Zusammenfassung
Risperidon, ein sehr potenter Serotonin-Dopamin-Antagonist, wurde 1984 zum erstenmal synthetisiert. Die Phase-1-Studien begannen 1985, offene Phase-2-Versuche wurden 1986 eingeleitet. Diese Studien erbrachten den Hinweis, daß Risperidon im Dosisbereich von 5–10 mg möglicherweise eine therapeutische Wirkung auf positive, negative und affektive Symptome der Schizophrenie zuzuschreiben ist; weiterhin induziert es nur eine geringe extrapyramidale Symptomatik und besitzt eine ausgezeichnete allgemeine Verträglichkeit.
Das Phase-3-Programm, in das mehr als 2300 Patienten einbezogen waren, sollte zur Bestätigung dieses klinischen Profils dienen. Verschiedene Versuchsanordnungen wurden angewendet, alle Versuche waren doppelblind, randomisiert und gegen ein Referenzpräparat kontrolliert. Zwei Versuche waren sowohl plazebo- als auch referenzkontrolliert. Es wurde sowohl mit flexiblen als auch mit festen Dosisansätzen gearbeitet. Die Bewertung basierte auf der PANSS (Positive and Negative Syndrom Scale for Schizophrenia), der Clinical Global Impression und der ESRS (Extrapyramidale Symptom Rating Scale). Dieses Phase-3-Programm zeigte die Überlegenheit von Risperidon gegenüber Haioperidol in Dosierungen zwischen 4 und 8 mg pro Tag, und zwar sowohl im Hinblick auf positive und negative Symptome als auch für allgemeine psychopathologische Symptome nach Definition der PANSS. Risperidon-Dosen bis 8 mg induzierten signifikant weniger extrapyramidale Symptome als Haioperidol, und risperidonbehandelte Patienten benötigten signifikant weniger Anti-parkinsonmittel als haloperidolbehandelte Patienten. Besonders Akathisie und akute Dystonie, die gravierendsten extrapyramidalen Symptome, wurden, im Gegensatz zu Haloperidol, unter allen Risperidondosierungen sehr selten beobachtet. Die Daten über mehr als 200 Patienten weisen darauf hin, daß dieses therapeutische Profil bei Lanzeitverarbreichung erhalten bleibt.
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Summary
Risperidone — a summary of the clinical results. Risperidone, a very potent serotonin-dopamine antagonist, was first synthetized in 1984. Phase I studies started in 1985 and open phase II trials were initiated in 1986. These studies indicated that risperidone in a dose range of 5–10 mg had a potential therapeutic effect on positive, negative and affective symptoms of schizophrenia, a low EPS inducing profile, and an excellent overall tolerability.
The Phase III programme, which included more than 2300 patients, was designed to confirm this clinical profile. Different trial designs were applied: all trials were double-blind, randomized, reference drug controlled. Two trials were both placebo- and reference drug controlled. Both flexible dose and fixed dose approaches were used. The evaluation was based on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Clinical Global Impression and the Extrapyramidal Symptom Rating Scale (ESRS). This Phase III programme showed that risperidone, in dosages between 4 to 8 mg daily, is superior to haloperidol as well for positive symptoms, negative symptoms as for general psychopathology symptoms defined according to the PANSS. Risperidone doses up to 8 mg induced significantly less EPS than haloperidol, and risperidone treated patients required significantly less EPS antiparkinson medication than haloperidol treated patients. Especially akathisia and acute dystonia, the most disturbing ectrapyramidale symptoms, were, in contrast with haloperidol, very rarely seen with any dose of risperidone. Data on more than 200 patients indicate that this therapeutic profile is maintained in longterm follow-up.
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Heylen, S.L.E. (1993). Combined serotonin 5-HT2 and dopamine D2 antagonism in the treatment of schizophrenia: clinical results with risperidone. In: Platz, T. (eds) Brennpunkte der Schizophrenie. Aktuelle Probleme der Schizophrenie, vol 4. Springer, Vienna. https://doi.org/10.1007/978-3-7091-9285-6_26
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