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Antidepressiva zur Behandlung der Depression bei Palliativpatienten

Eine systematische Literaturübersicht

Antidepressants for treatment of depression in palliative patients

A systematic literature review

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Zusammenfassung

Hintergrund

Die Therapie der Depression bei Palliativpatienten erfordert die Abwägung des erwarteten Nutzens und Schadens von Antidepressiva (AD) bei ggf. kurzer Lebenserwartung, reduziertem Allgemeinzustand, fortgeschrittenem Alter und erhöhtem Risiko für Nebenwirkungen und Medikamenteninteraktionen. Die vorliegende systematische Übersicht stellt die Evidenz zur Wirksamkeit und Verträglichkeit unterschiedlicher Wirkstoffklassen in Abhängigkeit von der Art und Schwere der Grunderkrankung dar.

Methode

Es wurde eine systematische Datenbanksuche (Medline und EMBASE) nach klinischen Studien durchgeführt und die Literaturverzeichnisse der identifizierten relevanten Literatur gesichtet. Für den Einschluss mussten Patienten eine im Suchstring definierte Erkrankung (wie multiple Sklerose, Morbus Parkinson, Alzheimer-Demenz, HIV/AIDS, Krebs, COPD, Herzinsuffizienz) aufweisen. Berücksichtigt wurden Studien, welche die Wirksamkeit von AD im Vergleich mit Placebo, einem anderen AD, einem Benzodiazepin, Psychostimulans oder einer Psychotherapie geprüft hatten. Im 1. Schritt wurden nur Studien an Patienten eingeschlossen, deren Depression mittels etablierter Diagnosekriterien diagnostiziert wurden und bei denen die Veränderung der Depression als primärer Endpunkt erhoben wurde. In einem 2. Schritt wurden auch Studien eingeschlossen, die die beiden letztgenannten Kriterien nicht erfüllten, aber Patienten am Lebensende untersuchten.

Ergebnisse

Vierzig Studien (die vorwiegend von SSRI oder NSMRI einsetzten) wurden eingeschlossen. Sechzehn Studien untersuchten Antidepressiva bei neurologischen, 24 bei internistischen Erkrankungen. Neun Studien untersuchten Patienten am Lebensende bzw. in weit fortgeschrittenen Erkrankungsstadien. Aus den heterogenen Studiendesigns lässt sich nicht ableiten, inwieweit Wirksamkeit und Verträglichkeit der AD von der Krankheitsschwere abhängig sind. Die Studien waren für die Erhebung begrenzter Behandlungseffekte vermutlich häufig zu klein. Dass AD gerade in den größeren Studien nicht wirksamer als Placebo waren, weist auf einen möglichen Publikationsbias hin. Bei den internistischen Erkrankungen stehen sich zumeist heterogene Ergebnisse gegenüber. Entgegen der gern geübten Verordnungspraxis verweisen die Studienergebnisse bei Alzheimer-Demenz auf fehlende Wirksamkeit der SSRI. Bei Morbus Parkinson liegen nur Studien an kleinen Populationen vor, sodass aus dem fehlenden Nachweis der Überlegenheit von SSRI in der Mehrzahl der Studien nicht sicher auf das Fehlen eines Effektes geschlossen werden kann.

Schlussfolgerung

Die Übersicht über die Datenlage erlaubt nur begrenzte Rückschlüsse für den Einsatz von AD bei unterschiedlichen körperlichen Erkrankungen am Ende des Lebens. Eindeutige Konsequenzen für die Behandlung mit AD in Abhängigkeit von der Schwere der Grunderkrankung oder im Vergleich mit anderen Behandlungsoptionen (Psychotherapie, Benzodiazepine etc.) können aus den eingeschlossenen Studien nicht direkt abgeleitet werden.

Abstract

Background

Treatment of depression in palliative care must take into account expected benefits and risks of antidepressants in patients with potentially limited life expectancy, poor medical condition, advanced age and higher risk to suffer from side effects and drug interactions. This systematic review assesses evidence of the efficacy and safety of different classes of antidepressants depending on the type and severity of the physical illness.

Methods

A systematic database search (Medline, EMBASE) for clinical studies was carried out and references of identified literature were checked. To be included in the review studies had to be performed in illnesses that were part of in the search strategy, such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, HIV/AIDS, cancer, COPD and heart failure. Considered were controlled studies comparing the efficacy of antidepressants to placebo, other classes of antidepressants, benzodiazepines, psychostimulants or psychotherapy. In a first step only studies with patients meeting established diagnostic criteria of depression and where depression was a primary endpoint were included. In a second step, additional studies were included that did not meet both of the latter criteria but were performed in patients at the end of life.

Results

A total of 40 trials (mostly using SSRI or NSMRI) were included, 16 studies were performed in neurological, 24 in general medical conditions and 9 studies were performed in patients at the end of life or in advanced disease stages. Due to heterogeneous study designs no conclusions can be drawn if efficacy or tolerability is dependent on disease severity. In most cases, studies might have been too small to detect limited treatment effects. As a lack of efficacy was predominantly shown in larger trials, publication bias might have been present. In most of the reviewed general medical conditions study results were heterogeneous. In contrast to the popularity of the treatment approach, results suggest that SSRIs are not effective in Alzheimer’s disease. In Parkinson’s disease, negative studies are too small to prove lack of efficacy of SSRIs as present in the majority of trials.

Conclusions

This review of the evidence allows only limited conclusions concerning the use of antidepressants in physical illness disorders at the end of life. The reviewed evidence does not allow direct conclusions to be drawn concerning the use of antidepressants in different disease severities and its benefits compared to other treatment options (psychotherapy, benzodiazepines etc.). The English full text version of this article will be available in SpringerLink as of November 2012 (under “Supplemental”).

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Abb. 1

Abbreviations

↑↑/↓↓:

positive/negative Aussage sehr gut belegt

↑/↓:

positive/negative Aussage gut belegt

(↑)/(↓):

Hinweis für positive/negative Aussage

↔:

hinreichende Belege für Aussage fehlen

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Danksagung

Die Arbeit wurde nach den Vorgaben der Steuerungsgruppe der „Empfehlungen zur Therapie in der Palliativmedizin“ der Arzneimittelkommission der deutschen Ärzteschaft (Lukas Radbruch, Friedemann Nauck, Bernd Alt-Epping, Roman Rolke, Mariam Ujeyl, Rainer Lasek) und ohne externe Förderung durchgeführt. Die Autoren danken Frau Prof. Stoppe, Basel, für die kritische Kommentierung eines ersten Manuskriptes.

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  1. Arzneimittelkommission der deutschen Ärzteschaft, Geschäftsstelle, Herbert-Lewin-Platz 1, 10623, Berlin, Deutschland

    M. Ujeyl & B. Müller-Oerlinghausen

  2. Charité Universitätsmedizin, Berlin, Deutschland

    B. Müller-Oerlinghausen

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  1. M. Ujeyl
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Ujeyl, M., Müller-Oerlinghausen, B. Antidepressiva zur Behandlung der Depression bei Palliativpatienten. Schmerz 26, 523–536 (2012). https://doi.org/10.1007/s00482-012-1221-x

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