Improving outcomes of first-episode psychosis: an overview

Paolo Fusar-Poli, Patrick D McGorry, John M Kane, Paolo Fusar-Poli, Patrick D McGorry, John M Kane

Abstract

Outcomes of psychotic disorders are associated with high personal, familiar, societal and clinical burden. There is thus an urgent clinical and societal need for improving those outcomes. Recent advances in research knowledge have opened new opportunities for ameliorating outcomes of psychosis during its early clinical stages. This paper critically reviews these opportunities, summarizing the state-of-the-art knowledge and focusing on recent discoveries and future avenues for first episode research and clinical interventions. Candidate targets for primary universal prevention of psychosis at the population level are discussed. Potentials offered by primary selective prevention in asymptomatic subgroups (stage 0) are presented. Achievements of primary selected prevention in individuals at clinical high risk for psychosis (stage 1) are summarized, along with challenges and limitations of its implementation in clinical practice. Early intervention and secondary prevention strategies at the time of a first episode of psychosis (stage 2) are critically discussed, with a particular focus on minimizing the duration of untreated psychosis, improving treatment response, increasing patients' satisfaction with treatment, reducing illicit substance abuse and preventing relapses. Early intervention and tertiary prevention strategies at the time of an incomplete recovery (stage 3) are further discussed, in particular with respect to addressing treatment resistance, improving well-being and social skills with reduction of burden on the family, treatment of comorbid substance use, and prevention of multiple relapses and disease progression. In conclusion, to improve outcomes of a complex, heterogeneous syndrome such as psychosis, it is necessary to globally adopt complex models integrating a clinical staging framework and coordinated specialty care programmes that offer pre-emptive interventions to high-risk groups identified across the early stages of the disorder. Only a systematic implementation of these models of care in the national health care systems will render these strategies accessible to the 23 million people worldwide suffering from the most severe psychiatric disorders.

Keywords: Psychosis; clinical high risk; clinical staging; first episode psychosis; indicated prevention; outcomes; psychosis risk; schizophrenia; selective prevention; universal prevention.

© 2017 World Psychiatric Association.

Figures

Figure 1
Figure 1
Meta‐analytical odds for relapses (hospital readmission) with specialized integrated early intervention services (EI) compared to standard care (TAU) in the community. Odds ratios smaller than 1 indicate an association of reduced relapses with EI, while odds ratios greater than 1 indicate an association of reduced relapses with TAU. Weights are from random effects analysis.

References

    1. Global Burden of Disease Study 2013 Collaborators . Global, regional, and national incidence, prevalence, and years lived with dis ability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015;386:743‐800.
    1. World Health Organization . Schizophrenia. .
    1. Jaaskelainen E, Juola P, Hirvonen N et al. A systematic review and meta‐analysis of recovery in schizophrenia. Schizophr Bull 2013;39:1296‐306.
    1. Millan MJ, Andrieux A, Bartzokis G et al. Altering the course of schizophrenia: progress and perspectives. Nat Rev Drug Discov 2016;5:485‐51.
    1. Chong HY, Teoh SL, Wu DB et al. Global economic burden of schizophrenia: a systematic review. Neuropsychiatr Dis Treat 2016;12:357‐73.
    1. Walker ER, McGee RE, Druss BG. Mortality in mental disorders and global disease burden implications: a systematic review and meta‐analysis. JAMA Psychiatry 2015;72:334‐41.
    1. McGlashan TH. Early detection and intervention of schizophrenia: rationale and research. Br J Psychiatry 1998;172(Suppl. 33):3‐6.
    1. Birchwood M, Todd P, Jackson C. Early intervention in psychosis. The critical period hypothesis. Br J Psychiatry 1998;172(Suppl. 33):53‐9.
    1. McGorry PD, Hickie IB, Yung AR et al. Clinical staging of psychiatric disorders: a heuristic framework for choosing earlier, safer and more effective interventions. Aust N Z J Psychiatry 2006;40:616‐22.
    1. Gordon R. An operational classification of disease prevention. Publ Health Rep 1983;98:107‐9.
    1. World Health Organization. Prevention of mental disorders. Effective interventions and policy options. Geneva: World Health Organization, 2004.
    1. Millan MJ, Andrieux A, Bartzokis G et al. Altering the course of schizophrenia: progress and perspectives. Nat Rev Drug Discov 2016;15:485‐515.
    1. Ross RG, Hunter SK, McCarthy L et al. Perinatal choline effects on neonatal pathophysiology related to later schizophrenia risk. Am J Psychiatry 2013;170:290‐8.
    1. Waasdorp TE, Bradshaw CP, Leaf PJ. The impact of schoolwide positive behavioral interventions and supports on bullying and peer rejection: a randomized controlled effectiveness trial. Arch Pediatr Adolesc Med 2012;166:149‐56.
    1. Nocentini A, Menesini E. KiVa Anti‐Bullying Program in Italy: evidence of effectiveness in a randomized control trial. Prev Sci 2016;17:1012‐23.
    1. Jenkins DD, Wiest DB, Mulvihill DM et al. Fetal and neonatal effects of N‐acetylcysteine when used for neuroprotection in maternal chorioamnionitis. J Pediatr 2016;168:67‐76.
    1. Pusceddu MM, Kelly P, Stanton C et al. N‐3 Polyunsaturated fatty acids through the lifespan: implication for psychopathology. Int J Neuropsychopharmacol (in press).
    1. Dawson SL, Bowe SJ, Crowe TC. A combination of omega‐3 fatty acids, folic acid and B‐group vitamins is superior at lowering homocysteine than omega‐3 alone: a meta‐analysis. Nutr Res 2016;36:499‐508.
    1. Kurtys E, Eisel UL, Verkuyl JM et al. The combination of vitamins and omega‐3 fatty acids has an enhanced anti‐inflammatory effect on microglia. Neurochem Int 2016;99:206‐14.
    1. Do KQ, Cuenod M, Hensch TK. Targeting oxidative stress and aberrant critical period plasticity in the developmental trajectory to schizophrenia. Schizophr Bull 2015;41:835‐46.
    1. Fond G, Boukouaci W, Chevalier G et al. The “psychomicrobiotic”: targeting microbiota in major psychiatric disorders: a systematic review. Pathol Biol 2015;63:35‐42.
    1. Patnode CD, O'Connor E, Rowland M et al. Primary care behavioral interventions to prevent or reduce illicit drug use and nonmedical pharmaceutical use in children and adolescents: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2014;160:612‐20.
    1. Vogl LE, Newton NC, Champion KE et al. A universal harm‐minimisation approach to preventing psychostimulant and cannabis use in adolescents: a cluster randomised controlled trial. Subst Abuse Treat Prev Policy 2014;9:24.
    1. Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci 2002;25:295‐301.
    1. Draganski B, Gaser C, Busch V et al. Neuroplasticity: changes in grey matter induced by training. Nature 2004;427:311‐2.
    1. Douw L, Nieboer D, van Dijk BW et al. A healthy brain in a healthy body: brain network correlates of physical and mental fitness. PLoS One 2014;9:e88202.
    1. Lee TM, Wong ML, Lau BW et al. Aerobic exercise interacts with neurotrophic factors to predict cognitive functioning in adolescents. Psychoneuroendocrinology 2014;39:214‐24.
    1. Fusar‐Poli P, Tantardini M, De Simone S et al. Deconstructing vulnerability for psychosis: meta‐analysis of environmental risk factors for psychosis in subjects at ultra high‐risk. Eur Psychiatry 2016;40:65‐75.
    1. Rasic D, Hajek T, Alda M et al. Risk of mental illness in offspring of parents with schizophrenia, bipolar disorder, and major depressive disorder: a meta‐analysis of family high‐risk studies. Schizophr Bull 2014;40:28‐38.
    1. Torrey EF, Buka S, Cannon TD et al. Paternal age as a risk factor for schizophrenia: how important is it? Schizophr Res 2009;114:1‐5.
    1. Cannon M, Jones PB, Murray RM. Obstetric complications and schizophrenia: historical and meta‐analytic review. Am J Psychiatry 2002;159:1080‐92.
    1. Geddes JR, Verdoux H, Takei N et al. Schizophrenia and complications of pregnancy and labor: an individual patient data meta‐analysis. Schizophr Bull 1999;25:413‐23.
    1. Cai L, Wan CL, He L et al. Gestational influenza increases the risk of psychosis in adults. Med Chem 2015;11:676‐82.
    1. Davies G, Welham J, Chant D et al. A systematic review and meta‐analysis of Northern Hemisphere season of birth studies in schizophrenia. Schizophr Bull 2003;29:587‐93.
    1. Bosqui TJ, Hoy K, Shannon C. A systematic review and meta‐analysis of the ethnic density effect in psychotic disorders. Soc Psychiatry Psychiatr Epidemiol 2014;49:519‐29.
    1. Tortelli A, Errazuriz A, Croudace T et al. Schizophrenia and other psychotic disorders in Caribbean‐born migrants and their descendants in England: systematic review and meta‐analysis of incidence rates, 1950–2013. Soc Psychiatry Psychiatr Epidemiol 2015;50:1039‐55.
    1. Kirkbride JB, Errazuriz A, Croudace TJ et al. Incidence of schizophrenia and other psychoses in England, 1950–2009: a systematic review and meta‐analyses. PLoS One 2012;7:e31660.
    1. Bourque F, van der Ven E, Malla A. A meta‐analysis of the risk for psychotic disorders among first‐ and second‐generation immigrants. Psychol Med 2011;41:897‐910.
    1. Vassos E, Pedersen CB, Murray RM et al. Meta‐analysis of the association of urbanicity with schizophrenia. Schizophr Bull 2012;38:1118‐23.
    1. Khandaker GM, Zimbron J, Dalman C et al. Childhood infection and adult schizophrenia: a meta‐analysis of population‐based studies. Schizophr Res 2012;139:161‐8.
    1. Arias I, Sorlozano A, Villegas E et al. Infectious agents associated with schizophrenia: a meta‐analysis. Schizophr Res 2012;136:128‐36.
    1. Sutterland AL, Fond G, Kuin A et al. Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta‐analysis. Acta Psychiatr Scand 2015;132:161‐79.
    1. Molloy C, Conroy RM, Cotter DR et al. Is traumatic brain injury a risk factor for schizophrenia? A meta‐analysis of case‐controlled population‐based studies. Schizophr Bull 2011;37:1104‐10.
    1. Valipour G, Saneei P, Esmaillzadeh A. Serum vitamin D levels in relation to schizophrenia: a systematic review and meta‐analysis of observational studies. J Clin Endocrinol Metab 2014;99:3863‐72.
    1. Gurillo P, Jauhar S, Murray RM et al. Does tobacco use cause psychosis? Systematic review and meta‐analysis. Lancet Psychiatry 2015;2:718‐25.
    1. Marconi A, Di Forti M, Lewis CM et al. Meta‐analysis of the association between the level of cannabis use and risk of psychosis. Schizophr Bull 2016;42:1262‐9.
    1. Varese F, Smeets F, Drukker M et al. Childhood adversities increase the risk of psychosis: a meta‐analysis of patient‐control, prospective‐ and cross‐sectional cohort studies. Schizophr Bull 2012;38:661‐71.
    1. Beards S, Gayer‐Anderson C, Borges S et al. Life events and psychosis: a review and meta‐analysis. Schizophr Bull 2013;39:740‐7.
    1. Woodberry KA, Giuliano AJ, Seidman LJ. Premorbid IQ in schizophrenia: a meta‐analytic review. Am J Psychiatry 2008;165:579‐87.
    1. Khandaker GM, Barnett JH, White IR et al. A quantitative meta‐analysis of population‐based studies of premorbid intelligence and schizophrenia. Schizophr Res 2011;132:220‐7.
    1. Seidman LJ, Nordentoft M. New targets for prevention of schizophrenia: is it time for interventions in the premorbid phase? Schizophr Bull 2015;41:795‐800.
    1. Fusar‐Poli P, Cappucciati M, Rutigliano G et al. At risk or not at risk? Meta‐analysis of the prognostic accuracy of psychometric interviews for psychosis prediction. World Psychiatry 2015;14:322‐32.
    1. Fusar‐Poli P, Cappucciati M, Rutigliano G et al. Towards a standard psychometric diagnostic interview for subjects at ultra high risk of psychosis: CAARMS versus SIPS. Psychiatry J 2016:7146341.
    1. Fusar‐Poli P, Schultze‐Lutter F. Predicting the onset of psychosis in patients at clinical high risk: practical guide to probabilistic prognostic reasoning. Evidence‐Based Mental Health 2016;19:10‐5.
    1. Yung AR, McGorry PD, McFarlane CA et al. Monitoring and care of young people at incipient risk of psychosis. Schizophr Bull 1996;22:283‐303.
    1. Fusar‐Poli P, Borgwardt S, Bechdolf A et al. The psychosis high‐risk state: a comprehensive state‐of‐the‐art review. JAMA Psychiatry 2013;70:107‐20.
    1. Fusar‐Poli P, Rocchetti M, Sardella A et al. Disorder, not just a state of risk: meta‐analysis of functioning and quality of life in subjects at high clinical risk for psychosis. Br J Psychiatry 2015;207:198‐206.
    1. Fusar‐Poli P, Cappucciati M, Borgwardt S et al. Heterogeneity of risk for psychosis within subjects at clinical high risk: meta‐analytical stratification. JAMA Psychiatry 2016;73:113‐20.
    1. Kempton M, Bonoldi I, Valmaggia L et al. Speed of psychosis progression in people at ultra high clinical risk: a complementary meta‐analysis. JAMA Psychiatry 2015;72:622‐3.
    1. Fusar‐Poli P, Rutigliano G, Stahl D et al. Long‐term validity of the at risk mental state (ARMS) for predicting psychotic and non‐psychotic mental disorders. Eur Psychiatry 2017;42:49‐54.
    1. Webb JR, Addington J, Perkins DO et al. Specificity of incident diagnostic outcomes in patients at clinical high risk for psychosis. Schizophr Bull 2015;41:1066‐75.
    1. Simon AE, Borgwardt S, Riecher‐Rössler A et al. Moving beyond transition outcomes: meta‐analysis of remission rates in individuals at high clinical risk for psychosis. Psychiatry Res 2013;209:266‐72.
    1. Fusar‐Poli P, Nelson B, Valmaggia L et al. Comorbid depressive and anxiety disorders in 509 individuals with an at‐risk mental state: impact on psychopathology and transition to psychosis. Schizophr Bull 2014;40:120‐31.
    1. Rutigliano G, Valmaggia L, Landi P et al. Persistence or recurrence of non‐psychotic comorbid mental disorders associated with 6‐year poor functional outcomes in patients at ultra high risk for psychosis. J Affect Disord 2016;203:101‐10.
    1. Lin A, Wood SJ, Nelson B et al. Outcomes of nontransitioned cases in a sample at ultra‐high risk for psychosis. Am J Psychiatry 2015;172:249‐58.
    1. National Health Service England . Mental health access and waiting time standards. London: National Health Service England, 2014.
    1. National Health Service England. Achieving better access to mental health services by 2020. London: National Health Service England, 2014.
    1. Fusar‐Poli P, Carpenter WT, Woods SW et al. Attenuated psychosis syndrome: ready for DSM‐5.1? Annu Rev Clin Psychol 2014;10:155‐92.
    1. National Institute for Health and Care Excellence. Psychosis and schizophrenia in children and young people: recognition and management. .
    1. Nelson B, Yuen HP, Wood SJ et al. Long‐term follow‐up of a group at ultra high risk (“prodromal”) for psychosis: the PACE 400 study. JAMA Psychiatry 2013;70:793‐802.
    1. O'Connell M, Boat T, Warner K. (eds). Preventing mental, emotional, and behavioral disorders among young people: progress and possibilities. Washington: National Academies Press, 2009.
    1. van der Gaag M, Smit F, Bechdolf A et al. Preventing a first episode of psychosis: meta‐analysis of randomized controlled prevention trials of 12 month and longer‐term follow‐ups. Schizophr Res 2013;149:56‐62.
    1. McGorry P, Nelson B, Markulev C et al. Effect of ω‐3 polyunsaturated fatty acids in young people at ultrahigh risk for psychotic disorders. JAMA Psychiatry 2017;74:19‐27.
    1. Morrison AP, French P, Stewart SL et al. Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial. BMJ 2012;344:e2233.
    1. McFarlane WR, Levin B, Travis L et al. Clinical and functional outcomes after 2 years in the early detection and intervention for the prevention of psychosis multisite effectiveness trial. Schizophr Bull 2015;41:30‐43.
    1. Fusar‐Poli P, Byrne M, Badger S et al. Outreach and support in south London (OASIS), 2001–2011: ten years of early diagnosis and treatment for young individuals at high clinical risk for psychosis. Eur Psychiatry 2013;28:315‐26.
    1. Valmaggia LR, Byrne M, Day F et al. Duration of untreated psychosis and need for admission in patients who engage with mental health services in the prodromal phase. Br J Psychiatry 2015;207:130‐4.
    1. Fusar‐Poli P, Diaz‐Caneja CM, Patel R et al. Services for people at high risk improve outcomes in patients with first episode psychosis. Acta Psychiatr Scand 2016;133:76‐85.
    1. Schultze‐Lutter F, Michel C, Schmidt SJ et al. EPA guidance on the early detection of clinical high risk states of psychoses. Eur Psychiatry 2015;30:405‐16.
    1. Fusar‐Poli P, Rutigliano G, Stahl D et al. Development and validation of a clinically based risk calculator for the transdiagnostic prediction of psychosis. JAMA Psychiatry 2017;74:493‐500.
    1. Birchwood M, Connor C, Lester H et al. Reducing duration of untreated psychosis: care pathways to early intervention in psychosis services. Br J Psychiatry 2013;203:58‐64.
    1. Fusar Poli P. Why ultra high risk criteria for psychosis prediction do not work well outside clinical samples and what to do about it. World Psychiatry 2017;16:212‐3.
    1. Fusar‐Poli P, Schultze‐Lutter F, Cappucciati M et al. The dark side of the moon: meta‐analytical impact of recruitment strategies on risk enrichment in the clinical high risk state for psychosis. Schizophr Bull 2016;42:732‐43.
    1. Fusar‐Poli P, Rutigliano G, Stahl D et al. Deconstructing pretest risk enrichment to optimize prediction of psychosis in individuals at clinical high risk. JAMA Psychiatry 2016;73:1260‐7.
    1. Fusar‐Poli P, Schultze‐Lutter F, Addington J. Intensive community outreach for those at ultra high risk of psychosis: dilution, not solution. Lancet Psychiatry 2016;3:18.
    1. Michel C, Schimmelmann BG, Schultze‐Lutter F. What becomes of risk symptoms in the community? 2.5 year follow‐up findings of the Bern Epidemiological At‐Risk (BEAR) Study. Early Interv Psychiatry 2016;10(S1):129.
    1. Schmidt A, Cappucciati M, Radua J et al. Improving prognostic accuracy in subjects at clinical high risk for psychosis: systematic review of predictive models and meta‐analytical sequential testing simulation. Schizophr Bull 2017;43:375‐88.
    1. Calkins M, Moore T, Satterthwaite T et al. Persistence of psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort: a prospective two year follow‐up. World Psychiatry 2017;16:62‐76.
    1. Fusar‐Poli P. The Clinical High‐Risk State for Psychosis (CHR‐P), Version II. Schizophr Bull 2017;43:44‐7.
    1. Fusar‐Poli P, Cappucciati M, Bonoldi I et al. Prognosis of brief psychotic episodes: a meta‐analysis. JAMA Psychiatry 2016;73:211‐20.
    1. Carrion R, Correll C, Auther A et al. A severity‐based clinical staging model for the psychosis prodrome: longitudinal findings from New York RAP study. Schizophr Bull 2017;43:64‐74.
    1. Fusar‐Poli P, Cappucciati M, De Micheli A et al. Diagnostic and prognostic significance of brief limited intermittent psychotic symptoms (BLIPS) in individuals at ultra high risk. Schizophr Bull 2017;43:48‐56.
    1. National Institute for Health and Care Excellence. Bipolar disorder, psychosis and schizophrenia in children and young people. .
    1. Andreasen NC, Carpenter WT Jr, Kane JM et al. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry 2005;162:441‐9.
    1. Wunderink L, Sytema S, Nienhuis FJ et al. Clinical recovery in first‐episode psychosis. Schizophr Bull 2009;35:362‐9.
    1. Penttila M, Jaaskelainen E, Hirvonen N et al. Duration of untreated psychosis as predictor of long‐term outcome in schizophrenia: systematic review and meta‐analysis. Br J Psychiatry 2014;205:88‐94.
    1. Connor C, Birchwood M, Freemantle N et al. Don't turn your back on the symptoms of psychosis: the results of a proof‐of‐principle, quasi‐experimental intervention to reduce duration of untreated psychosis. BMC Psychiatry 2016;16:127.
    1. Craig TK, Garety P, Power P et al. The Lambeth Early Onset (LEO) Team: randomised controlled trial of the effectiveness of specialised care for early psychosis. BMJ 2004;329:1067.
    1. Kuipers E, Holloway F, Rabe‐Hesketh S et al. An RCT of early intervention in psychosis: Croydon Outreach and Assertive Support Team (COAST). Soc Psychiatry Psychiatr Epidemiol 2004;39:358‐63.
    1. Grawe RW, Falloon IR, Widen JH et al. Two years of continued early treatment for recent‐onset schizophrenia: a randomised controlled study. Acta Psychiatr Scand 2006;114:328‐36.
    1. Sigrúnarson V, Grawe RW, Morken G. Integrated treatment vs. treatment‐as‐usual for recent onset schizophrenia; 12 year follow‐up on a randomized controlled trial. BMC Psychiatry 2013;13:200.
    1. Petersen L, Jeppesen P, Thorup A et al. A randomised multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness. BMJ 2005;331:602.
    1. Bertelsen M, Jeppesen P, Petersen L et al. Five‐year follow‐up of a randomized multicenter trial of intensive early intervention vs standard treatment for patients with a first episode of psychotic illness: the OPUS trial. Arch Gen Psychiatry 2008;65:762‐71.
    1. Secher RG, Hjorthoj CR, Austin SF et al. Ten‐year follow‐up of the OPUS specialized early intervention trial for patients with a first episode of psychosis. Schizophr Bull 2015;41:617‐26.
    1. Kane JM, Robinson DG, Schooler NR et al. Comprehensive versus usual community care for first‐episode psychosis: 2‐year outcomes from the NIMH RAISE Early Treatment Program. Am J Psychiatry 2016;173:362‐72.
    1. Ruggeri M, Bonetto C, Lasalvia A et al. Feasibility and effectiveness of a multi‐element psychosocial intervention for first‐episode psychosis: results from the cluster‐randomized controlled GET UP PIANO trial in a catchment area of 10 million inhabitants. Schizophr Bull 2015;41:1192‐203.
    1. Srihari VH, Tek C, Kucukgoncu S et al. First‐episode services for psychotic disorders in the U.S. public sector: a pragmatic randomized controlled trial. Psychiatr Serv 2015;66:705‐12.
    1. Chang WC, Chan GH, Jim OT et al. Optimal duration of an early intervention programme for first‐episode psychosis: randomised controlled trial. Br J Psychiatry 2015;206:492‐500.
    1. Chang WC, Kwong VW, Chan GH et al. Prediction of functional remission in first‐episode psychosis: 12‐month follow‐up of the randomized‐controlled trial on extended early intervention in Hong Kong. Schizophr Res 2016;173:79‐83.
    1. Ando S, Nishida A, Koike S et al. Comprehensive early intervention for patients with first‐episode psychosis in Japan (J‐CAP): nine‐month follow‐up of randomized controlled trial. Early Interv Psychiatry 2016;8(S1):1‐180.
    1. Chien WT, Thompson DR, Lubman DI et al. A randomized controlled trial of clinician‐supported problem‐solving bibliotherapy for family caregivers of people with first‐episode psychosis. Schizophr Bull 2016;42:1457‐66.
    1. Schoeler T, Petros N, Di Forti M et al. Association between continued cannabis use and risk of relapse in first‐episode psychosis: a quasi‐experimental investigation within an observational study. JAMA Psychiatry 2016;73:1173‐9.
    1. Johnson S, Sheridan Rains L, Marwaha S et al. A randomised controlled trial of the clinical and cost‐effectiveness of a contingency management intervention compared to treatment as usual for reduction of cannabis use and of relapse in early psychosis (CIRCLE): a study protocol for a randomised controlled trial. Trials 2016;17:515.
    1. Edwards J, Elkins K, Hinton M et al. Randomized controlled trial of a cannabis‐focused intervention for young people with first‐episode psychosis. Acta Psychiatr Scand 2006;114:109‐17.
    1. Penn DL, Waldheter EJ, Perkins DO et al. Psychosocial treatment for first‐episode psychosis: a research update. Am J Psychiatry 2005;162:2220‐32.
    1. Nordentoft M, Rasmussen JO, Melau M et al. How successful are first episode programs? A review of the evidence for specialized assertive early intervention. Curr Opin Psychiatry 2014;27:167‐72.
    1. Gleeson JF, Alvarez‐Jimenez M, Cotton SM et al. A systematic review of relapse measurement in randomized controlled trials of relapse prevention in first‐episode psychosis. Schizophr Res 2010;119:79‐88.
    1. Alvarez‐Jimenez M, Parker AG, Hetrick SE et al. Preventing the second episode: a systematic review and meta‐analysis of psychosocial and pharmacological trials in first‐episode psychosis. Schizophr Bull 2011;37:619‐30.
    1. Pelayo‐Teran JM, Gajardo Galán VG, de la Ortiz‐ Garcĺa de la Foz V et al. Rates and predictors of relapse in first‐episode non‐affective psychosis: a 3‐year longitudinal study in a specialized intervention program (PAFIP). Eur Arch Psychiatry Clin Neurosci 2017;267:315‐23.
    1. National Institute for Health and Care Excellence. Psychosis and schizophrenia in adults: prevention and management. .
    1. Leucht S, Tardy M, Komossa K et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta‐analysis. Lancet 2012;379:2063‐71.
    1. Correll CU, Citrome L, Haddad PM et al. The use of long‐acting injectable antipsychotics in schizophrenia: evaluating the evidence. J Clin Psychiatry 2016;77(Suppl. 3):1‐24.
    1. Kishi T, Oya K, Iwata N. Long‐acting injectable antipsychotics for the prevention of relapse in patients with recent‐onset psychotic disorders: a systematic review and meta‐analysis of randomized controlled trials. Psychiatry Res 2016;246:750‐5
    1. Ostuzzi G, Bighelli I, So R et al. Does formulation matter? A systematic review and meta‐analysis of oral versus long‐acting antipsychotic studies. Schizophr Res 2017;183:10‐21.
    1. Misawa F, Kishimoto T, Hagi K et al. Safety and tolerability of long‐acting injectable versus oral antipsychotics: a meta‐analysis of randomized controlled studies comparing the same antipsychotics. Schizophr Res 2016;176:220‐30.
    1. Kishi T, Matsunaga S, Iwata N. Mortality risk associated with long‐acting injectable antipsychotics: a systematic review and meta‐analyses of randomized controlled trials. Schizophr Bull 2016;42:1438‐45.
    1. Kishimoto T, Robenzadeh A, Leucht C et al. Long‐acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta‐analysis of randomized trials. Schizophr Bull 2014;40:192‐213.
    1. Fusar‐Poli P, Kempton MJ, Rosenheck RA. Efficacy and safety of second‐generation long‐acting injections in schizophrenia: a meta‐analysis of randomized‐controlled trials. Int Clin Psychopharmacol 2013;28:57‐66.
    1. Haddad PM, Taylor M, Niaz OS. First‐generation antipsychotic long‐acting injections v. oral antipsychotics in schizophrenia: systematic review of randomised controlled trials and observational studies. Br J Psychiatry 2009;195(Suppl. 52):S20‐8.
    1. Kishimoto T, Nitta M, Borenstein M et al. Long‐acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta‐analysis of mirror‐image studies. J Clin Psychiatry 2013;74:957‐65.
    1. Lutgens D, Iyer S, Joober R et al. A five‐year randomized parallel and blinded clinical trial of an extended specialized early intervention vs. regular care in the early phase of psychotic disorders: study protocol. BMC Psychiatry 2015;15:22.
    1. Rosenheck R, Leslie D, Sint K et al. Cost‐effectiveness of comprehensive, integrated care for first episode psychosis in the NIMH RAISE Early Treatment Program. Schizophr Bull 2016;42:896‐906.
    1. Csillag C, Nordentoft M, Mizuno M et al. Early intervention services in psychosis: from evidence to wide implementation. Early Interv Psychiatry 2016;10:540‐6.
    1. Park AL, McCrone P, Knapp M. Early intervention for first‐episode psychosis: broadening the scope of economic estimates. Early Interv Psychiatry 2016;10:144‐51.
    1. Fusar‐Poli P, Cappucciati M, Rutigliano G et al. Diagnostic stability of ICD/DSM first episode psychosis diagnoses: meta‐analysis. Schizophr Bull 2016;42:1395‐406.
    1. Catts SV, O'Toole BI. The treatment of schizophrenia: can we raise the standard of care? Aust N Z J Psychiatry 2016;50:1128‐38.
    1. Chang WC, Lau ES, Chiu SS et al. Three‐year clinical and functional outcome comparison between first‐episode mania with psychotic features and first‐episode schizophrenia. J Affect Disord 2016;200:1‐5.
    1. Friis S, Melle I, Johannessen JO et al. Early predictors of ten‐year course in first‐episode psychosis. Psychiatr Serv 2016;67:438‐43.
    1. Heslin M, Lappin JM, Donoghue K et al. Ten‐year outcomes in first episode psychotic major depression patients compared with schizophrenia and bipolar patients. Schizophr Res 2016;176:417‐22.
    1. Austin SF, Mors O, Budtz‐ Jorgensen E et al. Long‐term trajectories of positive and negative symptoms in first episode psychosis: a 10 year follow‐up study in the OPUS cohort. Schizophr Res 2015;168:84‐91.
    1. Morgan C, Lappin J, Heslin M et al. Reappraising the long‐term course and outcome of psychotic disorders: the AESOP‐10 study. Psychol Med 2014;44:2713‐26.
    1. Dixon LB, Holoshitz Y, Nossel I. Treatment engagement of individuals experiencing mental illness: review and update. World Psychiatry 2016;15:13‐20.
    1. Emsley R, Chiliza B, Asmal L et al. The nature of relapse in schizophrenia. BMC Psychiatry 2013;13:50.
    1. Correll CU, Robinson DG, Schooler NR et al. Cardiometabolic risk in patients with first‐episode schizophrenia spectrum disorders: baseline results from the RAISE‐ETP study. JAMA Psychiatry 2014;71:1350‐63.
    1. Wunderink L, Nieboer RM, Wiersma D et al. Recovery in remitted first‐episode psychosis at 7 years of follow‐up of an early dose reduction/discontinuation or maintenance treatment strategy: long‐term follow‐up of a 2‐year randomized clinical trial. JAMA Psychiatry 2013;70:913‐20.
    1. Murray RM, Quattrone D, Natesan S et al. Should psychiatrists be more cautious about the long‐term prophylactic use of antipsychotics? Br J Psychiatry 2016;209:361‐5.
    1. Takeuchi H, Suzuki T, Uchida H et al. Antipsychotic treatment for schizophrenia in the maintenance phase: a systematic review of the guidelines and algorithms. Schizophr Res 2012;134:219‐25.
    1. Mayoral‐van Son J, de la Foz VO, Martinez‐Garcia O et al. Clinical outcome after antipsychotic treatment discontinuation in functionally recovered first‐episode nonaffective psychosis individuals: a 3‐year naturalistic follow‐up study. J Clin Psychiatry 2016;77:492‐500.
    1. Winton‐Brown TT, Elanjithara T, Power P et al. Five‐fold increased risk of relapse following breaks in antipsychotic treatment of first episode psychosis. Schizophr Res 2017;179:50‐6.
    1. Karson C, Duffy RA, Eramo A et al. Long‐term outcomes of antipsychotic treatment in patients with first‐episode schizophrenia: a systematic review. Neuropsychiatr Dis Treat 2016;12:57‐67.
    1. McGorry P, Alvarez‐Jimenez M, Killackey E. Antipsychotic medication during the critical period following remission from first‐episode psychosis: less is more. JAMA Psychiatry 2013;70:898‐900.
    1. Alvarez‐Jimenez M, O'Donoghue B, Thompson A et al. Beyond clinical remission in first episode psychosis: thoughts on antipsychotic maintenance vs. guided discontinuation in the functional recovery era. CNS Drugs 2016;30:357‐68.
    1. Di Capite S, Upthegrove R, Mallikarjun P. The relapse rate and predictors of relapse in patients with first‐episode psychosis following discontinuation of antipsychotic medication. Early Interv Psychiatry (in press).
    1. Morrison AP, Turkington D, Pyle M et al. Cognitive therapy for people with schizophrenia spectrum disorders not taking antipsychotic drugs: a single‐blind randomised controlled trial. Lancet 2014;383:1395‐403.
    1. Howes OD, McCutcheon R, Agid O et al. Treatment‐resistant schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology. Am J Psychiatry 2017;174:216‐29.
    1. Harvey PD, Rosenthal JB. Treatment resistant schizophrenia: course of brain structure and function. Prog Neuropsychopharmacol Biol Psychiatry 2016;70:111‐6.
    1. Agid O, Arenovich T, Sajeev G et al. An algorithm‐based approach to first‐episode schizophrenia: response rates over 3 prospective antipsychotic trials with a retrospective data analysis. J Clin Psychiatry 2011;72:1439‐44.
    1. Kreyenbuhl JA, Medoff DR, McEvoy JP et al. The RAISE Connection Program: psychopharmacological treatment of people with a first episode of schizophrenia. Psychiatr Serv 2016;67:1300‐6.
    1. Williams R, Malla A, Roy M et al. What is the place of clozapine in the treatment of early psychosis in Canada? Can J Psychiatry 2017;62:109‐14.
    1. Zipursky RB, Agid O. Recovery, not progressive deterioration, should be the expectation in schizophrenia. World Psychiatry 2015;14:94‐6.
    1. Emsley R, Chiliza B, Asmal L. The evidence for illness progression after relapse in schizophrenia. Schizophr Res 2013;148:117‐21.
    1. Lieberman JA, Alvir JM, Koreen A et al. Psychobiologic correlates of treatment response in schizophrenia. Neuropsychopharmacology 1996;14(Suppl. 3):13S‐21S.
    1. Emsley R, Oosthuizen P, Koen L et al. Comparison of treatment response in second‐episode versus first‐episode schizophrenia. J Clin Psychopharmacol 2013;33:80‐3.
    1. McEvoy JP, Hogarty GE, Steingard S. Optimal dose of neuroleptic in acute schizophrenia. A controlled study of the neuroleptic threshold and higher haloperidol dose. Arch Gen Psychiatry 1991;48:739‐45.
    1. Andreasen NC, Liu D, Ziebell S et al. Relapse duration, treatment intensity, and brain tissue loss in schizophrenia: a prospective longitudinal MRI study. Am J Psychiatry 2013;170:609‐15.
    1. Emsley R, Nuamah I, Hough D et al. Treatment response after relapse in a placebo‐controlled maintenance trial in schizophrenia. Schizophr Res 2012;138:29‐34.
    1. Wiersma D, Nienhuis FJ, Slooff CJ et al. Natural course of schizophrenic disorders: a 15‐year followup of a Dutch incidence cohort. Schizophr Bull 1998;24:75‐85.
    1. Lally J, Ajnakina O, Di Forti M et al. Two distinct patterns of treatment resistance: clinical predictors of treatment resistance in first‐episode schizophrenia spectrum psychoses. Psychol Med 2016;46:3231‐40.
    1. Ucok A, Cikrikcili U, Karabulut S et al. Delayed initiation of clozapine may be related to poor response in treatment‐resistant schizophrenia. Int Clin Psychopharmacol 2015;30:290‐5.
    1. Howes OD, Vergunst F, Gee S et al. Adherence to treatment guidelines in clinical practice: study of antipsychotic treatment prior to clozapine initiation. Br J Psychiatry 2012;201:481‐5.
    1. Samara MT, Leucht C, Leeflang MM et al. Early improvement as a predictor of later response to antipsychotics in schizophrenia: a diagnostic test review. Am J Psychiatry 2015;172:617‐29.
    1. Wimberley T, Stovring H, Sorensen HJ et al. Predictors of treatment resistance in patients with schizophrenia: a population‐based cohort study. Lancet Psychiatry 2016;3:358‐66.
    1. Diaz‐Caneja CM, Pina‐Camacho L, Rodriguez‐Quiroga A et al. Predictors of outcome in early‐onset psychosis: a systematic review. NPJ Schizophr 2015;1:14005.
    1. McGorry P, Keshavan M, Goldstone S et al. Biomarkers and clinical staging in psychiatry. World Psychiatry 2014;13:211‐23.
    1. Fusar‐Poli P, Papanastasiou E, Stahl D et al. Treatments of negative symptoms in schizophrenia: meta‐analysis of 168 randomized placebo‐controlled trials. Schizophr Bull 2015;41:892‐9.
    1. Galderisi S, Mucci A, Bitter I et al. Persistent negative symptoms in first episode patients with schizophrenia: results from the European First Episode Schizophrenia Trial. Eur Neuropsychopharmacol 2013;23:196‐204.
    1. Melle I, Larsen TK, Haahr U et al. Prevention of negative symptom psychopathologies in first‐episode schizophrenia: two‐year effects of reducing the duration of untreated psychosis. Arch Gen Psychiatry 2008;65:634‐40.
    1. Mathalon DH. Challenges associated with application of clinical staging models to psychotic disorders. Biol Psychiatry 2011;70:600‐1.
    1. Fusar‐Poli P, Meyer‐Lindenberg A. Forty years of structural imaging in psychosis: promises and truth. Acta Psychiatr Scand 2016;134:207‐24.
    1. Duffy A, Malhi GS, Grof P. Do the trajectories of bipolar disorder and schizophrenia follow a universal staging model? Can J Psychiatry 2017;62:115‐22.
    1. McGorry PD. Pre‐emptive intervention in psychosis: agnostic rather than diagnostic. Aust N Z J Psychiatry 2011;45:515‐9.
    1. Leguay D. Advocacy for the establishment of a comprehensive strategy to reduce the “burden” of schizophrenic disorders. Encephale 2016;42:476‐83.

Source: PubMed

Подписаться