Kombination von Antidepressiva – eine sinnvolle Behandlungsstrategie bei therapieresistenten Depressionen?

Zusammenfassung

Die folgende Arbeit fasst Nutzen und Risiken der bisher bekannten Kombinationsbehandlungen mit Antidepressiva bei therapieresistenten Depressionen zusammen. Die Literaturrecherche erfolgte mittels einer Medline-Datenbank-Recherche der Jahrgänge 1990 – 2006. Kombinationstherapien zweier Antidepressiva werden im klinischen Alltag sehr häufig durchgeführt. Sinnvolle Antidepressivakombinationen nutzen den Vorteil komplementärer Wirkmechanismen, um einen synergistischen Nutzen zu erzielen. Vorteile einer Kombinationstherapie bestehen in der Fortführung einer partiellen Response auf eine Monotherapie und dem gleichzeitig damit verbundenen Vermeiden der Gefahr einer Verschlechterung depressiver Symptome durch Absetzen des partiell wirksamen Antidepressivums. Nachteile dieser Strategie bestehen in dem Risiko von Arzneimittelwechselwirkungen, einer möglichen Potenzierung von unerwünschten Arzneimittelwirkungen und höheren Behandlungskosten. Obwohl Kombinationsstrategien in der klinischen Praxis oft angewandt werden, gibt es nur wenig kontrollierte Studien, um ihren Nutzen und ihre Wirksamkeit zu belegen (Evidenzlevel C, dies trifft auf alle Kombinationstherapien zu). Wichtig erscheint darauf hinzuweisen, dass die Zugabe eines SSRI zu einem Trizyklikum einen erhöhten Blutspiegel und eine verzögerte Metabolisierung des Trizyklikums herbeiführen kann, was eventuell ein erhöhtes Toxizitätsrisiko der trizyklischen Medikation nach sich führt. Die Kombination eines irreversiblen MAO-Hemmers mit Clomipramin, einem SSRI oder einem SSNRI sollte aufgrund eines möglichen Serotonin-Syndroms grundsätzlich vermieden werden.

Die detaillierte Kenntnis der dargestellten Kombinationsstrategien ermöglicht unter Umständen bessere Behandlungsergebnisse bei therapieresistenten Depressionen.

Abstract

Various pharmacological strategies have been developed to treat such refractory depression, of which combination therapies with antidepressants are one of the most important. This article reviews both benefits and risks of all known antidepressant combination strategies. The relevant literature was identified by means of a computerized MEDLINE research on the years 1990 – 2006 and scanning of review articles. The use of antidepressant combinations to overcome refractory depression is a common strategy in practice. Many antidepressants can be usefully combined especially if they engage separate mechanisms of action – like SSRIs with Reboxetine, Bupropion, Mirtazapine and Tricyclics – or on the other hand – Tricyclics with MAO-Inhibitiors. Combination strategies are effective treatment options, however they do have potential safety risks due to pharmacokinetic and pharmacodynamic interactions. Combinations including MAOIs can cause serotonin syndrome, and some SSRIs like Fluoxetine may elevate tricyclic plasma levels with the consequence of an increased risk of toxicity. The distinct knowledge of available antidepressant combination strategies may help to increase response – as well as remission rates in therapy resistant depression. However, further research is urgently needed to determine relative efficacy.

Schlüsselwörter

Antidepressiva - therapieresistente Depression - Kombinationen von Antidepressiva - Antidepressivanonresponse

Key words

antidepressants - therapy resistant depression - refractory depression - combination therapies with antidepressants

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