TY - JOUR
T1 - Prevention of Psychosis Advances in Detection, Prognosis, and Intervention
AU - Fusar-Poli, Paolo
AU - Salazar de Pablo, Gonzalo
AU - Correll, Christoph U.
AU - Meyer-Lindenberg, Andreas
AU - Millan, Mark J.
AU - Borgwardt, Stefan
AU - Galderisi, Silvana
AU - Bechdolf, Andreas
AU - Pfennig, Andrea
AU - Kessing, Lars Vedel
AU - van Amelsvoort, Therese
AU - Nieman, Dorien H.
AU - Domschke, Katharina
AU - Krebs, Marie-Odile
AU - Koutsouleris, Nikolaos
AU - McGuire, Philip
AU - Do, Kim Q.
AU - Arango, Celso
N1 - Funding Information:
part by the European College of Neuropsychopharmacology Network Taskforce and by the Alicia Koplowitz Foundation (Dr Salazar de Pablo).
Funding Information:
Sunovion, Otsuka, Recordati, Servier, Janssen, and Lundbeck. Dr Galderisi reported receiving personal fees from Millennium Pharmaceuticals, Innova Pharma-Recordati, Janssen Pharmaceutica NV, Sunovion Pharmaceuticals, Janssen-Cilag Polska, Gedeon-Richter-Recordati, Pierre Fabre, Otsuka, and Angelini-Acraf outside the submitted work. Dr Bechdolf reported receiving grants from the German Research Foundation and the German Ministry of Health as well as grants and personal fees from Otsuka, Lundbeck, and Janssen during the conduct of the study. Dr Krebs reported receiving financial support for educational activities or boards from Janssen and Otsuka Lundbeck. Dr Koutsouleris reported receiving honoraria from Otsuka outside the submitted work and holding a patent to US20160192889A1. Dr Do reported receiving grants from the Swiss National Foundation for scientific research during the conduct of the study and grants from Boehringer Ingelheim outside the submitted work. Dr Arango reported receiving personal fees from Acadia, Angelini, Gedeon-Richter, Janssen-Cilag, Lundbeck, Sage, Sanofi, Servier, Shire, Schering-Plough, Sumitomo Dainippon Pharma, Sunovion, and Takeda outside the submitted work as well as nonfinancial support from Roche. No other disclosures were reported.
Funding Information:
reported receiving grants and personal fees from Lundbeck and personal fees from Menarini outside the submitted work. Dr Salazar de Pablo reported receiving grants from Fundacion Alicia Koplowitz during the conduct of the study. Dr Correll reported receiving personal fees from Alkermes, Allergan, Angelini, Boehringer-Ingelheim, Gedeon Richter, Gerson Lehrman Group, Indivior, IntraCellular Therapies, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Merck, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, and Teva outside the submitted work; grants and personal fees from Janssen/Johnson & Johnson and Takeda; and royalties from UpToDate as well as being a shareholder of LB Pharma. Dr Meyer-Lindenberg reported receiving support or grants from the Ministry of Science, Research and the Arts of the State of Baden-Wuerttemberg, Germany; the European Union’s Seventh Framework Programme; the Innovative Medicines Initiative Joint Undertaking; the German Federal Ministry of Education and Research; and the German Research Foundation. Dr Millan reported being a full-time employee of Institut de Recherche Servier. Dr Borgwardt reported receiving support from the University of Basel, the European Union’s Seventh Framework Programme, the Swiss National Science Foundation, and the European Research Area Net and educational funds from
Publisher Copyright:
© 2020 American Medical Association. All rights reserved.
PY - 2020/7
Y1 - 2020/7
N2 - Importance Detection, prognosis, and indicated interventions in individuals at clinical high risk for psychosis (CHR-P) are key components of preventive psychiatry. Objective To provide a comprehensive, evidence-based systematic appraisal of the advancements and limitations of detection, prognosis, and interventions for CHR-P individuals and to formulate updated recommendations. Evidence Review Web of Science, Cochrane Central Register of Reviews, and Ovid/PsychINFO were searched for articles published from January 1, 2013, to June 30, 2019, to identify meta-analyses conducted in CHR-P individuals. MEDLINE was used to search the reference lists of retrieved articles. Data obtained from each article included first author, year of publication, topic investigated, type of publication, study design and number, sample size of CHR-P population and comparison group, type of comparison group, age and sex of CHR-P individuals, type of prognostic assessment, interventions, quality assessment (using AMSTAR [Assessing the Methodological Quality of Systematic Reviews]), and key findings with their effect sizes. Findings In total, 42 meta-analyses published in the past 6 years and encompassing 81 outcomes were included. For the detection component, CHR-P individuals were young (mean [SD] age, 20.6 [3.2] years), were more frequently male (58%), and predominantly presented with attenuated psychotic symptoms lasting for more than 1 year before their presentation at specialized services. CHR-P individuals accumulated several sociodemographic risk factors compared with control participants. Substance use (33% tobacco use and 27% cannabis use), comorbid mental disorders (41% with depressive disorders and 15% with anxiety disorders), suicidal ideation (66%), and self-harm (49%) were also frequently seen in CHR-P individuals. CHR-P individuals showed impairments in work (Cohen d = 0.57) or educational functioning (Cohen d = 0.21), social functioning (Cohen d = 1.25), and quality of life (Cohen d = 1.75). Several neurobiological and neurocognitive alterations were confirmed in this study. For the prognosis component, the prognostic accuracy of CHR-P instruments was good, provided they were used in clinical samples. Overall, risk of psychosis was 22% at 3 years, and the risk was the highest in the brief and limited intermittent psychotic symptoms subgroup (38%). Baseline severity of attenuated psychotic (Cohen d = 0.35) and negative symptoms (Cohen d = 0.39) as well as low functioning (Cohen d = 0.29) were associated with an increased risk of psychosis. Controlling risk enrichment and implementing sequential risk assessments can optimize prognostic accuracy. For the intervention component, no robust evidence yet exists to favor any indicated intervention over another (including needs-based interventions and control conditions) for preventing psychosis or ameliorating any other outcome in CHR-P individuals. However, because the uncertainty of this evidence is high, needs-based and psychological interventions should still be offered. Conclusions and Relevance This review confirmed recent substantial advancements in the detection and prognosis of CHR-P individuals while suggesting that effective indicated interventions need to be identified. This evidence suggests a need for specialized services to detect CHR-P individuals in primary and secondary care settings, to formulate a prognosis with validated psychometric instruments, and to offer needs-based and psychological interventions.Question What is the status of current clinical knowledge in the detection, prognosis, and interventions for individuals at risk of psychosis? Findings In this review of 42 meta-analyses encompassing 81 outcomes, detecting individuals at risk for psychosis required knowledge of their specific sociodemographic, clinical, functional, cognitive, and neurobiological characteristics, and predicting outcomes was achieved with good accuracy provided that assessment tools were used in clinical samples. Evidence for specific effective interventions for this patient population is currently insufficient. Meaning Findings of this review suggest that, although clinical research knowledge for psychosis prevention is substantial and detecting and formulating a prognosis in individuals at risk for psychosis are possible, further research is needed to identify specific effective interventions in individuals with sufficient risk enrichment.This review synthesizes research findings from 42 meta-analyses that assessed detection, prognosis, and interventions for the prevention of psychosis and offers updated practice recommendations.
AB - Importance Detection, prognosis, and indicated interventions in individuals at clinical high risk for psychosis (CHR-P) are key components of preventive psychiatry. Objective To provide a comprehensive, evidence-based systematic appraisal of the advancements and limitations of detection, prognosis, and interventions for CHR-P individuals and to formulate updated recommendations. Evidence Review Web of Science, Cochrane Central Register of Reviews, and Ovid/PsychINFO were searched for articles published from January 1, 2013, to June 30, 2019, to identify meta-analyses conducted in CHR-P individuals. MEDLINE was used to search the reference lists of retrieved articles. Data obtained from each article included first author, year of publication, topic investigated, type of publication, study design and number, sample size of CHR-P population and comparison group, type of comparison group, age and sex of CHR-P individuals, type of prognostic assessment, interventions, quality assessment (using AMSTAR [Assessing the Methodological Quality of Systematic Reviews]), and key findings with their effect sizes. Findings In total, 42 meta-analyses published in the past 6 years and encompassing 81 outcomes were included. For the detection component, CHR-P individuals were young (mean [SD] age, 20.6 [3.2] years), were more frequently male (58%), and predominantly presented with attenuated psychotic symptoms lasting for more than 1 year before their presentation at specialized services. CHR-P individuals accumulated several sociodemographic risk factors compared with control participants. Substance use (33% tobacco use and 27% cannabis use), comorbid mental disorders (41% with depressive disorders and 15% with anxiety disorders), suicidal ideation (66%), and self-harm (49%) were also frequently seen in CHR-P individuals. CHR-P individuals showed impairments in work (Cohen d = 0.57) or educational functioning (Cohen d = 0.21), social functioning (Cohen d = 1.25), and quality of life (Cohen d = 1.75). Several neurobiological and neurocognitive alterations were confirmed in this study. For the prognosis component, the prognostic accuracy of CHR-P instruments was good, provided they were used in clinical samples. Overall, risk of psychosis was 22% at 3 years, and the risk was the highest in the brief and limited intermittent psychotic symptoms subgroup (38%). Baseline severity of attenuated psychotic (Cohen d = 0.35) and negative symptoms (Cohen d = 0.39) as well as low functioning (Cohen d = 0.29) were associated with an increased risk of psychosis. Controlling risk enrichment and implementing sequential risk assessments can optimize prognostic accuracy. For the intervention component, no robust evidence yet exists to favor any indicated intervention over another (including needs-based interventions and control conditions) for preventing psychosis or ameliorating any other outcome in CHR-P individuals. However, because the uncertainty of this evidence is high, needs-based and psychological interventions should still be offered. Conclusions and Relevance This review confirmed recent substantial advancements in the detection and prognosis of CHR-P individuals while suggesting that effective indicated interventions need to be identified. This evidence suggests a need for specialized services to detect CHR-P individuals in primary and secondary care settings, to formulate a prognosis with validated psychometric instruments, and to offer needs-based and psychological interventions.Question What is the status of current clinical knowledge in the detection, prognosis, and interventions for individuals at risk of psychosis? Findings In this review of 42 meta-analyses encompassing 81 outcomes, detecting individuals at risk for psychosis required knowledge of their specific sociodemographic, clinical, functional, cognitive, and neurobiological characteristics, and predicting outcomes was achieved with good accuracy provided that assessment tools were used in clinical samples. Evidence for specific effective interventions for this patient population is currently insufficient. Meaning Findings of this review suggest that, although clinical research knowledge for psychosis prevention is substantial and detecting and formulating a prognosis in individuals at risk for psychosis are possible, further research is needed to identify specific effective interventions in individuals with sufficient risk enrichment.This review synthesizes research findings from 42 meta-analyses that assessed detection, prognosis, and interventions for the prevention of psychosis and offers updated practice recommendations.
KW - CLINICAL HIGH-RISK
KW - ULTRA-HIGH RISK
KW - 1ST-EPISODE PSYCHOSIS
KW - COMPREHENSIVE ASSESSMENT
KW - COGNITIVE DEFICITS
KW - MENTAL STATE
KW - CANNABIS USE
KW - INDIVIDUALS
KW - METAANALYSIS
KW - ONSET
U2 - 10.1001/jamapsychiatry.2019.4779
DO - 10.1001/jamapsychiatry.2019.4779
M3 - (Systematic) Review article
C2 - 32159746
SN - 2168-622X
VL - 77
SP - 755
EP - 765
JO - JAMA Psychiatry
JF - JAMA Psychiatry
IS - 7
ER -