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Biomedical subjects

S Kasper

Publications and source records attributed to S Kasper.

At least 217 records · Page 12Linked to original sources
PubMed1995

[EEG changes in schizophrenic diseases--a critical review].

To identify specific changes in the electroencephalogram of schizophrenic patients has been an important target of clinical neurophysiology ever since the introduction of the EEG. Results of EEG-amplitude- and frequency-analysis in schizophrenics--although sometimes contradictory--are presented. Special emphasis is laid upon possible clinical applicabilities, for instance the prediction of the clinical course by means of neurophysiological changes after administration of a neuroleptic test dose. Finally, the usefulness of examining electrophysiological changes in such a heterogeneous group, as schizophrenics are, is discussed critically.

Antipsychotic Agents↗
PubMed1995

Antidepressant efficacy in relation to item analysis and severity of depression: a placebo-controlled trial of fluvoxamine versus imipramine.

In this investigation, the antidepressant efficacy of fluvoxamine and imipramine was compared in a randomized, double-blind, placebo-controlled study lasting 4 weeks; 338 depressed patients were recruited at five North American centres. For the efficacy analyses an intent-to-treat sample was defined. The global efficacy of the two drugs was assessed by the Hamilton Depression scale (HAM-D) and Clinical Global Impression (CGI) scores. Antidepressant activity was also assessed using the percentage of responders on the CGI "improvement" scale. In addition the time of onset of antidepressant effect was evaluated by weekly analysis of individual HAM-D items. The intent-to-treat sample was stratified retrospectively according to the severity of the depression (mild, moderate or severe). Regarding global efficacy, compared with placebo, only fluvoxamine significantly improved the HAM-D total scores at Week 4 (p < 0.05). There was a suggestion from individual HAM-D item scores (depressed mood, suicide, psychic anxiety) that fluvoxamine had an earlier effect than imipramine. Overall, compared with placebo, more HAM-D items were improved by fluvoxamine than imipramine. Fluvoxamine but not imipramine was significantly superior to placebo in severely depressed patients as shown by improvements in the HAM-D score (p < 0.01) and the CGI "improvement" score (p < 0.05). Side effect profiles for the active agents were typical for their pharmacological category:imipramine was associated with anticholinergic effects, particularly dry mouth, and fluvoxamine was associated with nausea and vomiting.

Adult↗
PubMed1995

Comparison of compliance between serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis.

A meta-analysis of 67 published randomized controlled clinical trials comparing selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), which measured discontinuation rates for side effects and lack of efficacy, was performed. All multiple publications and trials using non-TCA comparators were excluded. Ten studies were placebo controlled; these were analysed separately. Overall, the difference in withdrawals due to side effects of SSRIs and TCAs was -4.5% (p = 0.0004) and that due to lack of efficacy was 0.1% (p = 0.86). In the placebo-controlled trials the differences between the two groups were -7.9% and -0.1% (p = 0.06 and 0.96), respectively. These results demonstrate that SSRIs have a significant and clinically important advantage over TCAs with respect to tolerability, whereas efficacy is similar. Treatment failure due to poor compliance can increase health-care costs: therefore, in selecting an antidepressant for the first-line treatment of major depressive disorders, the risks, benefits and costs of each type of treatment need to be critically evaluated.

Antidepressive Agents, Tricyclic↗
PubMed1995

Clinical efficacy of mirtazapine: a review of meta-analyses of pooled data.

Mirtazapine is a novel antidepressant with a unique mode of action, which can be best summarized as a noradrenaline and specific serotonin antidepressant. Its unique mode of action, involving both the noradrenergic and serotonergic neurotransmitter systems, results in strong clinical efficacy. A comprehensive clinical trial programme in Europe and the United States has demonstrated that mirtazapine has clear clinical benefits in a broad range of patients treated across different therapeutic settings. The individual placebo-controlled trials and a meta-analysis on pooled efficacy data from all available placebo-controlled studies have shown that mirtazapine has sustained antidepressant efficacy, as assessed by changes from baseline in group mean scores on the Hamilton Rating Scale for Depression (HAMD) and in the depressed mood item, from week 1 throughout the whole study period. Corroborative evidence on the clinical efficacy of mirtazapine has been obtained in comparative studies with antidepressant drugs of well established efficacy, such as amitriptyline, clomipramine, doxepin and trazodone. As with the placebo-controlled studies, a meta-analysis was performed on data from all the randomized, double-blind, comparative studies of mirtazapine and amitriptyline. Data from 732 patients were available (364 patients taking mirtazapine and 368 taking amitriptyline) for efficacy analysis. Equivalent improvements in total 17-item HAMD scores from baseline were observed in both treatment groups at all scheduled assessments and at the end of the study period, and similarly high percentages of patients responded to treatment with either mirtazapine (70%) or amitriptyline (73%). The efficacy of mirtazapine was also assessed in the treatment of moderately (baseline 17-item HAMD score 18-24) or severely depressed patients (baseline 17-item HAMD score > or = 25). A meta-analysis was performed on the pooled data from the moderately or severely depressed patients in the comparative studies of mirtazapine and placebo or mirtazapine and amitriptyline. Statistically and clinically significant improvements from baseline were seen in both moderately and severely depressed patients treated with mirtazapine compared with placebo, while an equivalent extent of improvement was present with mirtazapine and amitriptyline. A similar pattern was observed in the improvement of depressed mood (HAMD item 1) and other clinically important symptoms of depression: mirtazapine was significantly more efficacious than placebo, and of equivalent efficacy to amitriptyline. Therefore, it can be concluded that the new antidepressant mirtazapine offers distinct therapeutic benefits for a variety of depressed patients in either in- or outpatient settings.

Antidepressive Agents, Tricyclic↗
PubMed1995

[Psychiatrically relevant side effects of non-psychopharmacological pharmacotherapy].

We briefly review the possibilities of side effects caused by therapy with drugs other than psychotropic agents. These complications are mainly depressive/manic, paranoid-hallucinatoric/deliriant or anxiety/panic syndromes. Especially elderly patients and patients with multiple diseases are the preferred group with these side effects, because they are most likely to show a disturbance of blood-brain barrier and renal clearance. We will discuss the psychiatrically meaningful side effects of frequently used drugs, and we will present a concept of how to reduce such unwanted side effects.

Aged↗
PubMed1995

Mice doubly deficient in the genes for P0 and myelin basic protein show that both proteins contribute to the formation of the major dense line in peripheral nerve myelin.

In search for the molecular mechanisms underlying the formation of the major dense line in peripheral nerve myelin we investigated mice deficient in the myelin proteins P0 and MBP. In mice lacking both molecules axons were enwrapped by myelin-like processes devoid of the major dense line, while mice deficient in either protein showed, respectively, partial and normal compaction. Mice heterozygous for P0 but devoid of MBP showed myelin of reduced thickness around axons of normal caliber. Both molecules thus contribute to the formation of the major dense line and to the determination of myelin thickness. Furthermore, our observations modify the view that axon caliber is dependent on normal myelin.

Animals↗
PubMed1995

Bioequivalence and absolute bioavailability of oblong and coated levomepromazine tablets in CYP2D6 phenotyped subjects.

The bioequivalence and absolute bioavailability of oblong and coated levomepromazine tablets were studied in 12 healthy volunteers. A 1-hour intravenous infusion served as the reference. Serum concentrations of levomepromazine were quantified with a specific high-performance liquid chromatographic method and electrochemical detection. The 2 oral formulations were bioequivalent. After oral administration of oblong and coated levomepromazine tablets the mean serum concentration versus time profiles were similar and the pharmacokinetic parameters showed wide interindividual variations. There was a 21% absolute bioavailability of levomepromazine, indicating a pronounced presystemic metabolism. The total serum clearance and the apparent volume of distribution at steady state were 48 +/- 14 l/min and 980 +/- 213 l, respectively. These pharmacokinetic parameters were also investigated with respect to the CYP2D6 polymorphism, i.e. via dextromethorphan phenotyping of 9 subjects, 3 subjects were poor metabolizers, and 6 extensive metabolizers. The Spearman's rank-ordered correlation analysis did not reveal a significant correlation between the pharmacokinetic parameters AUC, Cmax and t1/2 after oral administration of oblong and coated levomepromazine tablets and the metabolic ratios of dextromethorphan, suggesting that levomepromazine is not metabolized to any major extent by the isoenzyme CYP2D6.

Administration, Oral↗
PubMed1994

Cooperative binding of androgen receptors to two DNA sequences is required for androgen induction of the probasin gene.

The functional and structural interactions of two androgen receptor-binding sites in the 5'-flanking DNA of the rat probasin gene were determined. Deletion mapping and DNase I footprinting analysis had previously identified two androgen receptor-binding sites (ARBS) necessary for androgen induction of the probasin gene: ARBS-1, which resembled a glucocorticoid-responsive element, and ARBS-2, which had a unique sequence. In this study, maximal androgen induction in transient transfection studies only occurred when both sites were present. Neither binding site functioned independently, and deletion of the DNA sequence between the sites resulted in a 60% loss of androgen inducibility. Moreover, point mutations in either ARBS-1 or ARBS-2 led to > 90% loss in activity. Scatchard analysis indicated that ARBS-1 and ARBS-2 bound a synthetic androgen receptor, AR2, with Kd values of 20.0 and 6.7 nM, respectively. Consistent with the higher affinity, ARBS-2 bound AR2 at half the threshold concentration (200 ng) of that required in reciprocal DNase I footprinting experiments with ARBS-1. By comparison, protection occurred at a much lower threshold concentration of AR2 (60 ng) and to the same extent over each site when both sites were present, suggesting a cooperative interaction between the two sites. The cooperative effect was further substantiated when a point mutation in ARBS-1 blocked AR2 binding not only to ARBS-1, but also to ARBS-2. Similarly, a point mutation in ARBS-2 also prevented receptor binding to both sites. Androgen-specific regulation of probasin gene transcription therefore required an androgen-responsive region (positions -286 and +28) containing two androgen receptor-binding sites, where the binding of the androgen receptor to both sites occurred in a cooperative, mutually dependent manner.

Androgen-Binding Protein↗
PubMed1994

Evidence for a seasonal form of recurrent brief depression (RBD-seasonal).

We have established a relationship between recurrent brief depression (RBD) and seasonal affective disorder (SAD) in a cohort of 42 outpatients who presented themselves at a clinic for seasonal affective disorder at the Psychiatry Department of the University of Bonn, Germany. Our preliminary data indicate that 31% of the patients who were diagnosed as suffering from either SAD or its subsyndromal form (S-SAD) can also be categorized as RBD (RBD-seasonal) for a 1-year observation period. During the time span of 1 year, RBD-seasonal patients had a mean number of 20 +/- 9 episodes, which were accentuated in fall/winter, outnumbering the ones in spring/summer significantly (P < 0.001). The mean duration of each episode was 4.6 +/- 2.6 days in the RBD-seasonal group. RBD-seasonal patients experienced seasonal changes as more of a problem and reported a lower percentage of first-degree relatives with a history of depression than the non-RBD-seasonal group.

Adult↗
PubMed1994

Clinical response to sleep deprivation and auditory-evoked potentials--preliminary results.

The biological substrate of the antidepressant effect of total sleep deprivation (TSD) has not yet been elucidated. Furthermore, electrophysiological predictors for the response to TSD have not been studied extensively. The aim of present study was to examine the changes in acoustically evoked potentials (N1, P2, N2, P300) after a night of sleep deprivation and to analyze differences between responders and nonresponders. 17 depressive inpatients were studied. The most prominent changes in auditory evoked potentials (responders and nonresponders) were found for the amplitude of the P300 component. Differences between responders and nonresponders could be established for the amplitude and latencies in the N1 component. Responders showed smaller N1 amplitudes before TSD but a higher increase after TSD than nonresponders.

Adult↗
PubMed1994

Efficacy of new generation antidepressants: meta-analysis of imipramine-controlled studies.

When assessing the efficacy of a new antidepressant in comparison with a standard treatment, most clinical trials have come to the conclusion that the nullhypothesis (equal efficacy) cannot be rejected, and have not been reformulated with respect to (at least) equivalent studies. However, it cannot be concluded from this that the compared treatments have the same (or similar) efficacy, because in many of the studies the statistical power is not sufficient. Using the effect-size formula described by Glass et al. (1981), a meta-analysis were performed combining the results of comparative trials of maprotiline, mianserin, viloxazine, trazodone, nomifensine, fluvoxamine, and fluoxetine, performed according to similar objectives and designs (similar patient selection, double-blind, randomized, etc.) and with imipramine as reference compound. Together with the results of a former meta-analysis of amitriptyline-controlled studies (Möller and Haug, 1988) the present investigation indicates differences in efficacy, which in the case of most of the new generation antidepressants is similar to the reference compounds imipramine and amitriptyline.

Adolescent↗
PubMed1994

Hypericum in the treatment of seasonal affective disorders.

Seasonal affective disorder (SAD) represents a subgroup of major depression with a regular occurrence of symptoms in autumn/winter and full remission in spring/summer. Light therapy (LT) has become the standard treatment of this type of depression. Apart from this, pharmacotherapy with antidepressants also seems to provide an improvement of SAD symptoms. The aim of this controlled, single-blind study was to evaluate if hypericum, a plant extract, could be beneficial in treating SAD patients and whether the combination with LT would be additionally advantageous. Patients who fulfilled DSM-III-R criteria for major depression with seasonal pattern were randomized in a 4-week treatment study with 900 mg of hypericum per day combined with either bright (3000 lux, n = 10) or dim (< 300 lux, n = 10) light condition. Light therapy was applied for 2 hours daily. We found a significant (MANOVA, P < .001) reduction of the Hamilton Depression Scale score in both groups but no significant difference between the two groups. Our data suggest that pharmacologic treatment with hypericum may be an efficient therapy in patients with seasonal affective disorder.

Adult↗
PubMed1994

[Fall/winter depression and its therapy].

Seasonal changes in human behavior have been recognized since ancient times. Starting in 1980 systematic research has been carried out by Rosenthal et al. (1984), who described and characterized a psychopathological and clinical syndrome which is linked to fall/winter and shows remission in spring/summer and which was termed seasonal affective disorder (SAD). The symptomatology includes depressed mood, decreased energy, hypersomnia, increased appetite and subsequently weight gain and frequently carbohydrate craving. The efficacy of light therapy with bright, fluorescent, full-spectrum light has been widely demonstrated for treatment of fall/winter SAD. In addition, treatment with selective serotonin reuptake inhibitors appears to be successful in this condition.

Antidepressive Agents↗
PubMed1994

[Electroconvulsive therapy in comorbidity of treatment refractory paranoid hallucinatory psychoses with Parkinson disease].

We report the case of a 49-year-old woman with a therapy resistant paranoid hallucinatory psychosis and coexisting severe symptoms of Parkinson's disease. Over a 3-week period she received electroconvulsive therapy (ECT) 10 times, while the medication of haloperidol 8 mg/day, thioridazin 90 mg/day, metixen 17.5 mg/day and biperiden 6 mg/day was continued. There was a general improvement of the clinical picture, more pronounced for the parkinson symptomatology than for the psychotic disorder.

Antiparkinson Agents↗