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Biomedical subjects

S Kasper

Publications and source records attributed to S Kasper.

At least 73 records · Page 4Linked to original sources
PubMed2001

Quetiapine: efficacy and tolerability in schizophrenia.

Quetiapine, in common with clozapine, has a greater affinity for 5-HT(2) receptors than D(2) receptors and preclinical studies have consistently predicted efficacy against schizophrenia, with a low potential for causing extrapyramidal symptoms (EPS). In clinical trials, the efficacy of quetiapine was consistently superior to placebo and it was effective against both positive and negative symptoms. Quetiapine was also at least as effective as chlorpromazine or haloperidol in improving the symptoms of acute schizophrenia and moreover was associated with higher response rates. The consistent, placebo-level incidence of EPS associated with quetiapine in clinical trials was not seen with haloperidol. Thus, the combination of efficacy comparable to other antipsychotic agents, with an acceptable side effect and tolerability profile, provides support for the use of quetiapine as a first-line antipsychotic agent in the long-term treatment of schizophrenia.

Antipsychotic Agents↗
PubMed2001

Dopamine transporter availability in symptomatic depressed patients with seasonal affective disorder and healthy controls.

BACKGROUND: During recent years hypotheses about the pathophysiology of seasonal affective disorder/winter type (SAD) have focused monoaminergic mechanisms. There is substantial evidence that serotonergic systems play an important role. The potential role of catecholaminergic pathways has not been fully explored. METHODS: Eleven drug-free, symptomatic depressed patients with SAD and 11 healthy age- and gender-matched healthy controls were invited to participate in a 123Ibeta-CIT single photon emission computed tomography (SPECT) study to assess striatal density of dopamine transporters (DATs). The cerebellum was used as reference region. Ratios were calculated between mean counts in left and right striatum and cerebellum. These ratios minus I represent specific/non-displaceable binding and are assumed to be directly related to DAT availability at the time of binding equilibrium. RESULTS: Displaceable 153Ibeta-CIT binding in the area corresponding to the left striatum was significantly reduced in SAD patients compared to healthy controls (10.49+/-0.91 v. 1195+/-1.54, respectively; 2-tailed P = 0.017, Mann-Whitney U test). CONCLUSIONS: These data suggest reductions in the availability of striatal DAT binding sites in untreated symptomatic depressed SAD patients. It remains unclear whether these reductions represent a primary defect or an attempt to overcome a state of possible lowered dopamine availability in the synaptic cleft during a depressive episode of SAD. However, these findings provide evidence that brain dopaminergic systems may be involved in the pathophysiology of SAD.

Adult↗
PubMed2001

Monoaminergic function in the pathogenesis of seasonal affective disorder.

Seasonal affective disorder/winter type (SAD) is characterized by recurrent depressive episodes during autumn and winter alternating with non-depressive episodes during spring and summer. Light therapy with full-spectrum, bright white light has been shown to be effective for this condition. Several hypotheses have been discussed in the literature about the pathogenesis of SAD. The most prominent includes disturbances in central monoaminergic transmission. Evidence can be inferred from studies showing a seasonal rhythm of central and peripheral serotonergic functioning which may be a predisposing factor for SAD. Some of the symptoms of SAD are believed to represent an attempt to overcome a putative deficit in brain serotonergic transmission. Moreover, 5-HT receptor challenge studies suggest altered activity at or downstream to central 5-HT receptors. Monoamine depletion studies support hypotheses about serotonergic and catecholaminergic dysfunctions in SAD and suggest that light therapy may well compensate for this underlying deficit. Further, albeit indirect, support for the importance of monoaminergic mechanisms in SAD and its involvement in the mechanism of the action of light therapy comes from studies showing antidepressant efficacy of serotonergic and noradrenergic antidepressants in the treatment of SAD. Altogether, disturbances in brain monoaminergic transmission seem to play a key role in the pathogenesis of SAD; monoaminergic systems may also play an important role in the mechanisms of the action of light therapy.

Biogenic Monoamines↗
PubMed2001

CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages.

OBJECTIVE: This review aimed to provide distinct dose recommendations for antidepressants based on the genotypes of cytochrome P450 enzymes CYP2D6 and CYP2C19. This approach may be a useful complementation to clinical monitoring and therapeutic drug monitoring. METHOD: Our literature search covered 32 antidepressants marketed in Europe, Canada, and the United States. We evaluated studies which had compared pharmacokinetic parameters of antidepressants among poor, intermediate, extensive and ultrarapid metabolizers. RESULTS: For 14 antidepressants, distinct dose recommendations for extensive, intermediate and poor metabolizers of either CYP2D6 or CYP2C19 were given. For the tricyclic antidepressants, dose reductions around 50% were generally recommended for poor metabolizers of substrates of CYP2D6 or CYP2C19, whereas differences were smaller for the selective serotonin reuptake inhibitors. CONCLUSION: We have provided preliminary average dose suggestions based on the phenotype or genotype. This is a first attempt to apply the new pharmacogenetics to suggest dose-regimens that take the differences in drug metabolic capacity into account.

Antidepressive Agents↗
PubMed2001

Hypericum perforatum--a review of clinical studies.

St. John's wort (Hypericum perforatum) has been used as a medicinal herb for over 2000 years. Over the past 2 decades, its application as a plant extract for treating depression has undergone rigorous scientific investigation, and its effectiveness has been shown in studies comparing it with placebo and preference antidepressants. Safety and tolerability studies have revealed that St. John's wort (SJW) preparations have better safety and tolerability profiles than synthetic antidepressants. The indications for St. John's wort preparations comprise patients with mild or moderate depression. Based on the existing literature, limitations to efficacy in more severe cases as well as interactions and contraindications have to be respected.

Antidepressive Agents↗
PubMed2001

Citalopram 20 mg, 40 mg and 60 mg are all effective and well tolerated compared with placebo in obsessive-compulsive disorder.

Serotonin reuptake inhibitors appear to be uniquely effective treatments for obsessive-compulsive disorder (OCD). This double-blind, placebo-controlled study was the first trial to assess the efficacy of the most selective of the serotonin reuptake inhibitors, citalopram, in OCD. A total of 401 patients were randomized to receive citalopram 20, 40 or 60 mg/day or placebo for 12 weeks. All three doses of citalopram were significantly more effective than placebo measured on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) change score (P < 0.01). The highest response rate, defined as 25% improvement in Y-BOCS entry score, was observed in the 60 mg group (65%). This compared with 52% and 57.4% in the 40 mg and 20 mg groups. Response rate on placebo was 36.6% (P < 0.05 for all three doses of citalopram compared to placebo). There was no significant difference between the individual doses of citalopram. An advantage was seen for citalopram on the Sheehan Disability Scale compared with placebo (P < 0.05 on all three citalopram groups versus placebo for both the work situation and the family life and home responsibilities and P < 0.05 on citalopram 60 mg and 20 mg versus placebo for the social life and home activities). Citalopram was well tolerated; only 4 to 6 patients in each dose group discontinued the study prematurely due to adverse events.

Activities of Daily Living↗
PubMed2001

Zotepine in the treatment of acute hospitalized schizophrenic episodes.

The atypical antipsychotic zotepine was studied in an open, multicentre uncontrolled, post-marketing surveillance study in 108 schizophrenic patients hospitalized in 12 trial centres in Austria. Within the dosage range of 50-450 mg (mean at the end of the study, 207 +/- 125 mg/day), a significant reduction of positive as well as negative symptoms was noted. There was no increase in extrapyramidal side-effects during the study and a significant decrease in akathisia scores. The medication was well tolerated during the 42-day observation period. Zotepine improved both positive and negative symptoms and was not accompanied by extrapyramidal side-effects, justifying its classification as an atypical antipsychotic.

Acute Disease↗
PubMed2001

Risperidone olanzapine drug outcomes studies in schizophrenia (RODOS): efficacy and tolerability results of an international naturalistic study.

The Risperidone Olanzapine Drug Outcomes studies in Schizophrenia (RODOS) programme was an international series of naturalistic studies designed to evaluate drug use patterns and outcomes. RODOS consisted of retrospective chart reviews performed in patients who had been admitted to hospital and treated in 61 centres in nine countries. The analysed population consisted of 1901 patients with diagnoses of schizophrenia or schizoaffective disorder. The mean (SD) daily doses of risperidone and olanzapine were 5.3 (2.6) mg/day and 14.5 (5.1) mg/day, respectively. Patients treated with risperidone stayed an average of 3.8 days less in hospital compared to those receiving olanzapine (time to discharge was 43.6 days versus 47.4 days, respectively; P = 0.004). Risperidone was rated as effective in significantly more patients than olanzapine (84% versus 79%; P = 0.01). The time to onset of efficacy was significantly shorter with risperidone than with olanzapine (P < 0.001). The numbers of adverse events in the two treatment groups were not significantly different (13% risperidone, 11% olanzapine; P = 0.1). Correcting for small but statistically significant baseline differences between the two treatment groups did not produce a substantive change in the magnitude or significance of any outcome parameter. In conclusion, the clinical outcomes reported by RODOS suggest that risperidone may be more effective as a first-line therapy drug for schizophrenia than olanzapine.

Adult↗
PubMed2001

Risperidone olanzapine drug outcomes studies in schizophrenia (RODOS): health economic results of an international naturalistic study.

We report the health economic data from the Risperidone Olanzapine Drug Outcomes studies in Schizophrenia (RODOS) programme. Details of the efficacy and tolerability data from RODOS are available in a companion paper. The population analysed during RODOS consisted of 1901 patients with diagnoses of schizophrenia or schizoaffective disorder. The mean +/- SD daily dose of olanzapine treatment was 14.5 +/- 5.1 mg compared to 5.3 +/- 2.6 mg for risperidone. Use of concomitant neuroleptics (risperidone, 65%; olanzapine, 62%; P = 0.2) and other concomitant drugs (risperidone, 76%; olanzapine, 73%; P = 0.2) was similar in both groups. The mean +/- SD total costs of all inpatient drugs was significantly (P < 0.001) higher for olanzapine (US$ 297.5 +/- 305.1) than risperidone (US$159.9 +/- 183.3). Although this difference in the average total costs in part reflects the longer treatment duration for olanzapine compared to risperidone (34 days versus 31 days), the cost difference remained when looking at costs on a daily basis. The mean +/- SD daily cost of all inpatient drugs was also significantly (P < 0.001) higher for olanzapine (US$7.7 +/- 4.0) than for risperidone (US$ 4.6 +/- 2.9). These findings were very consistent across all nine countries. The results from RODOS suggest that treatment costs are significantly higher with olanzapine than with risperidone without any clinical benefit to offset this.

Adult↗
PubMed2001

Fluoxetine treatment in patients with recurrent brief depression.

Recurrent brief depression (RBD) fulfills DSM-IV criteria for major depression except duration. Depressive episodes last at least 2 days but less than 2 weeks occurring at least once a month for 12 consecutive months without association to the menstrual cycle. RBD has a high prevalence in the general population (approximately 10%). At present, there are few double-blind controlled studies indicating that selective serotonine reuptake inhibitors (SSRIs) might not be effective in treatment of RBD. However, most of those studies include patients with a history of frequent suicide attempts and depressive episodes lasting shorter 2 weeks. It has previously been shown that fluoxetine was effective in patients with RBD in an open-label study. The objective of our study was to reinvestigate these contradictory results concerning the effectiveness of fluoxetine in patients with RBD. Seventeen patients with RBD according to DSM-IV and ICD-10 diagnostic criteria, who had no history of major depression were treated with a dosage of 20-40 mg fluoxetine daily. Patients had to keep a diary in order to document psychopathological symptoms according to DSM-IV. We also used the 21-item Hamilton Depression Rating Scale (HAM-D), the Beck Depression Inventory (BDI) and the Clinical Global Impressions (CGI). Duration of the study was 8 weeks. The diaries of nine patients were observed for a clinical observation period of 20 weeks after the end of the study with continued fluoxetine treatment. Two patients who initially fulfilled diagnostic criteria for RBD suffered from depressive episodes that lasted longer than 2 weeks. Therefore, their data had to be excluded from primary analysis. In the remaining 15 patients, we showed statistically significant improvement of depressive episodes measured by patient's diary, HIAM-D, BDI and CGI that persisted over the clinical observation period. Frequency of depressive episodes showed a significant decrease during fluoxetine treatment. Duration and severity of the single depressive episodes also decreased but did not reach statistical significance. In accordance with previous studies, fluoxetine could be a treatment option for patients with RBD. Treatment of RBD with SSRIs has been discussed controversially in the literature. Our study shows the effectiveness of fluoxetine in this depressive disorder. To confirm these preliminary results, a double-blind controlled study is necessary.

Adult↗
PubMed2001

A 28-week, double-blind, placebo-controlled study with Cerebrolysin in patients with mild to moderate Alzheimer's disease.

Cerebrolysin (Cere) is a compound with neurotrophic activity which has been shown to be effective in the treatment of Alzheimer's disease (AD) in earlier trials. The efficacy and safety of repeated treatments with Cere were investigated in this randomized, double-blind, placebo-controlled, parallel-group study. One hundred and forty-nine patients were enrolled (76 Cere; 73 placebo). Patients received i.v. infusions of 30 ml Cere or placebo 5 days per week for 4 weeks. This treatment was repeated after a 2-month therapy-free interval. Effects on cognition and clinical global impressions were evaluated 4, 12, 16, and 28 weeks after the beginning of the infusions using the Clinical Global Impression (CGI) and the Alzheimer's Disease Assessment Scale-cognitive subpart (ADAS-cog). All assessments, including the 28-week follow-up visit were performed under double-blind conditions. At week 16, the responder rate of the Cere group was 63.5% on the CGI, compared to 41.4% in the placebo group (P < 0.004). In the ADAS-cog, an efficacy difference of 3.2 points in favour of Cere was observed (P < 0.0001). Notably, improvements were largely maintained in the Cere group until week 28, 3 months after the end of treatment. Adverse events were recorded in 43% of Cere and 38% of placebo patients. Cere treatment was well tolerated and led to significant improvement in cognition and global clinical impression. A sustained benefit was still evident 3 months after drug withdrawal.

Aged↗
PubMed2001

Topiramate as a mood stabilizer.

Topiramate is a novel anticonvulsant agent with a broad spectrum mechanism of action, and recent clinical reports indicate that it may have mood stabilizing properties in bipolar disorder. Therefore, we treated a 41-year-old woman who had 12 previous hospitalizations for acute mania during a 10-year history of bipolar I disorder with this compound. Since 1991, the patient had been treated with carbamazepine, valproate and lamotrigine with limited success. At the beginning of a new manic episode, topiramate was started in the outpatient clinic. Eight weeks after initiation of treatment, the patient was hospitalized. This inpatient treatment lasted less than 3 weeks. Subsequently, the patient has not been hospitalized again. Topiramate was well tolerated. Even though, during subsequent topiramate treatment, a serious life event (suicide attempt of brother) induced re-occurence of the patient's psychopathology, which did not require hospitalization. Fortunately, inpatient treatment was not necessary due to an increase of topiramate dosage and addition of risperidone and clonazepam. The patient, now on 200 mg/day, is mostly asymptomatic and has functioned well for over 17 months, in contrast to 13 hospitalizations during the previous 10 years.

Acute Disease↗
PubMed2001

Predictors of response to pharmacotherapy with citalopram in obsessive-compulsive disorder.

Although serotonin reuptake inhibitors (SRIs) are the medications of choice in the treatment of obsessive-compulsive disorder (OCD), only 50-60% of patients respond to a single trial of any of these agents. Improved knowledge of the predictors of response to treatment may have important clinical implications. Data from a large randomized placebo-controlled trial of citalopram in OCD was analysed using logistic regression to determine predictors of response. Demographic (age, sex), clinical (OCD severity and duration, depression severity, prior treatment) and trial variables (citalopram dose, treatment duration) were included. Subjects with longer duration of OCD, more severe OCD symptoms or previous selective SRI use were less likely to be responders in the citalopram trial. In contrast, subjects who received adequate medication doses for sufficient periods of time in the citalopram trial were more likely to be responders. Despite greater awareness of OCD in recent years, there is evidence that the disorder continues to be underdiagnosed and undertreated. The data here emphasize the crucial importance of early diagnosis and treatment of OCD, and of pharmacotherapy with appropriate dose and duration.

Adolescent↗
PubMed2001

Inverse relation between stimulus intensity and seizure duration: implications for ECT procedure.

A retrospective analysis of the effects of electroconvulsive therapy (ECT) was performed for two groups of 11 patients matched according to age (mean age, 52 years), sex, and diagnosis. Group 1 received ECT according to the age-dose protocol; group 2 was treated according to the titration method. A higher dose relative to the seizure threshold appeared to shorten the seizure duration. At the first treatment, the correlation between stimulus intensity and seizure duration was negative. In the titration group, the initial mean charge of 91 mC resulted in a seizure duration of 51 s, whereas in the age-dose group the seizure duration of 31 s was significantly shorter despite a higher mean charge of 312 mC. Seizure duration decreased during the ECT course in the group treated first at low dose (titrated) and then at 2.5 times the initial threshold. High stimulus intensity represented adequate treatment, although it produced short seizures. Thus, seizure duration proved to be an unreliable guideline for effective treatment. Furthermore, focus on seizure duration led to frequent high-dose restimulation in the elderly. The titration method obviates inadequate or excessive charges because the seizure threshold must first be determined.

Adult↗
PubMed2001

Study of family history in seasonal affective disorder.

OBJECTIVE: In our investigation we assessed the risk of morbidity for psychiatric disorders among the first-degree relatives of patients with seasonal affective disorders (SAD) and compared it with a control group of patients suffering from nonseasonal mood disorders (NSMD). METHODS: Over a period of 12 months (June 1994 to May 1995) we recruited patients consecutively admitted to our psychiatric university outpatient clinic in a prospective study. All patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, revised 4th edition. A total of 344 patients presented themselves with a diagnosis of affective disorder. Out of these, 36 were diagnosed as having SAD. From the same group of 344 patients, we selected a matched control group of 36 patients suffering from NSMD. The experimental and control groups were matched according to sex, age, severity of illness and number of siblings. RESULTS: There was no significant difference concerning the lifetime prevalences for psychiatric disorders among the fist-degree relatives in both groups (SAD = 16.5% and NSMD = 19%). CONCLUSION: It seems that there is no difference in familiarity for psychiatric disorders between SAD and NSMD.

Adult↗
PubMed2001

Inverse relationship between serotonin 5-HT(1A) receptor binding and anxiety: a [(11)C]WAY-100635 PET investigation in healthy volunteers.

OBJECTIVE: The authors investigated the relationship between anxiety--a facet of the Revised NEO Personality Inventory dimension of neuroticism--and serotonin 5-HT(1A) receptor binding potential. METHOD: Positron emission tomography with [(11)C]WAY-100635 was used to estimate regional 5-HT(1A) binding potential in 19 healthy volunteers who completed the Revised NEO Personality Inventory. Correlation coefficients were calculated to determine the degree of association between 5-HT(1A) binding potential and personality inventory measures. RESULTS: There was a significant negative correlation between 5-HT(1A) binding potential and anxiety in four regions: the dorsolateral prefrontal cortex, anterior cingulate cortex, parietal cortex, and occipital cortex. CONCLUSIONS: The inverse relationship between 5-HT(1A) receptor binding potential and anxiety is consistent with 1) animal models that have shown higher anxiety in mice lacking 5-HT(1A) receptors and 2) clinical trial data that have demonstrated antianxiety properties of partial 5-HT(1A) agonists.

Adult↗
PubMed2001

Gene duplication gives rise to a new 17-kilodalton lipocalin that shows epididymal region-specific expression and testicular factor(s) regulation.

Using transgenic mice, we have recently shown that 5 kb of the 5'-flanking region of the mouse epididymal retinoic acid-binding protein (mE-RABP) gene contains all of the information required for spatial and temporal gene expression in the epididymis. To identify the important cis-DNA regulatory element(s) involved in the tissue-, region-, and cell-specific expression of the mE-RABP gene, the 5-kb DNA fragment was sequenced. A computer analysis of the nucleotide sequence showed the presence of a new gene located 1.7 kb upstream from the mE-RABP gene transcription initiation site. The analysis of the open reading frame showed that the new gene encoded a putative 17-kDa lipocalin (named mEP17) related to mE-RABP. A 600-bp complementary DNA encoding mEP17 was cloned by rapid amplification of 3'-cDNA ends from epididymal total RNA. Two mEP17 RNA species (1 and 3.1 kb in size) were detected by Northern blot in the epididymis, but not in other tissues tested. In situ hybridization analyses showed that, unlike mE-RABP messenger RNA (mRNA), which is expressed in the distal caput epididymidis, mEP17 mRNA was detected only in the principal cells of the initial segment. The spatial expression and homology with mE-RABP suggest that mEP17 may act as a retinoid carrier protein within the epididymis. mEP17 mRNA expression disappeared 5 days postcastration. Four days after unilateral castration, mEP17 mRNA had nearly disappeared in the epididymis from the castrated side, but not from the intact side. In addition, testosterone replacement to bilaterally castrated mice failed to restore gene expression. We conclude that mEP17 gene expression is dependent on testicular factors circulating in the luminal fluid. Together our results suggest that mE-RABP and mEP17 genes were generated by duplication and that evolution led to a different region-specific gene expression and regulation in the epididymis.

Amino Acid Sequence↗