabetes mellitus is widely shared, it is not frequent that appropriate measures be implemented to address this problem. The view that the management of the patient with primary psychosis should be personalized is endorsed by the vast majority of clinicians, but this personalization is lacking or inadequate in most clinical contexts. Although many mental health services would declare themselves “recovery‐oriented”, it is not common that a focus on empowerment, identity, meaning and resilience is ensured in ordinary practice. The present paper aims to address this situation. It describes systematically the salient domains that should be considered in the characterization of the individual patient with primary psychosis aimed at personalization of management. These include positive and negative symptom dimensions, other psychopathological components, onset and course, neurocognition and social cognition, neurodevelopmental indicators; social functioning, quality of life and unmet needs; clinical staging, antecedent and concomitant psychiatric conditions, physical comorbidities, family history, history of obstetric complications, early and recent environmental exposures, protective factors and resilience, and internalized stigma. For each domain, simple assessment instruments are identified that could be considered for use in clinical practice and included in standardized decision tools. A management of primary psychosis is encouraged which takes into account all the available treatment modalities whose efficacy is supported by research evidence, selects and modulates them in the individual patient on the basis of the clinical characterization, addresses the patient’s needs in terms of employment, housing, self‐care, social relationships and education, and offers a focus on identity, meaning and resilience.     

Lack of evidence to favor specific preventive interventions in psychosis: a network meta‐analysis

Preventing psychosis in patients at clinical high risk may be a promising avenue for pre‐emptively ameliorating outcomes of the most severe psychiatric disorder. However, information on how each preventive intervention fares against other currently available treatment options remains unavailable. The aim of the current study was to quantify the consistency and magnitude of effects of specific preventive interventions for psychosis, comparing different treatments in a network meta‐analysis. PsycINFO, Web of Science, Cochrane Central Register of Controlled Trials, and unpublished/grey literature were searched up to July 18, 2017, to identify randomized controlled trials conducted in individuals at clinical high risk for psychosis, comparing different types of intervention and reporting transition to psychosis. Two reviewers independently extracted data. Data were synthesized using network meta‐analyses. The primary outcome was transition to psychosis at different time points and the secondary outcome was treatment acceptability (dropout due to any cause). Effect sizes were reported as odds ratios and 95% confidence intervals (CIs). Sixteen studies (2,035 patients, 57% male, mean age 20.1 years) reported on risk of transition. The treatments tested were needs‐based interventions (NBI); omega‐3 + NBI; ziprasidone + NBI; olanzapine + NBI; aripiprazole + NBI; integrated psychological interventions; family therapy + NBI; D‐serine + NBI; cognitive behavioural therapy, French & Morrison protocol (CBT‐F) + NBI; CBT‐F + risperidone + NBI; and cognitive behavioural therapy, van der Gaag protocol (CBT‐V) + CBT‐F + NBI. The network meta‐analysis showed no evidence of significantly superior efficacy of any one intervention over the others at 6 and 12 months (insufficient data were available after 12 months). Similarly, there was no evidence for intervention differences in acceptability at either time point. Tests for inconsistency were non‐significant and sensitivity analyses controlling for different clustering of interventions and biases did not materially affect the interpretation of the results. In summary, this study indicates that, to date, there is no evidence that any specific intervention is particularly effective over the others in preventing transition to psychosis. Further experimental research is needed.     

Prediction and prevention of schizophrenia: what has been achieved and where to go next?

In modern medicine, vigorous efforts are being made in the prediction and prevention of diseases. Mental disorders are suitable candidates for the application of this program. The currently known neurobiological and psychosocial risk indicators for schizophrenia do not have a predictive power sufficient for selective prevention in asymptomatic patients at risk. However, once predictive basic and later pre-psychotic high risk symptoms of psychosis develop into the five-year initial prodrome, the impending outbreak of the disease can be predicted with high accuracy. Research findings suggest a differential strategy of indicated prevention with cognitive behavioral therapy in early initial prodromal states and low dosage atypical antipsychotics in late initial prodromal states. The most important future tasks are the improvement of the predictive power by risk enrichment and stratification, as well as the confirmation of the existing and the development of new prevention strategies, with a stronger focus on the etiology of the disorder. In addition, the prediction and prevention approach would benefit from the inclusion of risk symptoms in the DSM-5 criteria.