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Biomedical subjects

W W Fleischhacker

Publications and source records attributed to W W Fleischhacker.

At least 19 recordsLinked to original sources
PubMed2006

[Pharmacotherapy for schizophrenia].

The management of schizophrenia patients remains one of the great challenges in psychiatry. Despite the undisputed effectiveness of antipsychotic drugs, patients and their physicians still face considerable difficulties mainly related to incomplete or lacking treatment response and the inability to predict the individual efficacy and tolerability. In this manuscript we review the key elements of pharmacological treatment of this disorder, encompassing acute and long-term management as well as specific management problems ranging from acutely violent patients to treatment-resistant subjects. Along with general treatment principles, the document provides specific information regarding efficacy and safety features of antipsychotics. Many of the currently available treatment recommendations/guidelines are based on the evidence reviewed here. This review is meant to serve as a guide for clinicians involved in managing schizophrenia, whether in a psychiatric hospital setting or as family physicians in private practice.

Acute Disease↗
PubMed2005

Olanzapine impairs glycogen synthesis and insulin signaling in L6 skeletal muscle cells.

Second-generation antipsychotic agents (SGAs) are increasingly replacing first-generation antipsychotic agents due to their superior activity against the negative symptoms of schizophrenia, decreased extrapyramidal symptoms and better tolerability. However, some SGAs are associated with adverse metabolic effects as significant weight gain, lipid disorders and diabetes mellitus. The pathogenesis of SGA-induced disturbances of glucose homeostasis is unclear. In vivo studies suggest a direct influence of SGAs on peripheral insulin resistance. To this end, we analyzed whether olanzapine might alter glycogen synthesis and the insulin-signaling cascade in L6 myotubes. Glycogen content was diminished in a dose- and time-dependent manner. Within the insulin-signaling cascade IRS-1 tyrosine phosphorylation was induced several fold by insulin and was diminished by preincubation with olanzapine. IRS-1-associated PI3K activity was stimulated by insulin three-fold in L6 myotubes. Olanzapine inhibited insulin-stimulated IRS-1-associated PI3K activity in a dose-dependent manner. Protein mass of AKT, GSK-3 and GS was unaltered, whereas phosphorylation of AKT and GSK-3 was diminished, and pGS was increased. Finally, we compared olanzapine with amisulpride, an SGA clinically not associated with the induction of diabetes mellitus. Glycogen content was diminished in olanzapine-preincubated L6 cells, whereas this effect was not observed under the amisulpride conditions. We conclude that olanzapine impairs glycogen synthesis via inhibition of the classical insulin-signaling cascade and that this inhibitory effect may lead to the induction of insulin resistance in olanzapine-treated patients.

Animals↗
PubMed2005

[Pathophysiology of schizophrenia and its impact on pharmacotherapy].

Schizophrenia is a severe psychiatric illness with a lifetime morbidity risk of around 1 %. Symptoms include hallucinations, delusions, poverty of thought and emotion and social withdrawal and cognitive deficits. Although newer antipsychotics affecting multiple neurotransmitter receptors facilitate therapy, many patients still do not achieve full response. Despite intensive study, the molecular etiology of schizophrenia remains enigmatic in many ways. The dopamine hypothesis of schizophrenia still plays an important role, although pharmacological studies, brain imaging analyses and genetic research indicate additional dysfunctions of glutamate, GABA and serotonin transmission. This article reviews the pathophysiological background of the disorder, its implications for pharmacological treatment and possible directions for future research.

Antipsychotic Agents↗
PubMed2003

Brain activation pattern during a verbal fluency test in healthy male and female volunteers: a functional magnetic resonance imaging study.

Sex differences in executive speech tasks, favoring women, have been noted in behavioral studies and functional imaging studies. In the present study ten female and ten male volunteers underwent functional magnetic resonance imaging in a conventional block design. All subjects were selected on the basis of high performance on the verbal fluency task. Regions of activation were detected after performance of a covert lexical verbal fluency task inside the scanner. Men and women who did not differ significantly in verbal fluency task performance showed a very similar pattern of brain activation. Our data argue against genuine between-sex differences in cerebral activation patterns during lexical verbal fluency activities when confounding factors like performance differences are excluded.

Adult↗
PubMed2003

Sex differences in brain activation pattern during a visuospatial cognitive task: a functional magnetic resonance imaging study in healthy volunteers.

Sex differences in mental rotation tasks, favoring men, have been noted in behavioral studies and functional imaging studies. In the present study ten female and ten male volunteers underwent functional magnetic resonance imaging in a conventional block design. Regions of activation were detected after performance of a mental rotation task inside the scanner. In contrast to previous studies, confounding factors such as performance differences between genders or high error rates were excluded. Men showed significantly stronger parietal activation, while women showed significantly greater right frontal activation. Our results point to gender specific differences in the neuropsychological processes involved in mental rotation tasks.

Brain↗
PubMed2003

New developments in the pharmacotherapy of schizophrenia.

This review summarizes current key research strategies and the most prominently pursued new potential treatments for schizophrenia. First, new routes of administration for second generation antipsychotics are presented. These include rapidly dissolving tablets, drops and sirups as well as new intramuscular formulations. Newly available short acting and long acting (depot) antipsychotics complement oral antipsychotics so that the full spectrum of routes of administration is now available for second generation antipsychotics. Next to antipsychotic polypharmacy, in which two or more antipsychotics are combined, pharmacological add-on treatments, mainly with benzodiazepines, antidepressants and mood stabilizers enjoy increasing popularity. Most of this practice is driven by personal preferences, clinical experience and marketing rather than evidence based medicine. New pharmacological mechanisms currently utilized in advanced states of development include partial dopamine D2-receptor agonism, supplementation with glutamatergic agents, estrogen and omega-3-fatty acids. While the concept of partial D1-agonism has already led to the successful launch of a new antipsychotic, aripiprazole, the other attempts to improve therapeutic response in schizophrenia patients have so far provided equivocal results. It is argued that they may be helpful for certain subgroups or specific symptoms of schizophrenia patients. In conclusion, many exciting new pharmacological leads are currently pursued and this will very likely augment the options for treating patients with schizophrenia.

Antipsychotic Agents↗
PubMed2002

Differential diagnosis of depressed mood in patients with schizophrenia: a diagnostic algorithm based on a review.

OBJECTIVE: To review the available literature on depressive symptomatology in schizophrenia in order to establish a diagnostic algorithm of depressive syndromes in schizophrenia. METHOD: A literature search was performed using PubMed and Medline. Additional information was gained by cross-referencing from papers found in the database. Data from controlled studies as well as supplementary information from review articles and psychiatric manuals pertinent to the topic were used. Depressive symptoms were classified with respect to their temporal relationship to acute psychotic symptoms before the background of nosological entities as operationalized by Diagnostic Statistical Manual IV (DSM IV). RESULTS: Depression is a common and devastating comorbid syndrome in patients suffering from schizophrenic disorder. The paper summarizes the relevant diagnostic steps to guide the clinician towards therapeutic interventions, which differ depending on the nature of the depressive syndrome. CONCLUSION: Differentiating depressives states in schizophrenia has consequences in terms of choosing therapeutic strategies. An algorithm which leads the practitioner to a reliable diagnosis and in consequence to a valid therapy is presented.

Algorithms↗
PubMed2002

The impact of hemoglobin levels on fatigue and quality of life in cancer patients.

BACKGROUND: Although fatigue is a commonly reported symptom in cancer patients its etiology is still poorly understood. The objective of the present study was to investigate the relationship between hemoglobin (Hb) levels and the subjective experience of fatigue and quality of life in cancer patients with mild or no anemia undergoing chemotherapy. PATIENTS AND METHODS: Sixty-eight cancer patients (25 colorectal, 26 lung and 17 ovarian cancer) presently undergoing chemotherapy participated in the study. Fatigue was measured with the Multidimesional Fatigue Inventory (MFI-20), quality of life with The European Organization for Research and Treatment of Cancer QLQ-C30. In order to provide normative data for fatigue levels, the MFI-20 was also completed by a sex- and age-matched sample of 120 healthy controls. RESULTS: Compared with healthy subjects, cancer patients experienced significantly higher levels of subjective fatigue. Correlations between Hb values and subscales of the MFI-20 were moderate with a tendency to increase during chemotherapy. Hb values alone, however, do not fully account for the observed fatigue. Other symptoms, especially pain, dyspnea and sleep disturbances, also showed an association with perceived fatigue. CONCLUSIONS: Despite significant correlations, these results indicate that Hb values only partially explain subjectively experienced fatigue and quality of life in cancer patients. It is suggested therefore that the treatment of fatigue must be multidimensional and involve all areas which contribute to the syndrome.

Adult↗
PubMed2001

Use of alternative/complementary therapy in breast cancer patients--a psychological perspective.

The objectives of this study were to assess the additional use of alternative (complementary) therapies in patients with breast cancer who were receiving conventional treatment and to compare patients using alternative therapies with patients receiving only conventional treatment with special reference to psychological adaptation, causal attribution and quality of life. A sample of 117 female out-patients with a diagnosis of breast cancer filled in the following assessment instruments: FQCI (Freiburg Questionnaire for Coping with Illness), PUK (Causal Attribution Questionnaire), EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire), POMS (Profile of Mood States), and a self-developed questionnaire on alternative therapies. Nearly half the patients (47%, n = 55) reported that they had used alternative therapies in addition to conventional treatment. The methods applied most frequently were nutrition-related measures (special drinks, vitamin preparations and whole-foods - each applied by about 50% of users), mistletoe preparations (49%), trace elements (47%), and homeopathy (31%). Compared with patients receiving only conventional treatment, the users of alternative therapy were younger and better educated. Users developed a more active style of illness coping than nonusers and showed more religious involvement. Patients using a large number of alternative therapies (>3) tended to adopt a more depressive coping style than those using only a small number (< or =3). For a substantial proportion of cancer patients alternative therapies apparently fulfil an important psychological need. However, a subgroup of patients using many alternative therapies seem to have considerable adjustment problems. In dealing with cancer patients the treatment team should be aware of both these groups.

Adaptation, Psychological↗
PubMed2001

Differential regulation of chromogranin A, chromogranin B and secretogranin II in rat brain by phencyclidine treatment.

Chromogranin A, chromogranin B and secretogranin II belong to the chromogranin family which consists of large protein molecules that are found in large dense core vesicles. Chromogranins are endoproteolytically processed to smaller peptides. This study was designed to elucidate the regulation of chromgranin expression by acute and subchronic phencyclidine administration. The behavioral syndrome produced by phencyclidine represents a pharmacological model for some aspects of schizophrenia [Jentsch and Roth (1999) Neuropsychopharmacology 20, 201-225]. Tissue concentrations of chromogranins were measured with specific radioimmunoassays. Alterations in secretogranin II gene expression were investigated by in situ hybridization. A single dose of phencyclidine (10mg/kg) led to a transient decrease in secretoneurin tissue levels in the prefrontal cortex after 4h followed by an increase in secretoneurin tissue levels after 12h. Repeated phencyclidine treatment (10mg/kg/day) for five days resulted in elevated secretoneurin levels in cortical areas whereas chromogranin A and chromogranin B tissue levels were unchanged. After the same treatment, a significant increase in the number of secretoneurin containing neurons was found in cortical layers II-III, and V-VI as revealed by immunocytochemistry. The increases in secretoneurin levels were paralleled by an increased number of secretogranin II messenger RNA containing neurons as well as by an increased expression of secretogranin II by individual neurons. The present study shows that secretoneurin II tissue concentration and secretogranin II messenger RNA expression is distinctly altered after acute and subchronic phencyclidine application. From these results we suggest that phencyclidine may induce synaptic alterations in specific brain areas and may contribute to a better understanding of synaptic dysfunction which may also occur in schizophrenia.

Animals↗
PubMed2001

Quality of life measurement in oncology--a matter of the assessment instrument?

Two widely used quality of life questionnaires, European Organization for Research and Treatment of Cancer Core (EORTC QLQ-C30) & Functional Assessment of Cancer Therapy-General (FACT-G), were examined for their comparability using four different groups of cancer patients. During a follow-up investigation, 418 cancer patients (Hodgkin's disease, breast cancer, bone marrow transplantation (BMT), chronic lymphatic leukaemia (CLL)) completed both the EORTC QLC-C30 and the FACT-G during the same session. For an illustration of the differences between the two Quality of Life (QoL) instruments, pairs of diagnostic groups were formed and their QoL scores using the EORTC QLQ-C30 and FACT-G compared. The corresponding subscales of the EORTC-QLC-C30 and the FACT-G show only low to moderate intercorrelations across all four groups of cancer patients studied. In particular, a comparison of pairs, namely Hodgkin's disease versus breast cancer patients and BMT versus CLL patients, highlights substantial differences in the corresponding subscales of the EORTC QLQ-C30 and the FACT-G. The results of the QoL investigations should not be interpreted independently of the instrument used and an interpretation of results must be based on the contents of items of the respective questionnaires.

Adult↗
PubMed2001

A qualitative assessment of the neurological safety of antipsychotic drugs; an analysis of a risperidone database.

BACKGROUND: Neurological side effects of antipsychotic agents limit the use of these drugs, and development of newer antipsychotic agents has been focused on a reduced risk of extrapyramidal symptoms (EPS) as well as effective symptom control. METHODS: A qualitative analysis of EPS was performed using Extrapyramidal Symptom Rating Scale (ESRS) data from 11 double-blind risperidone trials. An ESRS factor analysis and maximum changes in ESRS scores were compared for the risperidone, haloperidol, and placebo groups. RESULTS: The factor analysis revealed five factors. Between-group comparisons showed no differences between placebo and 1 to 2 mg/day-risperidone groups. Parkinsonism, tremor, akathisia, and sialorrhea were more likely to occur with haloperidol than with placebo or risperidone at 1 to 6 mg/day. Similar results were noted by maximum changes in ESRS scores. At risperidone doses of more than 8 mg/day, acute EPS severity lay between that of the placebo and haloperidol groups. The severity of tardive dyskinesia was greater in patients receiving placebo than in those receiving either active treatment. CONCLUSIONS: As the results described above were derived from a post hoc analysis of an existing database, conclusions must remain tentative. To provide more definitive answers, EPS assessments in future studies should be refined to more accurately predict the type of EPS expected with a given agent in clinical practice.

Adolescent↗
PubMed2001

Association of olanzapine-induced weight gain with an increase in body fat.

OBJECTIVE: The goal of this study was to explore the pathophysiology of weight gain during treatment with olanzapine for schizophrenia. METHOD: The authors used a prospective, controlled, open study comparing body weight, body mass index, and related biological measures in mentally and physically healthy volunteers and olanzapine-treated patients with schizophrenia. Weight, eating behavior, leptin serum levels, body mass index, and body composition were assessed over an 8-week observation period. RESULTS: A significant increase in body weight, leptin serum levels, and percentage of body fat was seen in patients treated with olanzapine, but the drug-free comparison group did not show any significant changes. The weight gain during antipsychotic treatment with olanzapine was mainly attributable to an increase in body fat; patients' lean body mass did not change. CONCLUSIONS: In addition to the original finding that an increase in body fat is mainly responsible for olanzapine-induced weight gain, these findings confirm results obtained in other studies showing increases in body weight and serum leptin levels during treatment with second-generation antipsychotics.

Adipose Tissue↗
PubMed2001

The clinical implications of weight gain in schizophrenia.

The tendency of most of the second generation antipsychotics to induce weight gain to a larger extent than that of traditional neuroleptics has renewed the interest in weight problems of patients with schizophrenia. Drug-induced weight gain has been identified as a major risk factor for various medical disorders that might be responsible for the increased morbidity and mortality rates of patients suffering from schizophrenia. Also, it has a major impact on compliance. This article focuses on the clinical relevance of increased body weight in schizophrenia. It outlines screening and management options to prevent and/or manage weight gain associated with schizophrenia in everyday clinical practice. The first strategies should be to identify obesity-prone patients at the beginning of treatment and provide information (to patients and caregivers) about the risks of weight gain and its consequences. Additionally, the possibility of weight gain calls for a regular monitoring of weight and weight-related laboratory parameters. The patients should also be offered dietary advice as well as regular exercise and behavior modification programs. Physicians must be aware of the problem of weight gain associated with schizophrenia and choose antipsychotic medication carefully, especially in patients at high risk for weight gain.

Adult↗
PubMed2000

Further evidence that behavioral tests and neuropeptide mRNA and tissue level alterations can differentiate between typical and atypical antipsychotic drugs.

This study was designed to compare some behavioral and biochemical effects of chronic treatment with a range of antipsychotic drugs. Gene expression of enkephalin, chromogranin A, chromogranin B, and secretogranin II and their respective peptide products were studied with in situ hybridization and radioimmunoassays after daily oral administration of haloperidol, clozapine, risperidone, or zotepine for 21 days. In behavioral tests, significant catalepsy was induced by haloperidol only. All four antipsychotic drugs increased hind paw retraction time but only haloperidol also increased forelimb retraction time. In the caudate putamen, haloperidol increased both enkephalin mRNA expression and enkephalin tissue levels. Neither of these parameters was altered by the other three drugs. In the prefrontal cortex, antipsychotic drugs generated a distinct pattern of gene expression in two regards. First, the dopamine D(2) receptor antagonist, haloperidol, did not significantly alter synaptic protein levels or their encoding mRNAs. Secondly, there was a differential change in tissue levels and mRNA expression since secretogranin II was not affected by any tested antipsychotic drug. This study shows that different types of antipsychotic drug induce distinct behavioural effects as well as differential changes in the biosynthesis of synaptic proteins and their encoding mRNAs. The data reinforce the notion that haloperidol can be classed as a typical antipsychotic drug whilst clozapine, zotepine, and risperidone reflect their atypical classification.

Animals↗