We searched Embase, PsycINFO, and MEDLINE with the terms “at risk mental state”, “clinical high risk”, “ultra high risk”, “clinical staging”, “profiling”, “prediction”, “biomarkers”, and “stigma”. We used no language restrictions. We selected key papers from the identified publications on the basis of topic covered and quality of research.
ReviewDetection and treatment of at-risk mental state for developing a first psychosis: making up the balance
Introduction
In many serious illnesses, such as cancer or cardiovascular disease, early detection and optimum and sustained treatment have led to greatly improved prognosis. Since limited treatment possibilities exist in the late stages of major mental disorders, early detection and treatment in psychiatry have generated a lot of interest, with a great deal of indicative—if not yet conclusive—evidence of value.
The need for care emerges well before traditional diagnoses, such as schizophrenia and bipolar disorder, can be applied.1, 2 Early clinical phenotypes are often subthreshold forms of these late phenotypes blended with prominent comorbid features of non-specific distress, including anxiety and depressive symptoms, substance use, and functional disturbance. Clinical experience and research have shown that patients can be engaged in treatment more easily when distress is prominent but symptoms are not yet so severe that illness insight is lost. With accurate public education and pathways to access to care in novel, stigma-free settings, the fear and confusion that people feel could be overcome.3, 4
Despite the face validity of early intervention and the fact that many people who go on to develop a first episode of psychosis present for care during this subthreshold stage,5, 6, 7 the concept has attracted controversy and caused debate, especially in relation to the treatment of subthreshold psychosis. Operationalised criteria, giving rise to ultra-high-risk,8 clinical high-risk,9 or at-risk mental state (ARMS) status,10 have been developed to identify the state in young individuals (14–35 years) seeking help for their mental health problems. To meet these criteria, one or more of the following three presentations are required: attenuated psychotic symptoms, full-blown psychotic symptoms that are brief (ie, lasting less than a week) and self-limiting, and a substantial decrease in functioning in the context of a genetic risk of a psychotic disorder. To meet the ARMS criteria, as defined in the most recent version of the Comprehensive Assessment of At Risk Mental States,11 people should have sustained low psychosocial functioning or a deterioration in functioning for at least a month in the past year in all three presentations. Belonging to one of these so-called putative prodromal groups—referred to hereafter as ARMS—is associated with an enhanced risk of developing a first psychosis.
In some studies, the presence of basic symptoms (self-experienced subclinical disturbances), as assessed by the Bonn Scale for the Assessment of Basic Symptoms—Prediction List, is an additional inclusion criterion.12
The main concerns highlight the genuine issue of risk versus benefit in relation to early detection, which is relevant in any serious medical illness for which potent treatments with side-effects are available, but the risks of delayed or no treatment are also substantial. These concerns centre on the risk of overtreatment with antipsychotic drugs, but theoretical concerns about stigmatisation and labelling have been added (although few data have been published so far).
Critics also point out that most subthreshold patients do not develop sustained psychosis, and claim that most recover without treatment, which they thus deem unnecessary and not cost effective.13 Although we agree that most patients do not develop sustained psychosis, many have a genuine need for care over an extended period. In this Review, we summarise advances and promising developments in this field, gather available evidence, particularly on these key concerns in this debate, and provide guidelines for a balanced, solution-focused approach.
Section snippets
Epidemiology
Mental illnesses account for a larger proportion of disability in developed countries than do any other group of illnesses, including cancer and heart disease.14, 15 Therefore, economic and health-care costs associated with psychiatric disorders are huge (eg, $300 billion annually in the USA),16 not to mention the degree of suffering that these illnesses induce in patients and their families. According to a 2014 report17 from the Organisation for Economic Co-operation and Development, most
Classification and its discontents
In psychiatry, nosology has been defined by the DSM (and ICD) since the World War 2. It is important for any researcher to realise that the DSM does not take into account any (postulated) cause or process underlying the diagnostic categories. The DSM system now defines diagnostic categories by operational criteria on the basis of the presence of symptoms, without reference to supposed psychological or biological processes associated with the diagnostic categories. Thus, the DSM categories do
Transdiagnostic biomarkers
To create a valid nosology of mental illness, a bottom-up, rather than top-down, approach is also necessary. Although biological (eg, cognitive, genetic, neurophysiological, neuroimaging, blood marker) dysfunctions underlie psychiatric disorders, they are not specific for the DSM diagnostic categories, which have been defined top-down. The biological dysfunctions should be studied transdiagnostically—ie, across psychiatric disorders—without the restrictions of the DSM framework. For example,
Clinical staging and profiling in psychiatry
One of the most important developments in psychiatry has been the importation of the concepts of clinical staging and profiling from general medicine, with the aim of a stratified or personalised approach to treatment. Clinical staging is common in many medical specialties and builds on scientific evidence that disorders evolve with time and stages of disease severity can be discerned, including early clinical phenotypes—notably a subclinical prodromal phase.71 Profiling entails the use of
Treatment in a clinical stepped-care model
In the past several years, evidence-based treatment options for ARMS have been developed. Opponents argue that detection and treatment of ARMS would lead to overtreatment with antipsychotics.13 However, patients with ARMS (even when not recognised or labelled as such) are already overmedicated because they are distressed and impaired when seen by primary care and other physicians.89, 90, 91 For example, in a naturalistic study, 91 21% of those with ARMS had been prescribed antipsychotics by the
Stigma
Published works on stigma in ARMS are few and data are even more scarce. In two papers, theoretical and empirical stigma literature is analysed to assess the potential effects of stigma associated with ARMS.108, 109 Stigma can be divided into self-stigmatisation, which is felt irrespective of help-seeking in mental health care, and stigma due to diagnostic and treatment processes. Self-stigmatisation can occur before help-seeking in patients with ARMS when they develop symptoms—eg, hearing a
Seeking help in low-stigma settings
For young people (aged 12–25 years) with emerging psychiatric symptoms, to recognise what is happening to them and take the step to seek help is difficult.113 Help-seeking might be easier in low-stigma settings such as headspace, where not only young people with severe psychiatric problems seek help but also young people with early and mild-to-moderate problems are encouraged to seek assessment and care—eg, with crises or poor self-esteem.114, 115 Young people or their parents and friends can
Conclusion
On the basis of meta-analyses and reviews, we can conclude that treating ARMS leads to a significant reduction in transition rate to a first psychosis (about 50% within 12 months). The number needed to treat is better than that in several other medical specialties in which preventive treatment has been implemented in clinical practice. Furthermore, individualised risk estimation is feasible, but promising research results need to replicated. Overall, longitudinal studies of biology and clinical
Search strategy and selection criteria
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