Zur Pathophysiologie der Gewichtsregulation im Rahmen der Therapie mit Psychopharmaka

 

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Zusammenfassung:

Gewichtsveränderungen unter psychopharmakologischer Therapie sind seit langem bekannt und werden seit den 50er Jahren erforscht. Sie treten überwiegend in Form von Gewichtszunahmen auf. Die klinische Relevanz ergibt sich zum einen aus einer erhöhten allgemeinen Morbiditätsrate und zum anderen aus einer Gefährdung der Therapie-Compliance. Gewichtsanstiege finden sich bei Patienten während der Behandlung mit Psychopharmaka unterschiedlichster chemischer Struktur und aus den verschiedensten Substanzklassen. Als Ursachen werden schon lange Medikamenteneffekte auf verschiedene Neurotransmitter-Systeme, insbesondere blockierende Wirkungen auf Serotonin- und Histamin-Rezeptoren, diskutiert. Erst in den letzten Jahren wird zunehmend erforscht, welche Rolle endokrine Faktoren spielen. Hierbei zeichnet sich eine besonders wichtige Rolle für das im Fettgewebe produzierte Hormon Leptin ab, welches dem zentralen Nervensystem die Größe der peripheren Fettspeicher signalisiert, und das wohl die entscheidende periphere Regelgröße für die langfristige Gewichtsregulierung darstellt. Darüber hinaus deuten jüngste Befunde darauf hin, dass auch Immunmediatoren, und unter diesen insbesondere das proinflammatorische Zytokin Tumornekrosefaktor-α (TNF-α) und die löslichen TNF-Rezeptoren, an psychopharmaka-induzierten Veränderungen von Appetit und Gewicht ursächlich beteiligt sind. Veränderungen des TNF-Systems treten sogar schon deutlich vor der Gewichtszunahme auf, so dass ihnen eventuell ein prädiktiver Wert zukommt. Die Möglichkeiten zur Prophylaxe und Therapie psychopharmaka-induzierter Gewichtsanstiege umfassen einerseits psychotherapeutische und andererseits medikamentöse Maßnahmen. Zwar existiert eine Reihe strukturierter verhaltenstherapeutischer Programme, die gut zur Gewichtsreduktion geeignet sind, aber insbesondere bei schwer kranken psychiatrischen Patienten sind sie oft von nur geringgradiger Effizienz. Bezüglich der möglichen pharmakologischen Interventionen zeichnen sich vielversprechende Ansätze dadurch ab, dass in den letzten Jahren sowohl zentral als auch peripher wirksame Medikamente zur Gewichtsreduktion in die Klinik eingeführt wurden; allerdings liegen zu ihrer Verwendbarkeit im Bereich psychiatrischer Erkrankungen und zur Frage der pharmakokinetischen und pharmakodynamischen Interaktion mit Psychopharmaka bisher keine ausreichenden Daten vor.

On the Pathophysiology of Weight Regulation During Treatment with Psychotropic Drugs:

Weight changes during pharmacological treatment are a well-known phenomenon and they have been an object of research since the 1950's. Weight gain occurs during treatment with drugs of different chemical structures and is an important problem when patients are treated with antidepressants, antipsychotics, or mood stabilizers. The clinical relevance of drug-induced weight changes is due to increased rates of morbidity and reduced treatment compliance. Regarding the underlying causes, the important role of neurotransmitter systems and in particular the blockade of serotonin and histamine receptors has been discussed since decades. Only recently, however, research has been started on the effects of psychotropic agents on major neuroendocrine systems involved in appetite and weight regulation. These studies suggest that the fat-cell derived hormone leptin might play an important role. Leptin signals to the brain the size of the adipose tissue and is probably the most important peripheral signal for the long-term regulation of weight. In addition to the neuroendocrine systems, weight gain induced by psychotropic agents might also involve immune modulators, in particular the proinflammatory cytokine tumor-necrosis-factor-α (TNF-α) and soluble TNF-receptors. Some psychotropic agents influence the TNF system very rapidly, already prior to any obvious increases in weight. Hence, changes in the TNF-α system might be of predictive value for drug-induced weight gain. Strategies to minimize or to counteract weight gain induced by psychotropic agents include psychotherapeutic and pharmacological approaches. Although numerous psychotherapeutic approaches are available, they are only of limited usefulness in severely ill psychiatric patients. Fortunately, a number of promising pharmacological approaches to reduce weight have been introduced into clinical practice during the last years; however, so far there is no knowledge on pharmacodynamic and -kinetic interactions with psychotropic drugs, and there is no clinical data on the usefulness and safety of such drug combinations.

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PD Dr. med T Pollmächer

Max-Planck-Institut für Psychiatrie

Kraepelinstr. 10
80804 München

Email: E-mail: topo@mpipsykl.mpg.de