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Polypharmazie bei schizophrenen Psychosen

Polypharmacy in schizophrenia

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Zusammenfassung

Hintergrund

Während die meisten Leitlinien zur Schizophrenietherapie die Monotherapie mit Antipsychotika der 2. Generation empfehlen, werden im klinischen Alltag, insbesondere in Fällen therapieresistenter Symptome, sehr häufig multiple psychotrope Substanzen eingesetzt.

Methoden

Anhand einer aktuellen Literaturrecherche in öffentlich zugänglichen Datenbanken (Medline/OVID, google, http://www.clinicaltrials.gov) im Oktober 2009 und eigener Forschung wird die empirische Basis für Polypharmazie dargelegt und ihre Relevanz für die klinische Praxis erörtert.

Ergebnisse

Polypharmazie ist die Antwort auf verschiedene Aspekte der Therapieresistenz. Die Augmentation von Antipsychotika mit Antidepressiva erscheint zur Therapie der Negativsymptomatik oder komorbider depressiver Episoden empfehlenswert. Dagegen fehlt für die zusätzliche Gabe von Lithium oder Antiepileptika als Stimmungsstabilisatoren überzeugende Evidenz, wobei spezifische Subgruppen durchaus profitieren können. Da sich bislang keine pharmakologische Add-on-Strategie als überzeugend wirksam erwiesen hat, sollten zur Verbesserung der kognitiven Leistungsfähigkeit Antipsychotika mit psychotherapeutischen Trainingsmethoden kombiniert werden. Akute dystone Bewegungsstörungen sprechen auf Anticholinergika an, während sich Benzodiazepine bei akuten Anspannungs- und Angstsyndromen als wirksam erweisen. Therapieresistente Positiv- und Negativsymptome respondieren oftmals auf Clozapin in Monotherapie. In Einzelfällen kann eine kombinierte antipsychotische Therapie sinnvoll sein.

Schlussfolgerungen

Insgesamt muss die empirische Basis für Add-on-Strategien anhand weiterer randomisierter Vergleiche gegenüber aktiver und Placebokontrolle (RCT), aber auch naturalistischer Studien erweitert werden.

Summary

Background

While most guidelines recommend monotherapy with second-generation antipsychotics (SGA) in schizophrenia, the combined application of multiple psychotropic agents is very common, especially in treatment-refractory cases.

Methods

This review summarizes the evidence of combined antipsychotic treatment strategies and the augmentation of antipsychotics with mood stabilizers, antidepressants and experimental substances, based on publications accessible in public databases (Medline/Ovid, Google, http://www.clinicaltrials.gov) up to October 2009.

Results

Polypharmacy aims to address several aspects of treatment resistance and side effects of antipsychotics. Some evidence supports the augmentation of antipsychotics with antidepressants for negative symptoms and comorbid major depressive episodes. The add-on of lithium and mood stabilizers lacks compelling evidence but might be beneficial for specific subgroups. For treatment-resistant cognitive symptoms, cognitive re-mediation seems most promising as no pharmacological add-on strategy has gained convincing evidence so far. Acute dystonic movements should be treated with anticholinergic agents while agitation and anxiety might respond to short-term application of benzodiazepines. Treatment-resistant positive and/or negative symptoms should primarily lead to clozapine monotherapy; the add-on of a second SGA may be considered in single cases.

Conclusions

In general, rigorous data on combination therapy in schizophrenia are rare, and further randomized controlled trials (RCT), naturalistic and head-to-head-studies are necessary.

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Literatur

  1. Afshar H, Roohafza H, Mousavi G et al (2009) Topiramate add-on treatment in schizophrenia: a randomised, double-blind, placebo-controlled clinical trial. J Psychopharmacol 23:157–162

    Article  PubMed  CAS  Google Scholar 

  2. Akhondzadeh S, Malek-Hosseini M, Ghoreishi A et al (2008) Effect of ritanserin, a 5HT2A/2C antagonist, on negative symptoms of schizophrenia: a double-blind randomized placebo-controlled study. Progr Neuropsychopharmacol Biol Psychiatry 32:1879–1883

    Article  CAS  Google Scholar 

  3. Akhondzadeh S, Mohammadi N, Noroozian M et al (2009) Added ondansetron for stable schizophrenia: a double blind, placebo controlled trial. Schizophr Res 107:206–212

    Article  PubMed  Google Scholar 

  4. Amiel JM, Mangurian CV, Ganguli R et al (2008) Addressing cardiometabolic risk during treatment with antipsychotic medications. Curr Opin Psychiatry 21:613–618

    Article  PubMed  Google Scholar 

  5. Andreasen NC, Carpenter WT Jr, Kane JM et al (2005) Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry 162:441–449

    Article  PubMed  Google Scholar 

  6. Barbui C, Signoretti A, Mule S et al (2009) Does the addition of a second antipsychotic drug improve clozapine treatment? Schizophr Bull 35:458–468

    Article  PubMed  Google Scholar 

  7. Chang JS, Ahn YM, Park HJ et al (2008) Aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 69:720–731

    Article  PubMed  CAS  Google Scholar 

  8. Citrome L (2009) Adjunctive lithium and anticonvulsants for the treatment of schizophrenia: what is the evidence? Expert Rev Neurother 9:55–71

    Article  PubMed  CAS  Google Scholar 

  9. Correll CU, Rummel-Kluge C, Corves C et al (2009) Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials. Schizophr Bull 35:443–457

    Article  PubMed  Google Scholar 

  10. Englisch S, Esser A, Enning F et al (2010) Augmentation with pregabalin in schizophrenia. J Clin Psychopharmacol 30:437–440

    Article  PubMed  CAS  Google Scholar 

  11. Englisch S, Knopf U, Scharnholz B et al (2009) Duloxetine for major depressive episodes in the course of psychotic disorders: an observational clinical trial. J Psychopharmacol 23:875–882

    Article  PubMed  CAS  Google Scholar 

  12. Fleischhacker WW, Heikkinen ME, Oli JP et al (2008) Weight change on aripiprazole-clozapine combination in schizophrenic patients with weight gain and suboptimal response on clozapine: 16-week double-blind study. Eur Psychiatry 23:114–115

    Article  Google Scholar 

  13. Genc Y, Taner E, Candansayar S (2007) Comparison of clozapine-amisulpride and clozapine-quetiapine combinations for patients with schizophrenia who are partially responsive to clozapine: a single-blind randomized study. Adv Ther 24:1–13

    Article  PubMed  CAS  Google Scholar 

  14. Goodwin G, Fleischhacker W, Arango C et al (2009) Advantages and disadvantages of combination treatment with antipsychotics, ECNP Consensus Meeting, March 2008, Nice. Eur Neuropsychopharmacol 19:520–532

    Article  PubMed  CAS  Google Scholar 

  15. Honer WG, Thornton AE, Chen EY et al (2006) Clozapine alone versus clozapine and risperidone with refractory schizophrenia. N Engl J Med 354:472–482

    Article  PubMed  CAS  Google Scholar 

  16. Jaeger M, Messer T, Laux G et al (2008) Standardized remission criteria in schizophrenia: descriptive validity and comparability with previously used outcome measures. Pharmacopsychiatry 41:190–195

    Article  Google Scholar 

  17. Leucht S, Kissling W, McGrath J (2007) Lithium for schizophrenia. Cochrane Database Syst Rev:CD003834

    Google Scholar 

  18. Leucht S, Kissling W, McGrath J et al (2007) Carbamazepine for schizophrenia. Cochrane Database Syst Rev:CD001258

    Google Scholar 

  19. McEvoy JP, Lieberman JA, Stroup TS et al (2006) Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 163:600–610

    Article  PubMed  Google Scholar 

  20. McGurk SR, Twamley EW, Sitzer DI et al (2007) A meta-analysis of cognitive remediation in schizophrenia. Am J Psychiatry 164:1791–1802

    Article  PubMed  Google Scholar 

  21. Meyer-Lindenberg A, Weinberger DR (2006) Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nat Rev Neurosci 7:818–827

    Article  PubMed  CAS  Google Scholar 

  22. Paton C, Whittington C, Barnes TR (2007) Augmentation with a second antipsychotic in patients with schizophrenia who partially respond to clozapine: a meta-analysis. J Clin Psychopharmacol 27:198–204

    Article  PubMed  CAS  Google Scholar 

  23. Pickar D, Vinik J, Bartko JJ (2008) Pharmacotherapy of schizophrenic patients: preponderance of off-label drug use. PLoS ONE 3:e3150

    Article  PubMed  Google Scholar 

  24. Poyurovsky M, Fuchs C, Pashinian A et al (2007) Attenuating effect of reboxetine on appetite and weight gain in olanzapine-treated schizophrenia patients: a double-blind placebo-controlled study. Psychopharmacol 192:441–448

    Article  CAS  Google Scholar 

  25. Schwarz C, Volz A, Li C et al (2008) Valproate for schizophrenia. Cochrane Database Syst Rev:CD004028

    Google Scholar 

  26. Sepehry AA, Potvin S, Elie R et al (2007) Selective serotonin reuptake inhibitor (SSRI) add-on therapy for the negative symptoms of schizophrenia: a meta-analysis. J Clin Psychiatry 68:604–610

    Article  PubMed  CAS  Google Scholar 

  27. Taylor DM, Smith L (2009) Augmentation of clozapine with a second antipsychotic – a meta-analysis of randomized, placebo-controlled studies. Acta Psychiatr Scand 119:419–425

    Article  PubMed  CAS  Google Scholar 

  28. Tiihonen J, Lonnqvist J, Wahlbeck K et al (2009) 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 374:620–627

    Article  PubMed  Google Scholar 

  29. Tiihonen J, Wahlbeck K, Kiviniemi V (2009) The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis. Schizophr Res 109:10–14

    Article  PubMed  Google Scholar 

  30. Os J van, Kapur S (2009) Schizophrenia. Lancet 374:635–645

    Article  PubMed  Google Scholar 

  31. Weinbrenner S, Assion HJ, Stargardt T et al (2009) Drug prescription patterns in schizophrenia outpatients: analysis of data from a German health insurance fund. Pharmacopsychiatry 42:66–71

    Article  PubMed  CAS  Google Scholar 

  32. Zink M, Englisch S, Meyer-Lindenberg A (2010) Polypharmacy in schizophrenia. Curr Opin Psychiatry 23:103–111

    Article  PubMed  Google Scholar 

  33. Zink M, Kuwilsky A, Krumm B et al (2009) Efficacy and tolerability of ziprasidone versus risperidone as augmentation in patients partially responsive to clozapine: A randomized controlled clinical trial. J Psychopharmacol 23:305–314

    Article  PubMed  CAS  Google Scholar 

  34. Zisook S, Kasckow JW, Golshan S et al (2009) Citalopram augmentation for subsyndromal symptoms of depression in middle-aged and older outpatients with schizophrenia and schizoaffective disorder: a randomized controlled trial. J Clin Psychiatry 70:562–571

    Article  PubMed  CAS  Google Scholar 

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Interessenskonflikte

Der korrespondierende Autor weist auf folgende Beziehungen hin: M.Z. erhielt wissenschaftliche Projektförderung, Vortragshonorare und Kongressunterstützung von der Deutschen Forschungsgemeinschaft (DFG), ERAB (European Research Advisory Board), Pfizer Pharma, Bristol-Myers Squibb, Astra Zeneca, Eli-Lilly und Janssen Cilag. S.E. erhielt Kongressunterstützung und Honorare für Beratertätigkeit von AstraZeneca, Bristol-Myers Squibb and Otsuka Pharma, Eli-Lilly, Janssen Cilag, Lundbeck und Pfizer Pharma. A.M.-L. erhielt Beraterhonorare und Kongressunterstützung von AstraZeneca, Hoffmann-La Roche, Lundbeck Foundation, ferner Vortragshonorare von Pfizer Pharma, Lilly Deutschland, Glaxo SmithKline, Janssen Cilag, Bristol-Myers Squibb, Lundbeck und AstraZeneca.

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Authors and Affiliations

  1. Abteilung fürf Psychiatrie and Psychotherapie, Zentralinstitut für seelische Gesundheit, 68072, Mannheim, Deutschland

    M. Zink, S. Englisch & A. Meyer-Lindenberg

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  1. M. Zink
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  2. S. Englisch
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  3. A. Meyer-Lindenberg
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Correspondence to M. Zink.

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Zink, M., Englisch, S. & Meyer-Lindenberg, A. Polypharmazie bei schizophrenen Psychosen. Nervenarzt 82, 853–858 (2011). https://doi.org/10.1007/s00115-010-3196-0

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