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Biomedical subjects

H Wetzel

Publications and source records attributed to H Wetzel.

At least 19 recordsLinked to original sources
PubMed1992

Risperidone in the treatment of disorders with a combined psychotic and depressive syndrome--a functional approach.

In vitro receptor-binding profiles and in vivo pharmacological studies have shown risperidone to be a potent mixed serotonin-S2 dopamine-D2-like receptor antagonist. While anti-D2 activity may relate to the antipsychotic potency of neuroleptic drugs, an antidepressive efficacy of substances with anti-S2 activity has been suggested. In an open pilot-study, ten patients with schizodepressive disorders or a DSM-III-R diagnosis of psychotic major depressive episodes were treated with risperidone (2-10 mg/d) for six weeks. Weekly psychopathological evaluation was performed, including BPRS, SANS, SAPS, VAS scales, and AIMS and UKU for the assessment of side-effects. Generally, the psychotic syndrome (BPRS, SANS and SAPS) decreased markedly in all patients; seven patients also showed a clinically significant improvement of depressive symptoms (BPRS). Except for two patients who needed biperiden because of extrapyramidal side-effects, the tolerance of risperidone was good. The antipsychotic and antidepressive properties of risperidone shown in our pilot study are promising enough to merit full double-blind controlled trials for further evaluation of its therapeutic value in this broad spectrum of psychiatric disorders.

Adult↗
PubMed1992

Dopamine autoreceptor agonists in the treatment of schizophrenia and major depression.

Dopamine autoreceptor agonists reduce the firing rate, synthesis, and release of dopamine in dopaminergic neurons by means of a negative feedback mechanism via stimulation of autoreceptors. Moreover, dopamine autoreceptor agonists are able to stimulate supersensitive but not normosensitive postsynaptic receptors. For dopamine autoreceptor agonists, therapeutic effects by readjustment of excessive or deficient dopaminergic function have been postulated for positive and negative schizophrenic symptomatology as well as for subtypes of depressive disorders. Investigations on the therapeutic effects of autoreceptor-nonselective dopamine agonists in schizophrenia or depression have yielded inconsistent results. In order to reduce the excess of central dopaminergic activity postulated by the dopamine hypothesis of schizophrenia, dopamine autoreceptor agonists have been tested in open clinical trials in positive schizophrenic symptomatology. However, administration of selective dopamine autoreceptor agonists like talipexole or roxindole did not result in a significant improvement of positive psychotic symptoms. In negative schizophrenic symptomatology, a dopamine deficit rather than an excess has been hypothesized. Current evidence from pilot studies suggests that dopamine autoreceptor agonists like roxindole may produce a minor to moderate improvement of symptoms like affective flattening, depressed mood, alogia, and avolition, possibly by stimulation of supersensitive postsynaptic dopamine receptors. For certain subgroups of depression, a reduction of functional dopamine activity has been postulated. In an open pilot study in patients with a major depression, roxindole demonstrated antidepressive properties comparable to those of standard antidepressants, justifying further double-blind controlled trials against reference drugs.

Animals↗
PubMed1992

Automated determination of fluvoxamine in plasma by column-switching high-performance liquid chromatography.

A column-switching system with high-performance liquid-chromatographic separation and ultraviolet detection is described for automated determination of fluvoxamine in human plasma or serum. Samples were injected and the drug was retained in a clean-up column [20 x 4.6 mm (i.d.)] filled with C8 reversed-phase material (10-micron particles). After unwanted material was washed out, the drug was eluted and separated with an analytical chromatography column, 4.6 x 250 mm (i.d.), filled with Nucleosil 100 CN (5-micron particles) with an acetonitrile:methanol:0.01 mol/L phosphate buffer eluent (188:578:235 by vol) at a flow rate of 1.5 mL/min for < 20 min and detected by spectrometry at 214 nm. With oxaprotiline as internal standard, fluvoxamine could be easily quantified, and it was well separated from endogenous plasma constituents and various psychoactive drugs. The detection limit was 10 micrograms/L (31.6 nmol/L), the analytical recoveries were 97-100%, and the relationship between drug concentration and detector response was linear from 0 to 1000 micrograms/L (3160 nmol/L). The automated method is suitable for therapeutic monitoring of fluvoxamine in the treatment of psychiatric patients.

Adult↗
PubMed1991

Determination of benperidol and its reduced metabolite in human plasma by high-performance liquid chromatography and electrochemical detection.

An isocratic high-performance liquid chromatographic method with electrochemical detection for the quantification of benperidol and its suggested reduced metabolite TVX Q 5402 in human plasma is described. The method included a two-step solid-phase extraction on reversed-phase and cation-exchange material, followed by separation on a cyanopropyl silica gel column (5 microns; 250 mm x 4.6 mm I.D.). The eluent was 0.15 M acetate buffer (pH 4.7) containing 25% acetonitrile (w/w). Spiperone served as internal standard. The inclusion of the cation-exchange step provided sample purity higher than those achieved with other methods. After extraction of 1 ml of plasma, concentrations as low as 0.5 ng/ml were detectable for both benperidol and the metabolite. In plasma samples collected from a schizophrenic patient treated with a single oral dose of 6 mg of benperidol, plasma levels of benperidol and of the metabolite could be measured from 20 min to at least 12 h after administration.

Benperidol↗
PubMed1991

Savoxepine: invalidation of an "atypical" neuroleptic response pattern predicted by animal models in an open clinical trial with schizophrenic patients.

The new tetracyclic compound savoxepine exhibits potent antidopaminergic effects with preferential activity in the hippocampus as compared to striatum in rat brain. As a result of behavioural animal models and regional differences in dopamine receptor binding characteristics, it has been suggested to possess an "atypical" neuroleptic response pattern. In an open clinical trial, savoxepine was administered to 12 in-patients suffering from paranoid schizophrenia and schizophreniform disorder (DSM-III). Eight patients were treated with a stable dose of 0.5 mg per day throughout the study, while in the remaining patients higher doses up to 20 mg/day were administered. Mean total BPRS scores and subscores demonstrated a moderate improvement of mainly positive schizophrenic symptoms. In contrast to animal test results, savoxepine in a broad dose range produced typical untoward extrapyramidal symptoms in the majority of patients. Our results indicate that savoxepine may not possess the expected "atypical" neuroleptic response pattern, and that the predictive validity of the animal models in question used to separate antipsychotic effects from extrapyramidal reactions may be ill-founded.

Adult↗
PubMed1991

[Zotepine versus perazine in patients with paranoid schizophrenia: a double-blind controlled trial of its effectiveness].

The dibenzothiepine zotepine is a new potential "atypical" neuroleptic exhibiting powerful antiserotonergic and antidopaminergic properties. The efficacy of zotepine was evaluated in a double-blind controlled trial versus the tricyclic neuroleptic perazine in 41 patients suffering mainly from the paranoid-hallucinatory type of schizophrenia. The key outcome variable was the extent of mental disturbance as defined by the total score of the BPRS. Additional outcome variables were GAS and CGI. In addition, adverse reactions and extrapyramidal side effects were assessed according to the FSUCL scale and the Gerlach and AIMS rating scale, respectively. Additional variables recorded were blood pressure, heart rate and routine laboratory parameters as well as electrocardiogram and electroencephalogram. In the first two days, standard equivalent doses of both drugs were administered. Thereafter, doses were administered as required. The efficacy of both substances was compared after 7, 14 and 28 days of treatment. Both drugs showed a similar antipsychotic efficacy. Under zotepine treatment a 55% improvement of the BPRS total score was observed while perazine led to a 41% BPRS score reduction. After 7 days the zotepine group was significantly more improved than the perazine group, possibly due to a dosing effect in the perazine group. In the zotepine group, fewer adverse reactions and a better benefit/risk index were observed although the differences between the two treatment groups did not reach levels of statistical significance. There were no drug-specific abnormal laboratory findings. Thus, in the present study there was no significant difference between zotepine and perazine with respect to antipsychotic efficacy and side-effect rates. However, zotepine showed a trend to a better benefit/risk index at the end of treatment.

Adult↗
PubMed1991

Extrapyramidal symptoms and their relationship to clinical efficacy under perphenazine treatment. A controlled prospective handwriting-test study in 22 acutely ill schizophrenic patients.

In order to verify the hypothesis of a strict relationship between clinical improvement and extrapyramidal side-effects, especially micrographia, twenty-two acutely ill schizophrenics were treated with perphenazine in a controlled prospective 28-day trial. During the study period, psychopathometric data, prolactin plasma levels, and handwriting samples were collected. According to the remission criteria fixed before the study began (both BPRS less than or equal to 25 and GAS greater than or equal to 80 points), 45.5% (10/22) of the total patient sample were classified as treatment responders. Handwriting tests were quantified in 21 patients. "Positive" handwriting results, i.e., a reduction of at least 13% in the overall area of 50% or more of the handwriting samples collected during the trial, were demonstrable in three of nine responders (33%) and nine of twelve nonresponders (75%). These results show that there is no positive correlation between clinical response and reduction in handwriting area. Consequently, the handwriting test is unable to predict clinical response. It is only one of a number of parameters with which to monitor the neurological side-effects of neuroleptic treatment. Outcome parameters show that psychopathological remission can be achieved with low neuroleptic dosages and few or virtually no extrapyramidal side-effects.

Acute Disease↗
PubMed1988

Improving depression severity assessment--I. Reliability, internal validity and sensitivity to change of three observer depression scales.

The Hamilton Depression Scale (HAMD) is the most commonly used scale for depression severity assessment and for antidepressant treatment evaluation. Alternative scales have been proposed by Bech and Rafaelsen (BRMS) and by Montgomery and Asberg (MADRS) to try to overcome the shortcomings of HAMD: they are based on different concepts of severity and different scaling procedures. Comparisons with respect to reliability, validity and ability to detect change have been performed using these scales in different samples. The BRMS proved superior. This result makes it necessary to question the usual procedure of testing the efficacy of antidepressants by means of HAMD alone. Problems in defining the severity of depression and in testing the validity of severity scales are discussed.

Adult↗
PubMed1987

Stupor and affective state: alleviation of psychomotor disturbances by lorazepam and recurrence of symptoms after Ro 15-1788.

In a single patient suffering from a major depressive episode with melancholia (DSM-III), both severe psychomotor symptoms, such as stupor and mutism, and mood disturbances could be abolished completely and promptly by administration of the benzodiazepine lorazepam. Remission of symptoms was entirely and immediately reversed by the benzodiazepine antagonist Ro 15-1788. These drug effects were constantly reproducible. Possible mechanisms of action and the influence of GABAergic neurotransmission on affective and psychomotor state are discussed.

Adult↗