Clinical High Risk Controversies and Challenge for the Experts

Clinical High Risk Controversies and Challenge for the Experts At risk mental states, ultra high risk and attenuated psychosis syndrome are terms associated with the rapidly expanding field of clinical high risk (CHR) research and initiatives in clinical care. Much is debated as indicated in the theme introduction by Fusar-Poli1 (this issue). Lee et al2 (this issue) address risk prediction for psychopathology beyond the focus on psychosis. Woods et al3 (this issue) test the hypothesis that CHR categories involve pathological processes that are pleuripotential resulting in risk for various disorders. Findings do not support this hypothesis and support a more narrow prediction for associated psychotic disorders. Fusar-Poli et al4 (this issue) provide evidence for the clinical usefulness of the DSM-5, Section 3 attenuated psychosis syndrome. In this, editorial controversies in the field and challenges to the experts will be summarized. Early detection and intervention is time honored throughout medicine. However, the rapidly growing interest regarding mental disorders has been met with substantial concern and opposition. The primary focus emerged from re-conceptualizing schizophrenia prodromal psychopathology as early disorder manifestations. Viewing attenuated psychosis as a clinical disorder, the question of secondary prevention of psychosis came into play. Follow-up studies revealed a robust prediction of transition to full psychosis, usually schizophrenia.5 Within 3 years or so over a quarter of the CHR cases developed a psychotic disorder. This compares with rates for a 3-year period in individuals undergoing CHR assessment, but not meeting intake criteria, of 2%, and a 3-year general population rate of far less than 1%. CHR is a risk category for psychosis as well as a clinical syndrome where all persons merit clinical care. The few clinical trials have suggested that intervention (usually testing CBT vs treatment as usual) is effective in reducing transition to full psychosis, hence providing face validity for risk detection and effective intervention6 So, what could be controversial? A few issues are: • Pathologizing normal experiences and behaviors. • Stigma associated with risk for schizophrenia. • Conceptualizing CHR individuals who do not develop a psychotic illness as false positive cases. • Treatment with antipsychotic medications may be generalized to CHR with an adverse benefit/risk ratio. • The vast majority of persons with a first psychosis episode are not seen in high cost CHR expert centers. The service cost for a few may not be justified when considering the services needs of the many.7 • CHR mainly comprises persons with anxiety, depression, and personality disorders in which psychotic experiences are common.8 • The high risk for a primary psychotic disorder associated with CHR programs may reflect recruitment strategies at expert centers rather than population-based psychopathology. The above issues merit attention. Each is more complex than this brief response can address. Signs and symptoms of mental disorders are experiences and behaviors also found in the nonill general populations, usually without a point of rarity between the ill and non-ill. Recognizing mental illness depends on effects of the experiences and behaviors. Associated with distress, dysfunction and/or disability, the psychotic-like experiences are viewed as symptoms. This is the usual barrier to pathologizing normal behavior and applies to CHR. Self-stigma and social stigma is likely with many of the behaviors associated with CHR. Good clinicians do not label, but rather become informed, develop understanding, relate to problems and aspects of psychopathology, and share a view and understanding with each individual including diagnostic information and what it may mean. Reducing stigma should be a part of ethical and effective clinical care. Indeed, disclosure of a CHR diagnosis may lead to a reduction of psychological distress and increased feelings of control over one’s health.9 The false positive criticism is ill-informed. A CHR diagnosis makes explicit that the course, outcome, and eventual diagnosis, if any, will emerge over time. But clinical care is already indicated. Secondary prevention of psychosis will be relevant for some, but clinical care is applicable for all. The false positive criticism is based on the incorrect assumption that if an individual does not progress to full psychosis it is a mistake to assign the person to CHR. Paradoxically, this view would include persons where prevention of psychosis was successful as “false positives.” Antipsychotic drug use in patients where risk is greater than benefit is already a problem with high utilization across diagnoses and including troubled but not ill young people. The majority of prescriptions are not for persons with a psychotic disorder. A study of vignettes with and without a CHR category found that clinicians were most likely to conclude a full psychotic disorder and recommended AP medication if a category for CHR was not included.10 CHR category with related clinical trials may help guide therapeutic selection and potentially decrease excessive prescribing. The opportunity to establish evidence-based treatment is advanced with a CHR organizing concept. Informing the broad mental health clinical community as well as primary care clinicians regarding therapeutics requires a conceptual framework for communication. For the minority who are progressing to full psychosis the duration of untreated psychosis is expected to be greatly shortened. It is not yet known how effectively the CHR concept can be applied in service systems and cost effectiveness is not known. It is crucial to determine whether advantages associated with expert centers can generalize to systems. This will depend, in part, on clinical assessments that are not dependent on time-consuming structured assessments. The majority of people at CHR appear not to be on a path to psychotic disorders although data to date involves cohorts in clinical care and natural course of CHR is not yet known. An interesting debate is unfolding between the view that CHR mainly captures anxiety and depressive disorders for which we already have diagnostic classes. And that attenuated psychotic features are common in these disorders and full psychosis may simply represent severity of an anxiety or depressive disorder. The alternative view is that CHR as a diagnostic category is heterogeneous and includes individuals that will be identified over time with specific disorders or recovered. But CHR, unlike anxiety and depressive disorders, includes individuals on a path to schizophrenia or other psychotic disorder. The simultaneous manifestation of affective and psychotic symptoms does not establish affective pathology as causative of psychosis. Regardless of causal direction, clinical responsibility will be to address the various psychopathology domains manifest by each patient. This could be done in the context of existing diagnostic categories with the problem of frequent change in diagnosis over time for categories where stability is expected. Or it could be addressed in an explicit place-holder category with the expectation that the diagnosis will be clarified overtime. To gain traction as a category the following challenges need to be addressed. 1. Associated factors including laboratory and imaging measures need to distinguish CHR from nonill controls, but more importantly from clinical help seeking controls who do not meet criteria for CHR or who meet other risk syndromes.11 2. Clinical trials need to address all aspects of symptoms and dysfunction and not be overly dependent on secondary prevention of psychosis. 3. Reliability of assessment in ordinary clinical settings is essential to establish a CHR category. 4. Testing alternative hypotheses of affective pathology driving psychotic experience vs CHR selecting for vulnerability for primary psychotic disorders. 5. Evaluation of cost and effectiveness in clinical systems. Reduce duration of untreated psychosis is expected, but is a better outcome achieved? 6. Reduce confusion resulting from different terms and methods. Recognize that assessments with CAARMS and SIPS indentifying ultra-high risk and APS are 2 overlapping approaches to a similar diagnostic outcome. That BLIPS is a different concept and that the genetic risk group is a risk, but not a clinical category. 7. Make explicit that CHR is proposed as a heterogeneous clinical syndrome and critical aspects of psychopathology and function are individualized in a dimensional framework. The category organizes information and conveys the concept but does not replace multiple relevant dimensions that are therapeutic targets. 8. Take advantage of shared data across sites. Beware of different sampling approaches undermining replication studies. 9. Develop implementation in ordinary clinical settings sensitive to cultural factors and workforce issues. Economic analyses will be important. A challenge to the investigators who have moved the CHR concept to its current position: • Develop a consensus on whether CHR is a category and if so, is it distinguishable from current diagnostic categories. Document value for key aspects of psychopathology and function in addition to secondary prevention of psychosis. • Is the “place holder” diagnostic status necessary for addressing heterogeneity at onset of illness? • Generate the reliability data essential for proposing a new diagnostic category. • Make a proposal for DSM-5.1 to move APS from section 3 to main text including data-based modifications. • Conduct clinical trials relevant to the full range of function and psychopathology of CHR. • Keep in mind that “treatment as usual” is a compromised control as it may be quite effective clinically and any observed superiority of an experimental treatment may underestimate robustness of treatment compared to natural course of illness. References 1. Fusar-Poli, this issue. 2. Leeet al.  , this issue. 3. Woodset al.  , this issue. 4. Fusar-Poliet al.  , this issue. 5. Fusar-Poli P, Borgwardt S, Bechdolf Aet al.   The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry . 2013; 70: 107– 120. Google Scholar CrossRef Search ADS PubMed  6. Stafford MR, Jackson H, Mayo-Wilson E, Morrison AP, Kendall T. Early interventions to prevent psychosis: systematic review and meta-analysis. BMJ . 2013; 346: f185. Google Scholar CrossRef Search ADS PubMed  7. Fusar-Poli P, Rutigliano G, Stahl Det al.   Development and validation of a clinically based risk calculator for the transdiagnostic prediction of psychosis. JAMA Psychiatry . 2017; 74: 493– 500. Google Scholar CrossRef Search ADS PubMed  8. van os J, Guloksuz S. A critique of the “ultra-high risk” and “transition” paradigm. World Psychiatry . 2017; 16: 200– 206. Google Scholar CrossRef Search ADS PubMed  9. Blessing A, Studer A, Gross A, Gruss LF, Schneider R, Dammann G. Disclosure of diagnosis in early recognition of psychosis. J Nerv Ment Dis . 2017; 205: 757– 761. Google Scholar CrossRef Search ADS PubMed  10. Jacobs E, Kline E, Schiffman J. Defining treatment as usual for attenuated psychosis syndrome: a survey of community practitioners. Psychiatr Serv . 2012;63: 1252– 1256. 11. Bernardini F, Attademo L, Cleary SDet al.   Risk prediction models in Psychiatry: toward a new frontier for the prevention of mental illness. J Clin Psychiatry . 2017; 78: 572– 583. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Schizophrenia Bulletin Oxford University Press

Clinical High Risk Controversies and Challenge for the Experts

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Abstract

At risk mental states, ultra high risk and attenuated psychosis syndrome are terms associated with the rapidly expanding field of clinical high risk (CHR) research and initiatives in clinical care. Much is debated as indicated in the theme introduction by Fusar-Poli1 (this issue). Lee et al2 (this issue) address risk prediction for psychopathology beyond the focus on psychosis. Woods et al3 (this issue) test the hypothesis that CHR categories involve pathological processes that are pleuripotential resulting in risk for various disorders. Findings do not support this hypothesis and support a more narrow prediction for associated psychotic disorders. Fusar-Poli et al4 (this issue) provide evidence for the clinical usefulness of the DSM-5, Section 3 attenuated psychosis syndrome. In this, editorial controversies in the field and challenges to the experts will be summarized. Early detection and intervention is time honored throughout medicine. However, the rapidly growing interest regarding mental disorders has been met with substantial concern and opposition. The primary focus emerged from re-conceptualizing schizophrenia prodromal psychopathology as early disorder manifestations. Viewing attenuated psychosis as a clinical disorder, the question of secondary prevention of psychosis came into play. Follow-up studies revealed a robust prediction of transition to full psychosis, usually schizophrenia.5 Within 3 years or so over a quarter of the CHR cases developed a psychotic disorder. This compares with rates for a 3-year period in individuals undergoing CHR assessment, but not meeting intake criteria, of 2%, and a 3-year general population rate of far less than 1%. CHR is a risk category for psychosis as well as a clinical syndrome where all persons merit clinical care. The few clinical trials have suggested that intervention (usually testing CBT vs treatment as usual) is effective in reducing transition to full psychosis, hence providing face validity for risk detection and effective intervention6 So, what could be controversial? A few issues are: • Pathologizing normal experiences and behaviors. • Stigma associated with risk for schizophrenia. • Conceptualizing CHR individuals who do not develop a psychotic illness as false positive cases. • Treatment with antipsychotic medications may be generalized to CHR with an adverse benefit/risk ratio. • The vast majority of persons with a first psychosis episode are not seen in high cost CHR expert centers. The service cost for a few may not be justified when considering the services needs of the many.7 • CHR mainly comprises persons with anxiety, depression, and personality disorders in which psychotic experiences are common.8 • The high risk for a primary psychotic disorder associated with CHR programs may reflect recruitment strategies at expert centers rather than population-based psychopathology. The above issues merit attention. Each is more complex than this brief response can address. Signs and symptoms of mental disorders are experiences and behaviors also found in the nonill general populations, usually without a point of rarity between the ill and non-ill. Recognizing mental illness depends on effects of the experiences and behaviors. Associated with distress, dysfunction and/or disability, the psychotic-like experiences are viewed as symptoms. This is the usual barrier to pathologizing normal behavior and applies to CHR. Self-stigma and social stigma is likely with many of the behaviors associated with CHR. Good clinicians do not label, but rather become informed, develop understanding, relate to problems and aspects of psychopathology, and share a view and understanding with each individual including diagnostic information and what it may mean. Reducing stigma should be a part of ethical and effective clinical care. Indeed, disclosure of a CHR diagnosis may lead to a reduction of psychological distress and increased feelings of control over one’s health.9 The false positive criticism is ill-informed. A CHR diagnosis makes explicit that the course, outcome, and eventual diagnosis, if any, will emerge over time. But clinical care is already indicated. Secondary prevention of psychosis will be relevant for some, but clinical care is applicable for all. The false positive criticism is based on the incorrect assumption that if an individual does not progress to full psychosis it is a mistake to assign the person to CHR. Paradoxically, this view would include persons where prevention of psychosis was successful as “false positives.” Antipsychotic drug use in patients where risk is greater than benefit is already a problem with high utilization across diagnoses and including troubled but not ill young people. The majority of prescriptions are not for persons with a psychotic disorder. A study of vignettes with and without a CHR category found that clinicians were most likely to conclude a full psychotic disorder and recommended AP medication if a category for CHR was not included.10 CHR category with related clinical trials may help guide therapeutic selection and potentially decrease excessive prescribing. The opportunity to establish evidence-based treatment is advanced with a CHR organizing concept. Informing the broad mental health clinical community as well as primary care clinicians regarding therapeutics requires a conceptual framework for communication. For the minority who are progressing to full psychosis the duration of untreated psychosis is expected to be greatly shortened. It is not yet known how effectively the CHR concept can be applied in service systems and cost effectiveness is not known. It is crucial to determine whether advantages associated with expert centers can generalize to systems. This will depend, in part, on clinical assessments that are not dependent on time-consuming structured assessments. The majority of people at CHR appear not to be on a path to psychotic disorders although data to date involves cohorts in clinical care and natural course of CHR is not yet known. An interesting debate is unfolding between the view that CHR mainly captures anxiety and depressive disorders for which we already have diagnostic classes. And that attenuated psychotic features are common in these disorders and full psychosis may simply represent severity of an anxiety or depressive disorder. The alternative view is that CHR as a diagnostic category is heterogeneous and includes individuals that will be identified over time with specific disorders or recovered. But CHR, unlike anxiety and depressive disorders, includes individuals on a path to schizophrenia or other psychotic disorder. The simultaneous manifestation of affective and psychotic symptoms does not establish affective pathology as causative of psychosis. Regardless of causal direction, clinical responsibility will be to address the various psychopathology domains manifest by each patient. This could be done in the context of existing diagnostic categories with the problem of frequent change in diagnosis over time for categories where stability is expected. Or it could be addressed in an explicit place-holder category with the expectation that the diagnosis will be clarified overtime. To gain traction as a category the following challenges need to be addressed. 1. Associated factors including laboratory and imaging measures need to distinguish CHR from nonill controls, but more importantly from clinical help seeking controls who do not meet criteria for CHR or who meet other risk syndromes.11 2. Clinical trials need to address all aspects of symptoms and dysfunction and not be overly dependent on secondary prevention of psychosis. 3. Reliability of assessment in ordinary clinical settings is essential to establish a CHR category. 4. Testing alternative hypotheses of affective pathology driving psychotic experience vs CHR selecting for vulnerability for primary psychotic disorders. 5. Evaluation of cost and effectiveness in clinical systems. Reduce duration of untreated psychosis is expected, but is a better outcome achieved? 6. Reduce confusion resulting from different terms and methods. Recognize that assessments with CAARMS and SIPS indentifying ultra-high risk and APS are 2 overlapping approaches to a similar diagnostic outcome. That BLIPS is a different concept and that the genetic risk group is a risk, but not a clinical category. 7. Make explicit that CHR is proposed as a heterogeneous clinical syndrome and critical aspects of psychopathology and function are individualized in a dimensional framework. The category organizes information and conveys the concept but does not replace multiple relevant dimensions that are therapeutic targets. 8. Take advantage of shared data across sites. Beware of different sampling approaches undermining replication studies. 9. Develop implementation in ordinary clinical settings sensitive to cultural factors and workforce issues. Economic analyses will be important. A challenge to the investigators who have moved the CHR concept to its current position: • Develop a consensus on whether CHR is a category and if so, is it distinguishable from current diagnostic categories. Document value for key aspects of psychopathology and function in addition to secondary prevention of psychosis. • Is the “place holder” diagnostic status necessary for addressing heterogeneity at onset of illness? • Generate the reliability data essential for proposing a new diagnostic category. • Make a proposal for DSM-5.1 to move APS from section 3 to main text including data-based modifications. • Conduct clinical trials relevant to the full range of function and psychopathology of CHR. • Keep in mind that “treatment as usual” is a compromised control as it may be quite effective clinically and any observed superiority of an experimental treatment may underestimate robustness of treatment compared to natural course of illness. References 1. Fusar-Poli, this issue. 2. Leeet al.  , this issue. 3. Woodset al.  , this issue. 4. Fusar-Poliet al.  , this issue. 5. Fusar-Poli P, Borgwardt S, Bechdolf Aet al.   The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry . 2013; 70: 107– 120. Google Scholar CrossRef Search ADS PubMed  6. Stafford MR, Jackson H, Mayo-Wilson E, Morrison AP, Kendall T. Early interventions to prevent psychosis: systematic review and meta-analysis. BMJ . 2013; 346: f185. Google Scholar CrossRef Search ADS PubMed  7. Fusar-Poli P, Rutigliano G, Stahl Det al.   Development and validation of a clinically based risk calculator for the transdiagnostic prediction of psychosis. JAMA Psychiatry . 2017; 74: 493– 500. Google Scholar CrossRef Search ADS PubMed  8. van os J, Guloksuz S. A critique of the “ultra-high risk” and “transition” paradigm. World Psychiatry . 2017; 16: 200– 206. Google Scholar CrossRef Search ADS PubMed  9. Blessing A, Studer A, Gross A, Gruss LF, Schneider R, Dammann G. Disclosure of diagnosis in early recognition of psychosis. J Nerv Ment Dis . 2017; 205: 757– 761. Google Scholar CrossRef Search ADS PubMed  10. Jacobs E, Kline E, Schiffman J. Defining treatment as usual for attenuated psychosis syndrome: a survey of community practitioners. Psychiatr Serv . 2012;63: 1252– 1256. 11. Bernardini F, Attademo L, Cleary SDet al.   Risk prediction models in Psychiatry: toward a new frontier for the prevention of mental illness. J Clin Psychiatry . 2017; 78: 572– 583. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com

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Schizophrenia BulletinOxford University Press

Published: Mar 1, 2018

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