Biomedical subjects

E Rüther

Publications and source records attributed to E Rüther.

At least 19 recordsLinked to original sources

PubMed2006

Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin.

Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N=39) with defined cognitive deficit (>or=1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40,000 IU rhEPO (N=20) or placebo (N=19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) - perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.

Adult↗

PubMed2006

CSF diagnosis of Alzheimer's disease and dementia with Lewy bodies.

Differential diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) is often crucial. CSF Tau protein and Amyloid-beta (A beta) peptides have shown diagnostic value for the diagnosis of AD, but discrimination from DLB was poor.Herein, we investigate CSF of 18 patients with probable AD, 25 with probable DLB and 14 non-demented disease controls (NDC) by A beta-SDS-PAGE/immunoblot and commercially available ELISAs for A beta1-42 and tau. CSF A beta peptide patterns and tau exhibited disease specific alterations among AD and DLB. The ratio of A beta1-42 to A beta1-38 and A beta1-42 to A beta1-37, respectively, in combination with absolute tau, yielded a sensitivity and specificity of 100 and 92%, respectively. We conclude that CSF A beta peptide patterns and tau levels reflect disease-specific pathophysiological pathways of these dementias as distinct neurochemical phenotypes. Combined evaluation of these biomarkers provides a reasonable accuracy for differential diagnosis of AD and DLB.

Aged↗

PubMed2006

[Anxiety disorders: long-term treatment and replapse prevention].

Anxiety disorders show a tendency to become chronic. Behavioral treatment and pharmacotherapeutic measures must frequently be applied over a lengthy period of time. The most suitable drugs for long-term treatment are the selective serotonin reuptake inhibitors (SSRI) and the serotonin norepinephrine reuptake inhibitor (SNRI), venlafaxine. With regard to side effects, the specific characteristics of the anti-anxiety drugs used for long-term therapy must be taken into account.

Anti-Anxiety Agents↗

PubMed2005

Evaluation of oxidative stress measurements in obstructive sleep apnea syndrome.

Assessment of reactive oxygen species (ROS) is highly important in neurodegenerative disorders and neuroleptic treatment. However, conflicting results have been reported, which may arise from methodological difficulties. Obstructive sleep apnea (OSA) syndrome with episodic hypoxia-reoxygenation is proposed as a human model for the investigation of ROS measurements. Despite a broad analytical approach comprising lipid peroxidation and amino acid oxidation products, oxidative DNA damage, and activity of the antioxidant defense, only plasma malondialdehyde (MDA) and urinary o,o'-dityrosine seemed to be appropriate, robust biomarkers of oxidative stress, which are also simple enough for routine clinical use. MDA concentrations correlated with a duration of nocturnal desaturation below 85% (r = 0.77, p<0.0005), and o,o'-dityrosine levels decreased after therapy (p<0.05) as a function of baseline concentrations (r = -0.61, p<0.05). Gender effects in ROS generation also have to be considered. At present, we recommend the application of several oxidative stress measurements at different time points, preferably involving plasma MDA and urinary o,o'-dityrosine.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2005

[Selective serotonin and noradrenaline reuptake inhibitors: a step forward in the treatment of depression?].

With the tricyclics, selective serotonin reuptake inhibitors (SSRIs) and other substances, we now have available a range of medications for the treatment of depression and other psychological disorders (e.g. anxiety, panic). Nevertheless, only some of the patients experience a remission of their depressive symptoms. The occurrence of side effects and the only modest level of effectiveness result in inadequate compliance on the part of the patient. With venlafaxine and duloxetine two representatives of the selective serotonin and noradrenaline reuptake inhibitor (SSNRI) class of antidepressants are now available. SSNRIs have a dual effect coupled with high selectivity. The present article the extent to which this particular action mechanism results in an improved clinical efficacy and tolerability profile of the SSNRIs, in particular in comparison with SSRIs.

Antidepressive Agents↗

PubMed2005

[Pharmacotherapy in personality disorders].

Subjects with personality disorders represent a relevant subset of the clinical psychiatric population and, to an even bigger extent, a comorbid condition to an axis-I diagnosis. Personality disorders appear to be difficult to treat and problematic in the therapeutic setting, and a pharmacologic treatment often does not follow recommendations from empirical studies. Psychopharmacologic drugs are able to modify the expression of certain personality dimensions, which are mainly disorder-related variables of temperament. Modern pharmacotherapy of personality disorders has a neurobiological basis. This is underlined by evidence from animal studies and can be associated with certain receptor-specific functions in humans. Treatment is consequently symptom-related and not specific for any disorder. It must be stressed that certain features but not the entire personality can be modified by drug treatment. Data from drug studies are still relatively scarce. An overview of studies on personality disorders is presented including information on dosages and augmenting strategies. Psychotherapy still is the basic treatment for personality disorders. However, psychopharmacological interventions should not only be considered when psychotherapy has failed. Treatments should be complementary from the start. There is a rationale for short- and long-term treatment. The latter is indicated, despite of the scarcity of data, when longer lasting and severe affective symptoms emerge. Response rates vary among the trials and appear to be lower than in non-comorbid axis-I disorders. A treatment algorithm is presented.

Anticonvulsants↗

PubMed2005

Pseudohallucinations associated with moclobemide: a case report.

The goal of the multicenter drug surveillance project AMSP ("Arzneimittelsicherheit in der Psychiatrie") is the monitoring, assessment and analysis of adverse drug reactions (ADR) of psychopharmalogical drugs. We report about a 23 year-old patient with a depressive episode. He developed severe pseudohallucinations under a treatment with moclobemide. The symptoms occur 6 days after starting the medication and decline within two days after stopping moclobemide. The term "pseudohallucinations" is discussed controversially but still of high interest.

Adult↗

PubMed2005

Prescribing practices in German and Swiss psychiatric university and in non-university hospitals: national differences.

OBJECTIVE: There are great variations between hospitals in the way drugs are prescribed, and these variations may be due to multiple factors such as local prescribing traditions, pharmacoeconomic considerations, drug availability, regional differences of population, disease prevalence etc. Available studies on prescribing habits, apart from studies performed in a unique center, have until now been mainly restricted to single countries or regions and the comparisons across countries or regions have often been limited by the use of diverse methodologies and definitions. The aim of the present study was to compare drug prescriptions between German and Swiss psychiatric services with regard to their preference of newer psychotropics. MATERIAL AND METHODS: Five psychiatric hospitals, associated to the AMSP project, were chosen to represent Swiss and German clinics, university and non-university settings. Data were available from one index day on 572 patients and 1,745 prescriptions. The comparisons were adjusted for age and gender. RESULTS: There was a significant difference (p < 0.001) with regard to the prescription of newer antidepressants (NAD), Swiss clinicians giving proportionally more (65.2%) than the German psychiatrists (48.3%). No significant difference was, on the other hand, found as to the proportion of atypical antipsychotics, the lack of difference being due to the higher proportion of clozapine among the atypical antipsychotics in Germany. CONCLUSION: There seems, therefore, to be a higher propensity for Swiss hospital psychiatrists to prescribe newer antidepressants. This seems to be due to national or regional prescribing traditions. Further studies are needed to investigate the economical influences on antidepressant prescribing in Swiss and German clinics.

Adolescent↗

PubMed2004

[Considerations in the combination of clozapine and benzodiazepines].

Serious adverse events and even sudden death have been reported during administration of the combination of clozapine and benzodiazepines. However, this combination does not necessarily result in increased frequency of serious adverse events. Thus it is not regarded as an absolute contraindication and might be useful in distinct clinical situations, e.g., during the occurrence of a malignant neuroleptic syndrome, "catatonic dilemma," or severe agitation during clozapine treatment. In the following report, certain suggestions on how to deal with this combination therapy are provided which may provide a basis for discussion that ultimately may lead to the formulation of guidelines for this combination therapy. Such guidelines may help psychiatrists in dealing with this combination in clinical situations. Moreover, the formulation of such guidelines would help with forensic issues in case of serious adverse events occurring during this combination therapy.

Adverse Drug Reaction Reporting Systems↗

PubMed2004

CPAP-therapy effectively lowers serum homocysteine in obstructive sleep apnea syndrome.

Assessment of serum total homocysteine (tHcy) in patients with obstructive sleep apnea (OSA) syndrome is highly relevant since both are strongly associated with stroke and cognitive dysfunction. Seven of 16 untreated OSA patients showed tHcy levels exceeding 11.7 micromol/l. The circadian pattern of serum tHcy in untreated and treated patients (p < 0.001) implied a diagnostic impact of blood sampling time. Treatment with continuous positive airway pressure (CPAP) effectively lowered tHcy levels in patients by about 30% (p < 0.005) and thus probably the (hyper)homocysteinemia-related cognitive dysfunction and the risk for cardio-/cerebrovascular diseases.

Chromatography, High Pressure Liquid↗

PubMed2004

Erythropoietin: a candidate compound for neuroprotection in schizophrenia.

Erythropoietin (EPO) is a candidate compound for neuroprotection in human brain disease capable of combating a spectrum of pathophysiological processes operational during the progression of schizophrenic psychosis. The purpose of the present study was to prepare the ground for its application in a first neuroprotective add-on strategy in schizophrenia, aiming at improvement of cognitive brain function as well as prevention/slowing of degenerative processes. Using rodent studies, primary hippocampal neurons in culture, immunohistochemical analysis of human post-mortem brain tissue and nuclear imaging technology in man, we demonstrate that: (1) peripherally applied recombinant human (rh) EPO penetrates into the brain efficiently both in rat and humans, (2) rhEPO is enriched intracranially in healthy men and more distinctly in schizophrenic patients, (3) EPO receptors are densely expressed in hippocampus and cortex of schizophrenic subjects but distinctly less in controls, (4) rhEPO attenuates the haloperidol-induced neuronal death in vitro, and (4) peripherally administered rhEPO enhances cognitive functioning in mice in the context of an aversion task involving cortical and subcortical pathways presumably affected in schizophrenia. These observations, together with the known safety of rhEPO, render it an interesting compound for neuroprotective add-on strategies in schizophrenia and other human diseases characterized by a progressive decline in cognitive performance.

Adult↗

PubMed2004

The AMSP drug safety program: methods and global results.

The AMSP (Arzneimittelsicherheit in der Psychiatry) study is a drug safety program that ensures the continuous assessment of severe adverse drug reactions (ADR) in psychiatric inpatients under the natural conditions of routine clinical treatment. It developed out of the preceding drug surveillance study AMUP (Arzneimittelüberwachung in der Psychiatrie). Currently 35 hospitals participate in the study. This paper describes the methods of the AMSP, gives detailed definitions of ADRs assessed to be "severe," and discusses the implications of these definitions and the methodological approach for evaluating the AMSP data. In addition, some overall data compiled on ADR rates from 1993 to 2000 are given.

Adverse Drug Reaction Reporting Systems↗

PubMed2004

Research methods in drug surveillance.

Adverse drug reactions must be monitored, beginning with the development of a new drug, and continuing throughout its complete life cycle. During these various stages, different methods are necessary. This paper describes the advantages and disadvantages of common methods of collecting data on adverse drug reactions after a drug has been approved. We then concentrate on two drug surveillance projects, the Prescription Event Monitoring (PEM) of the Drug Surveillance Research Unit and the AMSP Project ("Arzneimittelsicherheit in der Psychiatrie", Drug Safety in Psychiatry). AMSP is compared to cohort studies and spontaneous reporting systems on the one hand, and the specialised PEM project, on the other. The possible influence of various sources of bias is critically analysed.

Adverse Drug Reaction Reporting Systems↗

PubMed2004

The AMUP study for drug surveillance in psychiatry - a summary of inpatient data.

From 1979 to 1989 the AMUP study (AMUP = Arzneimittelüberwachung in der Psychiatrie) was conducted in two psychiatric hospitals in Germany with the aim to provide a systematic and standardized assessment of all adverse reactions to psychotropic drugs under conditions of routine practice. A total of 60.7 % of patients experienced at least one adverse drug reaction (ADR) with probable or definite causality during their stay in the hospital; 37.1 % of patients exhibited ADRs that had some therapeutic impact on further treatment. ADRs that led to drug discontinuation were observed in 8.6 %. This rate ranged from 9.5 to 5.1 % for haloperidol and perazine, the most common neuroleptics at that time; sedating antidepressants (AD) rated lower than non-sedating (amitriptyline 5.1 %, clomipramine 10.4 %). Lithium salts, antiparkinson drugs, and benzodiazepines were associated with considerably lower rates of ADRs than neuroleptics or antidepressants. Severe ADRs occurred in 1.4 % of exposed patients (e. g., toxic delirium, grand mal seizures, malignant neuroleptic syndrome, or agranulocytosis). The AMUP data suggest that administration of psychotropic drugs in psychiatric hospitals at that time was a safe, but also inconvenient treatment for many patients due to a wide range of bothersome side effects that compromised patient compliance. The data can serve as a reference base for comparisons with newer compounds introduced to the market over the last decade such as serotonin reuptake inhibitors (SSRIs) and other new AD, atypical neuroleptics, or other new generation psychotropic drugs.

Adverse Drug Reaction Reporting Systems↗

PubMed2004

Psychotropic drug use in psychiatric inpatients: recent trends and changes over time-data from the AMSP study.

A considerable number of new drugs were introduced over the last few years. In this report we analyze to what extent they have come to be used in clinical practice and what changes in drug use have resulted from the availability of the new compounds. For this purpose, data on drug use in 1995 and 2001 assessed at two reference days per year and per hospital within the drug safety program AMSP were compared for 10 hospitals that had been participating in both years. Atypical neuroleptics (NL) were used in 59.9 % of patients on NLs in 2001 (16.7 % in 1995), most frequently olanzapine, risperidone, clozapine, and quetiapine, in this order. Thirty-nine percent of patients still received typical NLs in antipsychotic indication (77.1 % in 1995), and 30.8 % received typical hypnosedative NLs (38.1 % in 1995). SSRIs, other new ADs, and TCAs were used in similar rates in 2001, i. e., in 40.5 %, 37.9 %, and 34.8 % of AD patients, respectively (1995 : 24.2 %, 6.2 %, and 72.3 %, respectively). Mirtazapine was the most common AD in 2001, followed by citalopram, sertraline, and doxepin. Hypnotics were prescribed more frequently in 2001 (17.6 % vs. 11.7 %), mostly BZD agonists at that time, whereas overall anxiolytic use (in approximately 30 %) hardly changed over time. Mood stabilizers and anti-dementia drugs were given comparatively rarely, even in pertinent diagnoses. Polypharmacy was observed in about three-quarters of patients on psychotropic drugs, with a trend towards increasing use over time. Combinations of two NLs, of NL + AD, and of NLs + anxiolytic were most common in both years. Twenty percent of patients on atypical NLs received typical antipsychotic NLs additionally; typical hypnosedative NLs were used along with typical antipsychotics and atypical NLs in 20 % and 22 % of patients, respectively. TCAs and either SSRIs or other new ADs were still the most common AD combinations in 2001. Data were also analyzed according to the main diagnostic categories.

Adolescent↗

PubMed2004

Severe adverse drug reactions of antidepressants: results of the German multicenter drug surveillance program AMSP.

The goal of the German drug safety program in psychiatry AMSP (Arzneimittelsicherheit in der Psychiatrie) is the assessment of severe or new adverse drug reactions (ADRs). Here we report on 53,042 of 122,562 patients treated with antidepressants who were monitored from 1993 to 2000 in 35 psychiatric hospitals in German-speaking countries. The overall incidence of severe ADRs of antidepressants was 1.4 % of exposed patients; when only ADRs rated as probable or definite were considered, a rate of 0.9 % in patients treated with antidepressants was observed. ADR rates were higher for TCAs (imputed in 1.0 % of patients overall, respectively in 0.6 % of patients when only ADs were imputed) and lower for MAO inhibitors and SSRIs (0.7 % for both, respectively 0.3 % and 0.4 %). Within the TCA group there was a difference among clomipramine (2.1 %, respectively 1.0 %), amitriptyline (1.0 %, respectively 0.6 %), and doxepin or trimipramine (both 0.6 %, respectively 0.3 %). With regard to single SSRI, similar rates were observed for paroxetine (0.8 %, respectively 0.5 %) and for citalopram (0.7 %, respectively 0.4 %). Of the new dual-acting antidepressants, venlafaxine ranged at 0.9 %, (respectively 0.5 %) and mirtazapine at 0.6 % (respectively 0.5 %). In particular, TCAs were associated with known risks, such as toxic delirium, grand mal seizures, and hepatic (i. e., increased liver enzymes), urologic (i. e., urinary retention), allergic (i. e., exanthema), or cardiovascular (i. e., mainly orthostatic collapse) reactions. In SSRI-treated patients (non-delirious) psychic and neurological ADRs were most prominent, followed by gastrointestinal, dermatologic, and endocrinological/electrolyte reactions, with agitation, hyponatremia (probably as part of the SIADH syndrome and associated with severe neurologic or psychiatric symptoms in 64 % of all cases), increased liver enzymes, nausea, and the serotonin syndrome as leading unwanted symptoms. Venlafaxine (in the immediate-release formulation) was associated with adverse CNS and somatic symptoms such as severe agitation, diarrhea, increased liver enzymes, hypertension, and hyponatremia. Mirtazapine was mostly connected with increased liver enzymes, cutaneous edema, and collapse, but with no case of significant hyponatremia. For drugs that potently inhibit serotonin uptake, serum sodium concentration should be controlled when applied in high-dose therapy or in vulnerable patients.

Adult↗

PubMed2004

Severe adverse drug reactions in psychiatric inpatients treated with neuroleptics.

Numerous studies compare side effects or adverse drug reactions (ADRs) of the various typical and newer atypical neuroleptics in patients with schizophrenia. However, these studies, as controlled randomized trials, represent an artificial setting of drug administration and do not easily relate to the "real-life" setting of psychiatric treatment. In contrast, the AMSP drug safety program allows the monitoring of ADRs of all types of psychopharmacological agents in the naturalistic setting of routine clinical practice. In the present study, the data on neuroleptics acquired in the AMSP program from 1993 to 2000 are analyzed. In this period, 86,439 patients treated with at least one neuroleptic agent were monitored. In 1.1 % of the patients severe ADRs occurred. In contrast to the results from controlled trials, atypical neuroleptics caused more severe ADRs than did typical neuroleptics. This result was mainly caused by the high number of severe ADRs in patients treated with clozapine and concerned delirium and non-EPS neurological, gastrointestinal, hepatic, dermatological, hematological, and endocrinological ADRs. Atypical neuroleptics were found to be superior in EPS and urological ADRs. Excluding the data on clozapine, we found typical and atypical neuroleptics to be similar in the occurrence of severe ADRs, although the profiles differ between these two groups as well as between the single substances. Our findings provide valuable information on the type and frequency of ADRs in psychiatric practice, thus enabling differential indication of neuroleptics based not only on the efficacy and tolerability data of controlled trials but also on their differential ADR profile occurring in the "real-life" setting of routine clinical treatment.

Adult↗

PubMed2004

Severe and uncommon involuntary movement disorders due to psychotropic drugs.

Disorders of involuntary movement due to psychotropic drugs pose a major problem when treating mentally ill patients. These adverse drug reactions (ADR) frequently undermine the patients' compliance and may have serious consequences as well. The drug safety program in psychiatry AMSP (Arzneimittelsicherheit in der Psychiatrie) surveyed a population of 122,562 patients between 1993 and 2000, and documented 129 especially severe or uncommon involuntary movement disorders (IMD): 9 episodes of severe acute dyskinesia, 32 of severe Parkinsonism, 5 of especially severe akathisia, 16 of 'atypical dyskinesia', 38 of Pisa syndrome, 6 of catatonic neuroleptic syndrome, 15 of neuroleptic malignant syndrome, and 8 of tardive dyskinesia. The epidemiological data for this population were systematically analyzed as regards the patient's history of medication, comedication, and clinical course. In those cases, in which a certain drug was imputed to cause an ADR alone and the causal relationship was rated as definite or probable, typical neuroleptics with mainly antipsychotic effects showed a relatively high incidence of 0.1047 %, those with hypnotic-sedative effect a lower incidence of 0.0198 %, and the atypical neuroleptics an incidence of 0.0567 %. This difference was highly significant in an chi (2)-analysis (chi (2) = 18.81, df = 2, p < 0.0001). Our data provide important information on the frequency, severity, and the consequences of ARD for the patients' compliance, and thus are of clinical interest.

Adult↗