Interventionen bei Personen mit erhöhtem Psychoserisiko: Eine aktuelle Übersicht über randomisiert kontrollierte Studien

Zusammenfassung

Mit der Früherkennung und validen Erfassung des präpsychotischen Risikosyndroms und der sich daraus ableitenden indizierten Prävention verbindet sich die Hoffnung einer Verhinderung bzw. Verzögerung oder Abschwächung der drohenden psychotischen Ersterkrankung, einer Verbesserung der aktuellen Symptomatik und die Vermeidung bzw. Verzögerung der sich bereits in der Vorphase häufig abzeichnenden psychosozialen Behinderung. Mithilfe einer systematischen Literaturrecherche identifizierten wir sieben abgeschlossene, randomisierte und kontrollierte Studien zu Interventionen bei Personen mit erhöhtem Psychoserisiko. Diese Studien evaluierten antipsychotische, neuroprotektive, kognitiv-verhaltenstherapeutische und integrierte Behandlungsansätze. Insgesamt zeigten alle spezifischen Interventionen Vorteile gegenüber der jeweiligen Kontrollgruppe bezüglich der Interventionsziele – wenn auch zum Teil nur auf deskriptiver Ebene. Dieser Vorteil spezifischer Behandlung konnte durch eine erste Metaanalyse statistisch signifikant abgesichert werden. Aufgrund der Studienlage kann derzeit jedoch keine spezifische Empfehlung für eine der evaluierten Strategien gegeben werden. Daher sind Interventionen einer gründlichen Nutzen-/Risikoanalyse zu unterziehen, wobei die Höhe des individuellen Risikos im Verhältnis zu den geeigneten Interventionen und deren Nebenwirkungsprofil zu betrachten sind. Methodisch gut geplante Replikationen der vorgestellten Interventionen mit höheren Fallzahlen sowie eine differenzielle Evaluation der Behandlungsoptionen sind notwendig.

Abstract

Early and valid detection of the psychosis risk syndrome, and indicated prevention aim at preventing, delaying or ameliorating frank psychosis, improving current symptoms as well as emerging psychosocial disability. In a systematic literature search we identified seven completed randomised controlled trials of interventions for individuals at high risk of developing first episode psychosis. These studies evaluated antipsychotics, neuroprotective agents, cognitive behavioural and integrated treatment approaches. All trials reported advantages for specific interventions as compared to the respective control conditions (although not significant in each of the studies), which proved to be significant in the first meta-analysis of the studies. However, the current results do not allow recommendations for any specific treatment. Therefore, interventions should be thoroughly reviewed based on their risk/benefit ratio. The level of individual clinical risk, assumed benefits and side effects of interventions are critical determinants for these considerations. Future research is needed with sufficiently powered, methodologically sound replication studies, which are designed to explore differential efficacy of the interventions.

Schlüsselwörter

Psychose-Risikosyndrom - Personen mit erhöhtem Psychoserisiko - Prodrom - Behandlung - randomisierte kontrollierte Interventionsstudien - Übersicht

Key words

psychosis risk syndrome - person at risk for psychosis - prodrome - intervention - randomised controlled trials - review

• Literatur

• 1 McGorry PD, Yung AR, Phillips LJ. The “close-in” or ultra high-risk model: a safe and effective strategy for research and clinical intervention in prepsychotic mental disorder. Schizophr Bull 2003; 29: 771-790
• 2 Ruhrmann S, Schultze-Lutter F, Klosterkotter J. Probably at-risk, but certainly ill – advocating the introduction of a psychosis spectrum disorder in DSM-V. Schizophr Res 2010; 120: 23-37 DOI: 10.1016/j.schres.2010.03.015.
• 3 Yung AR, Phillips LJ, McGorry PD et al. Prediction of psychosis. A step towards indicated prevention of schizophrenia. Br J Psychiatry Suppl 1998; 172: 14-20
• 4 Yung AR, Phillips LJ, Yuen HP et al. Risk factors for psychosis in an ultra high-risk group: psychopathology and clinical features. Schizophr Res 2004; 67: 131-142 DOI: 10.1016/S0920-9964(03)00192-0.
• 5 Huber G. Psychiatrische Aspekte des Basisstörungskonzepts. In: Süllwold L, Huber G, (Hrsg) Schizophrene Basisstörungen. Berlin: Springer; 1986: 39-143
• 6 Huber G, Gross G, Schüttler R. Schizophrenie. Verlaufs- und Sozialpsychiatrische Langzeituntersuchung an den 1945–1959 in Bonn hospitalisierten schizophrenen Kranken. Berlin: Springer; 1979
• 7 Fusar-Poli P, Bonoldi I, Yung AR et al. Predicting psychosis: meta-analysis of transition outcomes in individuals at high clinical risk. Archives of general psychiatry 2012; 69: 220-229 DOI: 10.1001/archgenpsychiatry.2011.1472.
• 8 Addington J, Epstein I, Liu L et al. A randomized controlled trial of cognitive behavioral therapy for individuals at clinical high risk of psychosis. Schizophr Res 2011; 125: 54-61 DOI: 10.1016/j.schres.2010.10.015.
• 9 Amminger GP, Schafer MR, Papageorgiou K et al. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Archives of general psychiatry 2010; 67: 146-154 DOI: 10.1001/archgenpsychiatry.2009.192.
• 10 Bechdolf A, Wagner M, Ruhrmann S et al. Preventing progression to first-episode psychosis in early initial prodromal states. Br J Psychiatry 2012; 200: 22-29 DOI: 10.1192/bjp.bp.109.066357.
• 11 McGlashan TH, Zipursky RB, Perkins D et al. Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis. Am J Psychiatry 2006; 163: 790-799 DOI: 10.1176/appi.ajp.163.5.790.
• 12 McGorry PD, Yung AR, Phillips LJ et al. Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms. Archives of general psychiatry 2002; 59: 921-928
• 13 Morrison AP, French P, Walford L et al. Cognitive therapy for the prevention of psychosis in people at ultra-high risk: randomised controlled trial. Br J Psychiatry 2004; 185: 291-297 DOI: 10.1192/bjp.185.4.291.
• 14 Nordentoft M, Thorup A, Petersen L et al. Transition rates from schizotypal disorder to psychotic disorder for first-contact patients included in the OPUS trial. A randomized clinical trial of integrated treatment and standard treatment. Schizophr Res 2006; 83: 29-40 DOI: 10.1016/j.schres.2006.01.002.
• 15 Overall JE, Gorham DR. The Brief Psychiatric Rating Scale. Psychol Rep 1962; 10: 799-812
• 16 Beck AT. Cognitive Therapy and the Emotional Disorders. New York: Guilford Press; 1976
• 17 Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13: 261-276
• 18 Goldberg DP, Hillier VF. A scaled version of the General Health Questionnaire. Psychol Med 1979; 9: 139-145
• 19 Woods SW, Carlson JP, McGlashan TH. DSM-5 and the “Psychosis Risk Syndrome”: The DSM-5 proposal is better than DSM-IV. Psychosis 2010; 2: 187-190 DOI: 10.1080/17522439.2010.511719.
• 20 McGlashan TH, Miller TJ, Woods SW. A scale for the assessment of prodromal symptoms and states. In: Miller TJ, Mednick SA, McGlashan TH, et al. (Hrsg) Early Intervention in Psychotic Disorders. Dordrecht: Kluwer Academic Publishers; 2001: 135-139
• 21 Miller TJ, McGlashan TH, Woods SW et al. Symptom assessment in schizophrenic prodromal states. Psychiatr Q 1999; 70: 273-287
• 22 Miller TJ, McGlashan TH, Rosen JL et al. Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability. Schizophr Bull 2003; 29: 703-715
• 23 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 DOI: 10.1136/bmj.38565.415000.E01.
• 24 Miller TJ, McGlashan TH, Rosen JL et al. Prospective diagnosis of the initial prodrome for schizophrenia based on the Structured Interview for Prodromal Syndromes: preliminary evidence of interrater reliability and predictive validity. Am J Psychiatry 2002; 159: 863-865
• 25 Miller TJ, Zipursky RB, Perkins D et al. The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. II. Baseline characteristics of the “prodromal” sample. Schizophr Res 2003; 61: 19-30
• 26 French P, Morrisson AP. Early Detection and Cognitive Therapy for People at High Risk of Developing Psychosis. London: Wiley; 2004
• 27 Maurer KHF, Schmidt M, Trendler H et al. The early recognition inventory: structure, reliability and initial results. Schizophr Res 2004; 67
• 28 Bechdolf A, Wagner M, Veith V et al. Randomized controlled multicentre trial of cognitive behaviour therapy in the early initial prodromal state: effects on social adjustment post treatment. Early Interv Psychiatry 2007; 1: 71-78 DOI: 10.1111/j.1751-7893.2007.00013.x.
• 29 Bechdolf A, Knost B, Nelson B et al. Randomized comparison of group cognitive behaviour therapy and group psychoeducation in acute patients with schizophrenia: effects on subjective quality of life. Aust N Z J Psychiatry 2010; 44: 144-150 DOI: 10.3109/00048670903393571.
• 30 Bechdolf A, Schultze-Lutter F, Klosterkötter J. Self-experienced vulnerability, prodromal symptoms and coping strategies preceding schizophrenic and depressive relapses. Eur Psychiatry 2002; 17: 384-393
• 31 Morrison AP, French P, Parker S et al. Three-year follow-up of a randomized controlled trial of cognitive therapy for the prevention of psychosis in people at ultrahigh risk. Schizophr Bull 2007; 33: 682-687 DOI: 10.1093/schbul/sbl042.
• 32 Barlow DH. Negative effects from psychological treatments: a perspective. Am Psychol 2010; 65: 13-20 DOI: 10.1037/a0015643.
• 33 Yung AR, Phillips LJ, Nelson B et al. Randomized controlled trial of interventions for young people at ultra high risk for psychosis: 6-month analysis. J Clin Psychiatry 2011; 72: 430-440 DOI: 10.4088/JCP.08m04979ora.
• 34 Correll CU, Hauser M, Auther AM et al. Research in people with psychosis risk syndrome: a review of the current evidence and future directions. J Child Psychol Psychiatry 2010; 51: 390-431 DOI: 10.1111/j.1469-7610.2010.02235.x.
• 35 Phillips LJ, Nelson B, Yuen HP et al. Randomized controlled trial of interventions for young people at ultra-high risk of psychosis: study design and baseline characteristics. Aust N Z J Psychiatry 2009; 43: 818-829 DOI: 10.1080/00048670903107625.
• 36 Yung AR, Yuen HP, Berger G et al. Declining transition rate in ultra high risk (prodromal) services: dilution or reduction of risk?. Schizophr Bull 2007; 33: 673-681 DOI: 10.1093/schbul/sbm015.
• 37 Bechdolf A, Muller H, Stutzer H et al. Rationale and baseline characteristics of PREVENT: a second-generation intervention trial in subjects at-risk (prodromal) of developing first-episode psychosis evaluating cognitive behavior therapy, aripiprazole, and placebo for the prevention of psychosis. Schizophr Bull 2011; 37 (Suppl. 02) S111-121 DOI: 10.1093/schbul/sbr083.
• 38 Ruhrmann S, Schultze-Lutter F, Salokangas RK et al. Prediction of psychosis in adolescents and young adults at high risk: results from the prospective European prediction of psychosis study. Arch Gen Psychiatry 2010; 67: 241-251 DOI: 10.1001/archgenpsychiatry.2009.206.
• 39 Schultze-Lutter F, Schimmelmann BG, Ruhrmann S. The near Babylonian speech confusion in early detection of psychosis. Schizophr Bull 2011; 37: 653-655 DOI: 10.1093/schbul/sbr039.
• 40 Yang LH, Wonpat-Borja AJ, Opler MG et al. Potential stigma associated with inclusion of the psychosis risk syndrome in the DSM-V: an empirical question. Schizophr Res 2010; 120: 42-48 DOI: 10.1016/j.schres.2010.03.012.
• 41 Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials. J Pharmacol Pharmacother 2010; 1: 100-107 DOI: 10.4103/0976-500X.72352.
• 42 Tarrier N, Wykes T. Is there evidence that cognitive behaviour therapy is an effective treatment for schizophrenia? A cautious or cautionary tale?. Behav Res Ther 2004; 42: 1377-1401 DOI: 10.1016/j.brat.2004.06.020.
• 43 Preti A, Cella M. Randomized-controlled trials in people at ultra high risk of psychosis: a review of treatment effectiveness. Schizophr Res 2010; 123: 30-36 DOI: 10.1016/j.schres.2010.07.026.
• 44 Kelly C, Hadjinicolaou AV, Holt C et al. Meta-analysis of medical and non-medical treatments of the prodromal phase of psychotic illness in at-risk mental states. Psychiatr Danub 2010; 22 (Suppl. 01) S56-S62
• 45 Marshall M, Rathbone J. Early intervention for psychosis. Cochrane Database Syst Rev 2011; 6: CD004718, DOI: 10.1002/14651858.CD004718.pub3
• 46 Ruhrmann S, Schultze-Lutter F, Klosterkötter J. Intervention in the at-risk state to prevent transition to psychosis. Curr Opin Psychiatry 2009; 22: 177-183 DOI: 10.1097/YCO.0b013e328324b687.
• 47 DeLisi LE (Hrsg) Schizophrenia. Research; 2001
• 48 Bechdolf A, Peukert R. Psychosis prevention: expectations met. Psychiatr Prax 2011; 38: 58-60 DOI: 10.1055/s-0030-1266056.
• 49 Bechdolf AJG. Psychoedukation bei Personen mit erhöhtem Psychoserisiko. Stuttgart: Schattauer; 2006
• 50 Haroun N, Dunn L, Haroun A et al. Risk and protection in prodromal schizophrenia: ethical implications for clinical practice and future research. Schizophr Bull 2006; 32: 166-178 DOI: 10.1093/schbul/sbj007.
• 51 Hauser M, Lautenschlager M, Gudlowski Y et al. Psychoeducation with patients at-risk for schizophrenia – an exploratory pilot study. Patient Educ Couns 2009; 76: 138-142 DOI: 10.1016/j.pec.2008.11.003.
• 52 Bechdolf A, Phillips LJ, Francey SM et al. Recent approaches to psychological interventions for people at risk of psychosis. Eur Arch Psychiatry Clin Neurosci 2006; 256: 159-173 DOI: 10.1007/s00406-006-0623-0.
• 53 Häfner HBA, Klosterkötter J, Maurer K. Psychosen – Früherkennung und Frühintervention. Stuttgart: Schattauer; 2011
• 54 Morrison AP, Stewart SL, French P et al. Early detection and intervention evaluation for people at high-risk of psychosis-2 (EDIE-2): trial rationale, design and baseline characteristics. Early Interv Psychiatry 2011; 5: 24-32 DOI: 10.1111/j.1751-7893.2010.00254.x.
• 55 Nelson B, McGorry P, Yung A et al. The NEURAPRO (North America, Europe, Australia prodrome) study: a multicenter RCT of treatment strategies for symptomatic patients at ultra-high risk for progression to schizophrenia and related disorders. Design and study plan. Schizophr Res 2008: 102 (Suppl 2): 155