Regensburg, Univ., Diss., 2009.

Derzeit gibt es nur wenige Informationen zu konzentrationsabhängigen klinischen Effekten von Clozapin und Olanzapin in der Behandlung von Kindern und Jugendlichen mit schizophrenen Störungen. Es existieren keine altersspezifisch-definierte therapeutische Zielbereiche für die Höhe der Serumkonzentration in dieser Altersklasse. Das Ziel dieser retrospektiven, naturalistischen Studie ist die Untersuchung der Zusammenhänge zwischen Dosis, Serumkonzentration und klinischen Effekten (Therapieeffekt und unerwünschte Arzneimittelwirkungen) sowie die Untersuchung möglicher Einflussfaktoren darauf. Des Weiteren sollen Erkenntnisse zu therapeutischen Konzentrationsbereichen von Clozapin und Olanzapin bei Kindern und Jugendlichen gewonnen werden. Ausgewertet wurden multizentrische Daten von 32 (Clozapin) bzw. 17 (Olanzapin) Patienten, bei denen routinemäßig Therapeutisches Drug Monitoring im Zeitraum von Februar 2004 bis Dezember 2007 durchgeführt wurde. Die psychopathologische Befundeinschätzung erfolgte mittels der Clinical Global Impression Scale und der Brief Psychiatric Rating Scale, die der unerwünschten Arzneimittelwirkungen mithilfe der Dose Record and Treatment Emergent Symptom Scale bzw. der Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. Bei beiden untersuchten Wirkstoffen zeigte sich eine signifikant positive Korrelation zwischen der (gewichtskorrigierten) Tagesdosis und der Serumkonzentration sowie eine hohe interindividuelle Variabilität der Serumkonzentrationen bei gleicher Dosierung. Als weiterer möglicher Einflussfaktor auf die Höhe der Serumkonzentration konnte in der Olanzapin-Stichprobe eine signifikante Assoziation zwischen dem Geschlecht und der Serumkonzentration nachgewiesen werden: Mädchen scheinen unter gleicher klinischer Dosierung höhere Serumkonzentrationen aufzubauen als Jungen. In beiden Stichproben gab es eine hohe Rate dokumentierter unerwünschter Arzneimittelwirkungen. Ein Zusammenhang zwischen der Höhe der Serumkonzentration und dem Auftreten unerwünschter Arzneimittelwirkungen ließ sich nicht nachweisen. In der Clozapin-Stichprobe zeigte sich ein signifikanter Zusammenhang zwischen der Serumkonzentration und dem Therapieeffekt: Im untersuchten Sample war der Therapieeffekt besser bei niedrigeren (< 350 ng/ml) Serumkonzentrationen. Zudem zeigte sich eine Tendenz zu einem niedrigeren unteren Schwellenwert für einen empfohlenen therapeutischen Bereich der Serumkonzentration verglichen mit dem Bereich der für Erwachsene definiert wurde. In der Olanzapin-Stichprobe ließ sich mit dem gewählten Studiendesign keine signifikante Korrelation zwischen der Serumkonzentration und dem Therapieeffekt nachweisen. Die Mehrheit der pädiatrischen Patienten hatte eine Serumkonzentration innerhalb des empfohlenen Zielbereichs für Erwachsene. Dieses Ergebnis könnte auf eine Übereinstimmung des zu empfehlenden Zielbereichs der Serumkonzentration von Olanzapin in beiden Altersklassen hinweisen. Aufgrund der Limitationen des naturalistischen Studiendesigns sind weitere Studien mit kontrolliertem Design und größerer Stichprobe notwendig, um die Ergebnisse zu replizieren. / There is limited information on the concentration-dependent clinical effects of clozapine and olanzapine in the treatment of children and adolescents with schizophrenic disorders and age-specific therapeutic target ranges of serum concentrations in this age group are not defined yet. The aim of this retrospective, naturalistic study was to investigate the relationship between daily dose, serum concentrations and clinical outcome (positive therapeutic effects and adverse drug reactions) of clozapine and olanzapine in child and adolescents and finally, to investigate any factors influencing these relationships. Furthermore, it should be examined whether the recommended therapeutic concentration ranges for adults are also valid for children and adolescents. Data from 32 (clozapine) and 17 (olanzapine) patients were routinely collected between February 2004 and December 2007. Psychopathological findings were assessed using the Clinical Global Impression Scale and the Brief Psychiatric Rating Scale. Adverse drug reactions were assessed via the Dose Record and Treatment Emergent Symptom Scale and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. For both substances investigated, a significant positive correlation was found between the (weight-corrected) daily dose and the serum concentration. Furthermore, a high interindividual variability of the serum concentrations at the same dose was observed. For olanzapine treated individuals, a significant association was found between gender and serum concentration: females were found to have higher serum concentrations than males at the same clinical dose. There was a high rate of documented adverse drug reactions for both substances. However, a correlation between the level of serum concentration and the occurrence of adverse drug reactions could not be demonstrated. In the clozapine sample, there was a significant correlation between the serum concentration and the therapeutic effect: In the investigated sample, the therapeutic effect was better at lower (<350 ng/ml) serum concentrations. In addition, results hint on a lower threshold for a recommended therapeutic range of serum concentration compared to the range defined for adults. In the olanzapine sample, with the selected study design a significant correlation between the serum concentration and the therapeutic effect was not shown. The majority of pediatric patients had serum concentrations within the recommended range for adults. This result hints on concordant recommended serum concentration ranges in both age groups. Due to the limitations of the naturalistic study design, further studies with controlled design and larger sample size are needed to verify and replicate the results.

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Background: Anorexia nervosa is known as an eating disorder that is associated with significant low body-weight, self-starvation and food restrictions. It all usually starts with thoughts of a desire wanting to eat healthier and look thinner. The sickness has become increasingly common in the recent time where 0,5-1% of Sweden’s population suffers from the disease. Most of those who suffer from anorexia nervosa are young girls in their teenage years.The disease comes with consequences and needs to be treated. A person sick in anorexia nervosa can feel a loss of strength which is associated with the lack of energy. Other symptoms that come along with anorexia nervosa are usually low blood pressure, low pulse (bradycardia) and amenorrhea.Anorexia nervosa is an eating disorder, but it also has psychological effects that often come with depression and obsessive-compulsive disorder. These symptoms combined makes it difficult to treat anorexia nervosa and usually demands a combination of supervised weight gain and psychological therapy. Objective: The aim of this study was to evaluate the efficacy of olanzapine treatment regarding weight gain in patients suffering from anorexia nervosa. Olanzapine is an atypical antipsychotic drug that has a well-known adverse effect known as weight gain. In this study this adverse effect of olanzapine is used to see if the drug can be well tolerated and applied to patients suffering from anorexia nervosa. Method: This literature review study analyzed six studies and their results regarding the efficacy of olanzapine on weight gaining in anorexia nervosa patients. One study that was included in this literature review was a case study of a young 15-year-old girl's journey to become healthy from anorexia nervosa while using olanzapine. Three of the six studies were randomized controlled trials that compared olanzapine against placebo while two of the six studies were open label studies that evaluated olanzapine efficacy in anorexia nervosa patients. Results: The results based on the six studies show that olanzapine has positive effects regarding weight gaining in patients suffering low weight from anorexia nervosa. The randomized controlled trials that were included in this literature review study show that olanzapine had a greater significant effect on weight gain compared to placebo. The side effects of olanzapine presented in the studies were very mild to moderate and included sleepiness and headache. The doses of olanzapine used in the six studies were similar and contained 10-15 mg olanzapine each day. Conclusion: In summary, olanzapine has the benefit of increasing weight in anorexia nervosa patients, but the evidence is limited because of the small number of participants in the studies and only a few studies have been made. It would be of interest to see if olanzapine still has a beneficial effect in larger studies with more participants.

Psychotropic drugs are commonly used group of pharmaceuticals, their main effect is to alter psychic condition, including mental diseases treatment. Symptoms of mental illnesses are more and more common, theref orenumber of patients diagnosed with mental illnes, and thus using psychotropics, is growing stronger. But using psychotropics during gestation is not without risks for mother and embryo itself. However, thanks to the absence of controlled human studies, the knowledge of emrbyotoxic effects of pschotropics is limited to casuistics, reported side effects and animal experimental studies. Many of those studies suggests emrbyotoxic potential of psychotropic drugs, on the other hand, others claim their safety. The goal of this thesis is to test at least some of them, using CHEST method, that allows us to observe direct effect of unmetabolized substance on chick embryo. In this thesis we tested selected psychotropics, very common antidepressant fluoxetine (prozac) and antipsychotic drug olanzapine, for embryotoxicity, using in ovo method CHEST with chick embryos as model organism. By bypassing the maternal organism and his metabolism, this method allows to observe direct effect of unmetabolized substance on chick embryo. Results revealed embryotoxic effect of fluoxetin in dosage 10-2 and 10-3 on 3rd and...

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