The need–adapted integrated treatment in Sant Pere Claver–Early Psychosis Program (SPC–EPP) in Barcelona, Spain

El tratamiento integrado y adaptado a las necesidades del Programa de Psicosis Incipiente-Sant Pere Claver (PPI-SPC) en Barcelona, España

Tecelli Domínguez Martínez,^1,2 Elias Vainer,³ Ma. Antonia Massanet,³ Iván Torices,³ Mercè Jané,³ Neus Barrantes–Vidal^1,3,4,5

¹ Universitat Autónoma de Barcelona, Departamento de Psicología Clínica y de la Salud, Barcelona.

² Ministerio de Asuntos Exteriores y de Cooperación y la Agencia Española de Cooperación Internacional para el Desarrollo (MAEC–AECID).

⁴ CIBERSAM– Instituto de Salud Carlos III, Barcelona.

⁵ University of North Carolina at Greensboro, USA.

Correspondencia:
Neus Barrantes Vidal. Departament de Psicologia Clínica i de la Salut.
Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona).
Tel.: +3493 581 3864. Fax: +3493 581 2125.
E–mail: Neus.Barrantes@uab.cat

SUMMARY

International interest has grown over the past 15 years in the prognostic potential of early identification and intervention in the prodromal and first–episode phases of psychosis. This focus is associated with increasing optimism about the benefits of implementing treatment as early as possible in the course of psychosis, at least to help improve the course of illness, reducing its long–term impact.

A clearer framework for guiding, designing, and evaluating preventive interventions in mental disorders has been developed. As a consequence, a series of research projects and real–world services systems are currently emerging. Additionally, several influential international figures and research groups have developed and cooperated in disseminating a more optimistic set of ideas concerning early intervention in psychosis.

The early psychosis programs developed worldwide have a number of common elements and goals: a) early detection of new cases, b) reducing the duration of untreated psychosis (DUP), and c) providing better and continued treatment during the <<critical period>> of the early years of the disorder.

Moreover, family interventions usually offer psychoeducation and/or individual and group family therapy, in conjunction with communication and problem solving training, which can help to develop coping strategies and reduce distress and burden.

Intervention programs in early psychosis are usually composed by interdisciplinary teams, providing a wide range of integrated services that typically include psychoeducation, clinical case management, and group interventions. Specific interventions generally include pharmacotherapy, stress management, relapse prevention, social and employment rehabilitation support, and cognitive and family therapy.

The current challenges in the implementation of psychological interventions in the early stages of psychosis are: 1. to adapt treatment modalities that have been proven effective in stable and residual stages of the disease to its early stages; 2. to develop new forms of therapy tailored to the specific characteristics of these early stages of psychosis; and 3. treatment packages need to be individually tailored to specific needs rather than applied homogenously across early psychosis patients.

Following the experience and work of Alanen et al., an Early Psychosis Program (EPP) currently is being developed in the Mental Health Services of Sant Pere Claver in Barcelona, addressed to young people between 14 and 35 years with at risk mental states (ARMS), first episode psychosis (FEP), and post–crisis stages of psychosis.

All cases included in the program are derived from various community resources (primary health care, schools, emergency services, and inpatient units for acute patients) and assessed exhaustively by the team to define the treatment plan for each case. The treatment modalities offered by the EPP are: individual and group therapy, unifamiliar and multifamiliar psychotherapy, psychoeducation and pharmacotherapy in those cases where necessary. Furthermore, there is an intensive community support for those patients who have difficulties engaging with mental health services. During the EPP all patients are monitored through weekly visits with their psychiatrist, psychologist, social worker and/or nursing staff.

The aim of this paper is to present and describe the integrated need–adapted treatment approach of the early psychosis program currently being developed in a specialized center in Barcelona (Spain).

Key words: Early detection and intervention, early psychosis, psychotherapeutic approach, need–adapted treatment.

RESUMEN

Los trastornos del espectro psicótico presentan un curso crónico y episódico que provoca alteraciones en todas las áreas de la vida, generando importantes grados de discapacidad, pérdida de funciones psicosociales, grandes costes económicos, una comorbilidad considerable y sufrimiento tanto para los pacientes como para sus familias. A pesar de que el tratamiento farmacológico y psicosocial ha ayudado a aliviar los síntomas y mejorar la calidad de vida, en muy pocas ocasiones se logra una recuperación satisfactoria en los niveles psicológico y funcional.

Durante los últimos 15 años, el optimismo creciente sobre la posibilidad de mejorar el pronóstico de la psicosis y alterar con ello el tradicional curso negativo de la enfermedad, ha producido una reforma sustancial en la práctica clínica y en el desarrollo de estrategias de intervención temprana en muchos países. De esta manera, el desplazamiento del foco de atención desde las fases estables o residuales de la psicosis hacia los inicios de la misma está suponiendo una serie de innovaciones y avances, tanto en la evaluación y diagnóstico, como en las modalidades terapéuticas y en la consiguiente reordenación de los servicios asistenciales.

Cada vez existen más grupos en todo el mundo que establecen programas clínicos e iniciativas de investigación centradas en la psicosis temprana. Cada uno de estos programas tiene características particulares y rasgos propios en cuanto a las modalidades de tratamiento o los instrumentos de evaluación, pero la mayoría comparte una serie de elementos y objetivos en común: a) detectar de forma precoz nuevos casos; b) reducir el periodo de tiempo desde que el paciente presenta una sintomatología claramente psicótica hasta que recibe un tratamiento adecuado (duración de la psicosis no tratada); y c) proporcionar un mejor y continuo tratamiento en el <<periodo crítico>> de los primeros años de la enfermedad.

Los programas de intervención en la psicosis temprana están formados habitualmente por equipos interdisciplinarios que proporcionan una amplia serie de servicios integrados que suelen incluir psicoeducación, manejo clínico de casos e intervenciones grupales. Las intervenciones específicas incluyen generalmente farmacoterapia, manejo de estrés, prevención de recaídas, apoyo y rehabilitación social y laboral, así como terapia familiar y cognitiva.

El desafío actual en la aplicación de intervenciones en la psicosis temprana consiste en: 1. conseguir adaptar aquellas modalidades de tratamiento que ya han demostrado su eficacia en las fases estables y residuales de la enfermedad a los inicios de la misma; 2. integrar y desarrollar nuevas formas de terapia que se adapten a las características específicas de cada una de las fases iniciales de la psicosis (fase prodrómica o de alto riesgo, inicio de la psicosis o primer episodio de psicosis y <<fase crítica>> o poscrisis); y 3. adecuar los tratamientos de manera individual en vez de aplicarlos de forma homogénea.

Un ejemplo de la integración de todos estos aspectos es el <<tratamiento integrado y adaptado a las necesidades>> desarrollado por el grupo de Alanen et al. en Finlandia, que combina diferentes formas de tratamiento de una manera flexible y diseñadas en función de las necesidades de cada caso. Tomando como base el trabajo del grupo finlandés, actualmente se está llevando a cabo un Programa de Psicosis Incipiente (PPI) en la Fundació Sanitária Sant Pere Claver de Barcelona, destinado a jóvenes entre 14 y 35 años con estados mentales de alto riesgo (EMAR), primeros episodios de psicosis (PEP) y en la fase poscrisis psicótica. Los casos incluidos en el programa derivan de diversos recursos comunitarios (atención primaria, psicólogos de las escuelas, servicio de urgencias hospitalarias, unidad de agudos, etc.) y valorados exhaustivamente por el equipo asistencial para definir el tipo de tratamiento en función de las necesidades particulares del paciente y de su entorno. Las modalidades de tratamiento que ofrece el PPI son: terapia individual y grupal, psicoterapia unifamiliar, psicoterapia multifamiliar, psicoeducación y tratamiento farmacológico en aquellos casos que sea necesario. Además, se cuenta con un profesional que hace visitas a domicilio, da seguimiento y tratamiento asertivo comunitario a aquellos pacientes que tienen dificultades para acceder y mantener una vinculación con los servicios de salud mental. Durante el PPI todos los pacientes tienen visitas de seguimiento semanal con el psiquiatra referente, el psicólogo(a), trabajador(a) social y/o el personal de enfermería.

El objetivo del presente artículo es presentar y describir el tratamiento integrado y adaptado a las necesidades del Programa de Psicosis Incipiente–Sant Pere Claver (PPI–SPC) que se está llevando a cabo actualmente en un centro especializado de Barcelona (España).

Palabras clave: Detección e intervención temprana, psicosis incipiente, tratamiento integrado y adaptado a las necesidades.

INTRODUCTION

After decades of research, and despite advances in pharmacological and psychotherapeutic interventions, schizophrenia–spectrum disorders are still among the most debilitating disorders in medicine.¹ Most patients suffer chronic impairment in all life domains, which has huge personal, social and economic costs.²

In recent years there has been increasing confidence that preventive intervention in psychotic disorders might be a realistic proposition in clinical settings.^3,4 Early detection and intervention programs have been initiated worldwide, beginning with Yung et al.⁵ in Australia and then moving to the United States and Europe shortly thereafter.

The focus on specific treatments aimed at preventing progression to psychosis or promoting recovery in those who have experienced a psychotic episode has tended to be classified into three main categories: 1. prodromal or <<at risk mental state (ARMS)>> phase; 2. onset or first episode psychosis (FEP); 3. post–psychosis phase, also known as <<critical period>>, covering the period following recovery from FEP to up to five years subsequently.⁹

Most groups working with the ultra high risk (UHR) population have attempted to engage patients in various psychological interventions using a recovery model of treatment. These interventions usually include case management, individual therapy, psychoeducation, cognitive–behavioral therapy (CBT), multifamily groups, and also give support for education and employment.¹⁰ Family interventions usually focus on individual and group work, psychoeducation and the development of coping strategies to help reduce distress and burden.¹¹ However, specific interventions such as problem–solving and communication skills training have also been suggested as possible interventions that may improve the functional prognosis of young people at UHR for psychosis.¹²

Given the complex etiology and clinical manifestation of psychosis, treatment packages for people experiencing early psychosis need to be individually tailored to specific needs rather than applied homogenously across early psychosis patients.¹³ One example is the work of the group leaded by Alanen et al.^14,15 in Finland, which has created a need–adapted treatment approach, considering in each case both individual and interactional factors. They combine different forms of treatment in a flexible, individually designed intervention, in order to take into account the needs of both patients and families, using psychoeducational principles in combination with medication, family intervention techniques, and individual psychotherapy.

Based directly on the work of Alanen et al., there is an early intervention program currently being developed in a specialized center in Barcelona, which is presented below.

The Sant Pere Claver – Early Psychosis Program (SPC–EPP)

The Mental Health and Addictions Plan of the Department of Mental Health from the Catalonian Government promotes specific programs in order to serve young people with early psychotic disorders (PAE–TPI–Programas de Atención Específica a los jóvenes con Trastornos Psicóticos Incipientes). The Early psychosis programs have been implemented in a few settings in Catalonia. One of these programs is set at the Mental Health Centers of the Sant Pere Claver sanitary foundation (SPC), with a catchment area comprising two large districts of Barcelona, where 44500 inhabitants are within the at–risk age group (14–35 years).

The SPC is composed of two Communitary Mental Health Centers for Adults (CSMA–Sants and CSMA–Montjuïc), one for adolescents and children (CSMIJ), and one Day Hospital (HD) for adolescents.

General aims of SPC–EPP. At the start of the SPC–EPP, Alanen et al. provided training to the clinicians directly involved in the program. Consistent with this formative experience and following the pioneering work of Yung et al.⁵ and based on the recommendations of a clinical guide for early psychosis of the Spanish and Catalonian governments,^16,17 the main aims of SPC–EPP are:

1. To identify within a short period of time people at high risk for developing psychosis and people with FEP.

2. To encourage ARMS and FEP individuals to seek and adhere to earlier effective help.

3. If possible, to provide psychological, pharmacological and psychosocial treatment prior to the onset of the frank psychotic symptoms, in order to prevent the onset of the full psychotic disorder and to minimize DUP, associated morbidity, stigma, and possible brain damage.

4. To intensify treatment of the FEP to a) optimize recovery; b) prevent relapse, social exclusion, and vocational disruption; c) reduce co–morbidity such as depression, substance abuse, and suicide.

5. To improve symptomatic and functional outcomes and reduce secondary morbidity to improve the quality of life of both families and patients.

6. To promote sensitization of General Practitioners (GPs) and coordination with different health services, as well as with scholar and social resources.

METHOD

Inclusion and exclusion criteria

Paths to care and populations

As shown in figure 1, patients are referred to the program from a variety of communitary resources: primary health care (GPs), school psychologists, emergency services, and inpatient units for acute patients.

In order to increase the detection of potential ARMS cases, the SPC–EPP psychologists and psychiatrists visit weekly primary health care units. Also, nurses make regular visits to inpatient units of acute patients to detect FEP and promote their adherence to the program.

As shown in figure 1, after the first request for assistance, there is a weekly team meeting where it is evaluated whether the new cases fulfill the criteria for entering the program and assessment is carried out to determine the appropriate treatment.

Assessment procedures

As it can be seen in figure 1, there are different types of assessments with the goal of exploring the case in depth and defining the type of work to be done in each particular case (as outlined in tables 2 and 3).

a) Psychiatric diagnosis: Initial clinical interview, detailed history, diagnosis and, if necessary, drug prescription (minimum dose) as established by the Clinical Guide of the Spanish Government.¹⁶ Subsequently, the case is reported to the clinicians specifically involved in SPC–EPP for the general team meeting discussion.

b) Family assessment: There are at least four family interviews in which all family members are invited to attend with the patient. These interviews are aimed at analyzing the family status and yield an indication of treatment for both the patient and the family. Before the last interview, the case is discussed in the team meeting to tailor the treatment plan. There is always a feedback meeting with the family and the patient to inform them about the treatment plan, usually done after the case has been monitored and discussed in the team weekly meeting.

]]> c) Social assessment: Since the first contact, the social worker follows the case, initially weekly and then fortnightly, in order to help the patient to not disengage from studies or work.

d) Nursing assessment: For FEP, the nurse makes an initial contact with the patient before s/he is discharged from acute units (if applicable), and is also involved in following him/her up in the hospital if there is a relapse. Since the first contact with the service, the nurse performs an initial assessment of the patient's health and establishes an action plan including goals to achieve (general health advice to improve quality of life as personal hygiene, nutrition, personal care, etc.) always in accordance with the patient.

Nurses are also in charge of making blood extraction for health and genetics analyses.

e) Research assessment: It is undertaken by the research team independently of the treatment team. All patients are assessed prospectively: at baseline (at the moment of inclusion in the program), and at 6 and 12 months with standardized measures to assess changes across time on clinical, functional, psychological and neurocognitive factors. These results are always communicated to the professional responsible for each case in order to contribute in the design of the intervention.

Treatment modalities

Following the work of Alanen et al.,^14,15 known as <<need–adapted treatment of psychodynamic orientation>>, the psychotherapeutic approach is based on the idea of <<flexibility in accordance with the needs>>. Because of the heterogeneous nature of schizophrenic psychoses, the treatment of these patients must always be planned individually and on case–specific premises, taking into account the therapeutic needs of both the patients and the people closest to them.^14,15,20,21

The psychodynamic approach used in SPC–EPP places emphasis on increasing self–knowledge and establishing a sense of psychotic experiences in the world within the person. In addition, the main focus of the treatment process is the relationship between people and their environment.

The main principles of the need–adapted approach

Following Alanen et al.,^14,15,20 the main principles of the need–adapted approach are:

1. The therapeutic activities are planned and carried out flexibly and individually in each case. This principle also implies that unnecessary treatment should be avoided.

2. Examination and treatment are dominated by a psychotherapeutic attitude, to understand what has happened and is happening to the patients and their relatives.

3. The different therapeutic activities should support and not impair each other. For that, the promotion of cooperation and division of tasks between members of the different staff categories and workers of the different units of a given catchment area is especially important.

4. Quality of the process of therapy is clearly perceived through the continuous assessment during the course and outcome of the treatment, which involves the possibility of modifying the therapeutic plans.

5. The Outreach Assertive Community Treatment is a key part of the SPC–EPP. It is focused on improving the therapeutic alliance and offering treatment in the community, giving intensive support and follow–up through home visits to all patients who have special difficulties in engaging with mental health service.

6. Supervisory activities should become an inseparable part of the therapeutic work.

As shown in figure 1, patients of SPC–EPP can be treated with individual or group psychotherapy and treatment is also always offered to relatives. The specific modality varies according to the conclusions reached after the assessment and team consensus. We describe in tables 2 and 3 the specific features and aims of each type of treatment possibility for both patients (ARMS and FEP) and families. Family psychotherapy, specially multifamily groups, is based on the principles and work of Fulkes and Anthony,²² Bion,²³, García Badaracco²⁴ and Räkköláinen.²¹ In addition to the therapeutic modalities defined, all patients are visited and followed–up individually by the referent psychiatrist, psychologist, social worker, and nurse at least during the entire program (5 years). Also, the Outreach Assertive Community Treatment gives an intensive support and follow–up through home visits to all patients who have special difficulties in engaging with mental health service, in order to improve their therapeutic alliance and offer them treatment in the community.

Pharmacotherapy

In ARMS patients, pharmacological treatment is prescribed only if necessary, for example, when there is a rapid deterioration, when there is a risk of suicide or a risk of aggression to others or to patients themselves.

Sant Pere Claver Research Project (SPC–RP)

There is a joint research project between SPC and the Autonomous University of Barcelona (UAB) on the SPC–EPP: The Interaction between Daily–Life Stressors and Subjective Appraisals of Psychotic–Like Symptoms in the Psychosis Prodrome during One Year Follow–up: Ecological and Dynamic Evaluation with the Experience Sampling Methodology and Analysis of Gene–Environment (Stress) Interactions (P.I: N.Barrantes–Vidal), funded by La Fundació La Marató TV3, a charity foundation focused on scientific research of diseases that currently have no definitive cure.

This project prospectively examines dynamic relations between daily–life stressors and psychotic–like symptoms in ARMS and FEP individuals, and will delineate disorder and resilience trajectories over one year using Experience Sampling Methodology (ESM). ESM is an intensive research method that can be used to study emotional reactivity to stress through a structured dialy technique, assessing cognition, affect, symptoms and contextual factors in daily life.²⁸ The participants are assessed on clinical, functional, neurocognitive, and genetic assessments at baseline, 6 months and 1–year follow–up. Preliminary results from this study have been recently presented.^29–31

FINAL REMARKS

Our program is designed to meet the special needs of young people in the early stages of psychosis, people recovering from early psychosis and their families. We offer early treatment including both individual and group therapies designed to meet specific needs. Through our family intervention component, families are actively included and involved in the program. Finally, we have an ongoing evaluation of patients' outcomes; these results will be detailed elsewhere.

The training in early psychosis that has been given to the clinicians facilitated the detection and led to greater inclusion of cases in the program. Thus, the number of cases treated in SPC–EPP has tripled since 2007.

In our experience, the integration of psychodynamic concepts can have a significant contribution to contemporary approaches, especially if different techniques are used as an integrated model that emphasizes the tailoring of treatments according to the patients and family needs.

AKNOWLEDGEMENTS

This work has been possible thanks to the support of La Fundació la Marató TV3 (ATTRM059). Neus Barrantes–Vidal is funded by the Spanish Ministry of Science and Innovation: (Plan Nacional de I+D+I (PSI2008–04178), and the Generalitat de Catalunya, Suport als Grups de Recerca (SGR200972). Tecelli Domínguez Martínez thanks the Spanish Foreign Ministry (MAEC–AECID) for the PhD grant. We want to specially thank Joan Manel Blanqué, Jordi Codina, Mónica Montoro, Lluis Mauri, Ramón Berni, Cristina González and David Clusa for their comments and collaboration in the preparation of this manuscript. We thank the support offered by Fundació Sanitária Sant Pere Claver and all their clinicians for making the SPC–EPP possible.

REFERENCES

1. Hegarty JD, Baldessarini RJ, Tohen M, Waternaux C et al. One hundred years of schizophrenia: a meta–analysis of the outcome literature. Am J Psychiatry 1994;151:1409–1416.         [ Links ]

2. Corell CU, Hauser M, Auther AM, Cornblatt BA. Research in people with psychosis risk syndrome: a review of the current evidence and future directions. J Child Psychol Psychiatry 2010;51:390–431.         [ Links ]

3. Birchwood M, McGorry P, Jackson H. Early intervention in schizophrenia. Br J Psychiatry 1997;170:2–5.         [ Links ]

4. McGorry PD. Preventive strategies in early psychosis: verging on reality. Br J Psychiatry 1998;172:1–2.         [ Links ]

5. Yung A, McGorry P, McFarlane CA, Jackson HJ et al. Monitoring and care of young people an incipient risk of psychosis. Schizophr Bull 1996;22:283–303.         [ Links ]

6. Birchwood M, Fowler D, Jackson C. Early intervention in psychosis. A guide to concepts, evidence and interventions. Chichester, New York, Weinheim, Brisbane, Singapore, Toronto: Wiley; 2002.         [ Links ]

7. Gleeson J, McGorry P (eds). Intervenciones psicológicas en la psicosis temprana. Un manual de tratamiento. Bilbao: Biblioteca de Psicología Declée de Brouwer; 2005.         [ Links ]

8. Martindale BV, Bateman A, Crowe M, Margison F (eds). Las psicosis. Los tratamientos psicológicos y su eficacia. Barcelona: Editorial Herder; 2009.         [ Links ]

9. McGorry PD. The recognition and optimal management of early psychosis: an evidence–based reform. World Psychiatr 2002;1:76–83.         [ Links ]

10. Bhangoo RK, Carter CS. Very early intervention in psychotic disorders. Psychiatr Clin N Am 2009;32:81–94.         [ Links ]

11. Addington J, Collins A, McCleery A, Addington D. The role of family work in early psychosis. Schizophr Res 2005;79:77–83.         [ Links ]

12. O'Brien M, Zinberg JL, Ho L, Rudd A et al. Family problem solving interactions and 6 month symptomatic and functional outcomes in youth at ultra–high risk for psychosis and with recent psychotic symptoms: A longitudinal study. Schizophr Res 2009;107:198–205.         [ Links ]

13. Haddock G, Lewis S. Psychological intervention in early psychosis. Br J Psychiatry 2005;31:667–704.         [ Links ]

14. Alanen YO, Räkköláinen V, Aaltonen J. Need–adapted treatment of new schizophrenic patients: experiences and results of the Turku Project. Acta Psychiatr Scand 1991;83:363–372.         [ Links ]

15. Alanen Y. Schizophrenia. Its origins and need–adapted treatment. London: Karnac books; 1997.         [ Links ]

16. Guía de práctica clínica sobre la esquizofrenia y el trastorno psicótico incipiente. Madrid: Plan de calidad para el Sistema Nacional de Salud del Ministerio de Sanidad y Consumo. Agència d'Avaluació de Tecnologia i Recerca Mèdiques;2009. http://www.gencat.cat/salut/depsan/units/aatrm/html/ca/dir303/doc13319.html        [ Links ]

17. Fòrum Salut Mental, Proposta de desenvolupament d'un model d'atenció als trastorns psicòtics incipients, <<Document de treball>>, Barcelona: Fòrum de Salut Mental; 2006.         [ Links ]

18. Yung A, Pan Yuen H, McGorry PD, Phillips LJ et al. Mapping the onset of psychosis: the Comprehensive Assessment of At–Risk Mental States. Aust N Z J Psychiatry 2005;39:964–971.         [ Links ]

19. Schultze–Lutter F, Addington J, Ruhrmann S, Klosterkötter J. Schizophrenia pronness instrument. Adult Version (SPI–A) Roma: Giovanni Fioriti Editore; 2007.         [ Links ]

20. Alanen YO, Lehtinen V, Lehtinen K, Aaltonen J et al. El modelo finlandés integrado para el tratamiento precoz de la esquizofrenia y psicosis afines. En: Martindale BV, Bateman A, Crowe M, Margison F (eds). Las psicosis. Los tratamientos psicológicos y su eficacia. Barcelona: Editorial Herder; 2009.         [ Links ]

21. Räkköláinen V, Lehtinen K, Alanen YO. Need–adapted treatment of schizophrenic processes: the essential role of family–centered therapy meetings. Contemp Fam Treat 1991;13:573–582.         [ Links ]

22. Foulkes SH, Anthony EJ. Psicoterapia psicoanalítica de grupo. Buenos Aires: Paidos; 1964.         [ Links ]

23. Bion W. Experiences in groups. New York: Basic Books; 1976.         [ Links ]

24. García Badaracco J. Psicoanálisis multifamiliar. Los otros en nosotros y el descubrimiento de sí mismo. Buenos Aires: Paidós; 2000.         [ Links ]

25. Lieberman JA. Atypical antipsychotic drugs as a first–line treatment of schizophrenia: a rationale and hypotheses. J Clin Psychiatry 1996;57:68–71.         [ Links ]

26. McGlashan TH, Zipursky RB, Perkins MD, Addington J et al. Randomized double–blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis. Am J Psychiatry 2006;163:790–799.         [ Links ]

27. Woods SW, Breier A, Zipursky RB. Randomized trial of olanzapine versus placebo in the symptomatic acute treatment of the schizophrenic prodrome. Biol Psychiatry 2003;54:453–464.         [ Links ]

28. Myin–Germeys I, Van Os J. Stress–reactivity in psychosis: Evidence for an affective pathway to psychosis. Clin Psychol Rev 2007;27:409–424.         [ Links ]

29. Domínguez T, Vilagrà R, Blanqué JM, Vainer E et al. The association between relatives' Expressed Emotion with clinical and functional features of early–psychosis patients. Presented at: 7th International Conference on Early Psychosis (Amsterdam, NL), November 2010. Early Interv Psychiatry 2010;a:4:55.         [ Links ]

30. Domínguez T, Vilagrà R, Blanqué JM, Vainer E et al. Levels of Emotional Over–involvement (EOI) and Critical Comments (CC) in relatives of first episode psychosis and at risk mental state patients. Presented at: 7th International Conference on Early Psychosis (Amsterdam, NL), November 2010. Early Interv Psychiatry 2010;b:4:128.         [ Links ]

31. Vilagrà R, Domínguez T, Blanqué JM, Vainer E et al. Impact of depression on psychotic symptoms in at risk mental state and first episode psychosis patients. Presented at: 7th International Conference on Early Psychosis (Amsterdam, NL), November 2010. Early Interv Psychiatry 2010;4:83.         [ Links ]

32. Jorgensen P, Nordentoft M, Abel MB, Gouliaev G et al. Early detection and assertive community treatment of young psychotics: The OPUS Study. Rationale and design of the trial. Soc Psychiatr Psychiatric Epidemiol 2000;35:283–287.         [ Links ]