Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment.

The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant-dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs.

[Drug monitoring of antipsychotics and antidepressants during acute admission in a psychiatric state hospital in Germany]. / Prästationäres Drug-Monitoring von Psychopharmaka bei Akutaufnahme in einer psychiatrischen Versorgungsklinik.

In the treatment of affective and schizophrenic psychosis, modern atypical antipsychotic agents and newer antidepressive agents recently have increasingly been used. In this prospective naturalistic study, patients were examined who had previously been treated psychopharmaceutically for a schizophrenic (n = 52) or depressive (n = 38) disorder and were readmitted in a psychiatric emergency clinic. While Serum levels were examined major interest was to find out similarities or differences in the drug compliance of schizophrenic and depressive patients before rehospitalization.

[Determining serum concentrations of the modern antipsychotic quetiapin: clinical relevance in therapeutic drug monitoring]. / Die klinische Relevanz der Serumspiegeluntersuchung des modernen Antipsychotikums Quetiapin im Rahmen eines Therapeutischen Drug-Monitorings.

OBJECTIVE: The results concerning therapeutic drug monitoring of Quetiapin concentration in 152 in-patients will be presented. METHOD: In addition to measuring the serum concentration of Quetiapin standardized patient data were collected and the clinical history assessed by the Brief Psychiatric Rating Scale (BPRS). RESULTS: A significant positive correlation of the serum concentration and the daily dosage was found. Co-medication with the CYP 3A4 inhibitor Nefazodon was associated with an increase in the serum concentration without any adverse interactions occurring. CONCLUSION: While a correlation of dosage and effect could be shown with Quetiapin, inter- and intraindividual differences could be observed. Drug monitoring therefore seems useful in clinical setting and is recommended.

[Management of the atypical antipsychotic olanzapine in a clinical environment with particular regard to therapeutic drug monitoring (TDM) in a German State hospital]. / Zum Umgang mit dem modernen atypischen Neuroleptikum Olanzapin im klinischen Alltag unter besonderer Berücksichtigung des Therapeutischen Drug-Monitorings (TDM) an einer psychiatrischen Versorgungsklinik.

OBJECTIVE: Therapeutic drug monitoring (TDM) has been established at BKH Augsburg (psychiatric district hospital) since January 2001. According to Olanzapine product information the following illustration shows the evaluation (n = 216) of various parameters of the TDM requirements of Olanzapine. METHODS: Items examined include "classification according to diagnoses", "reason for requirement", "severity of disease", "therapeutic effect" and "side-effects". In addition, serum concentration, daily dosage, clinical assessment (Brief Psychiatric Rating Scale), age, height and weight of patients will be presented. RESULTS: Clearly sick patients, 52 % of them between 20 and 30 years old, were less compliant and achieved only a moderate therapeutic effect. CONCLUSIONS: TDM is mainly assessed to control compliance. However, more specific and more personalized TDM would be more useful.