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Biomedical subjects

B Küfferle

Publications and source records attributed to B Küfferle.

At least 19 recordsLinked to original sources
PubMed2000

Remission of severe tardive dyskinesia in a schizophrenic patient treated with the atypical antipsychotic substance quetiapine.

In a single inpatient case study, a schizophrenic patient with tardive dyskinesia after prolonged treatment with typical neuroleptics was treated with the new atypical neuroleptic quetiapine, a dibenzothiazepin-derivative. Within 2 weeks of treatment with quetiapine, symptoms of tardive dyskinesia improved; 10 weeks after starting treatment tardive dyskinesia stopped completely. Over the same period, dopamine D2 receptor occupancy decreased substantially, as measured by IBZM-SPECT after 14 and 77 days of treatment.

Adult↗
PubMed2000

Efficacy, cardiac safety and tolerability of sertindole: a drug surveillance.

Sertindole is a novel atypical antipsychotic, which has shown efficacy in the treatment of positive and negative symptoms of schizophrenia in phase II and III studies. Furthermore, these studies have demonstrated tolerability and a favourable side-effect profile. In contrast to classical antipsychotics, sertindole was not associated with extrapyramidal symptoms (EPS). We report drug surveillance data in 34 comorbid and comedicated sertindole treated patients suffering from different psychotic disorders. The drug surveillance consisted of two distinct phases: inpatient treatment and outpatient follow-up. Clinical global impression (severity and improvement of illness), psychotic symptoms, side-effects, and blood parameters have been carefully documented. With special respect to cardiac safety electrocardiograms (ECGs) have been recorded twice (during sertindole treatment and during treatment with an antipsychotic different from sertindole). Recommended ECG-parameters for assessment of the proarrhythmic risk of a drug have been calculated (QTc-, QTc2-interval; QT-, QTc-dispersion). The majority of patients (n = 29) have been treated previously with several typical and/or atypical antipsychotics. We observed a clinical response to sertindole treatment in 29 patients (85%). Both positive and negative symptoms improved with sertindole and no severe side-effects have been documented. EPS occurred at placebo level. A mean QTc-interval prolongation of 19.7 ms (4.7%) has been detected. None of the patients developed clinical or electrocardiographic evidence of cardiac dysrhythmia during sertindole treatment, or other clinical evidence of cardiac abnormalities. In summary, sertindole did show efficacy for positive and negative symptoms together with a favourable side-effect profile. No evidence for an increased proarrhythmic risk has been found.

Adult↗
PubMed2000

Occurrence of mirtazapine-induced delirium in organic brain disorder.

Mirtazapine is the first of a new class of antidepressants, the noradrenergic and specific serotonergic antidepressants. Its antidepressant effect appears to be related to its dual enhancement of both noradrenergic neurotransmission and serotonin 5-HT1 receptor-mediated serotonergic neurotransmission. Mirtazapine has demonstrated superior tolerability to the tricyclic antidepressants, primarily on account of its relative absence of anticholinergic, adrenergic and serotonin-related adverse effects. We observed mirtazapine-induced delirium in one organically depressed and two major depressed patients with subclinical brain disease. The appearance of hallucinations, psychomotoric agitation and cognitive changes after initiation of mirtazapine, and their prompt improvement after drug discontinuation, led to the impression that these were drug-induced phenomena. One possible hypothesis for the observed deliria is a central increase of norepinephrine after acute administration of mirtazapine. Subclinical brain disease might have favoured the occurrence of delirium in the three cases.

Aged↗
PubMed1999

Dopamine- and serotonin-receptors in schizophrenia: results of imaging-studies and implications for pharmacotherapy in schizophrenia.

Considerable progress has been achieved over the past 15 years in uncovering the biological basis of major psychiatric disorders. Since psychopharmacological treatment is thought to act on the underlying biological basis of the disease, brain imaging techniques enable us to understand the mechanism of action of such compounds. Positron emission tomography (PET) as well as single photon emission computerized tomography (SPECT) are important tools used to determine patterns of brain dysfunction and to uncover the mechanism of action for antipsychotic compounds. These techniques allow us to determine striatal D2 receptor as well as cortical 5-HT2A receptor occupancy rates which are linked, at least partly, to clinical efficacy as well as side effect rates. In general it has been shown that atypical antipsychotics have a lower striatal D2 receptor occupancy rate than typical antipsychotics, parallelling the more favorable extrapyramidal side effects of atypical antipsychotics, and as a group effect they have a high 5-HT2A occupancy compared to low rates for typical agents. However, there is no association between striatal D2 receptor occupancy rates and antipsychotic efficacy but 5-HT2A occupancy rates are associated with favorable treatment for depressive symptoms within schizophrenia and improvement of cognitive function. The availability of ligands for measurement of extrastriatal D2 receptors or different 5-HT receptors (e.g. 5-HT1A) will further shed light on the pathophysiology of schizophrenia as well as possible psychopharmacological treatment perspectives.

Antipsychotic Agents↗
PubMed1999

In vivo 123I IBZM SPECT imaging of striatal dopamine-2 receptor occupancy in schizophrenic patients treated with olanzapine in comparison to clozapine and haloperidol.

We investigated the degree of striatal dopamine-2 (D2) receptor occupancy in six schizophrenic patients receiving clinically effective antipsychotic treatment with olanzapine 10-25 mg/day in comparison to patients treated with clozapine 300-600 mg/day (n = 6) or haloperidol 5-20 mg/day (n = 10). 123I Iodobenzamide (IBZM) and single photon emission computerized tomography (SPECT) were used for the visualization of striatal D2 receptors. For the quantification of striatal D2 receptor occupancy, striatal IBZM binding in patients treated with antipsychotics was compared to that in untreated healthy controls (n = 8) reported earlier. Olanzapine led to a mean striatal D2 receptor occupancy rate of 75% (range 63-85). Haloperidol-treated patients showed dose-dependently (Pearson r = 0.64; P < 0.05) a significantly higher (P < 0.05) mean occupancy rate of 84% (range 67-94). During clozapine treatment, the mean D2 receptor occupancy of 33% (range < 20-49) was significantly lower than with olanzapine (P < 0.005). The higher striatal D2 receptor occupancy of haloperidol was correlated with the incidence and severity of extrapyramidal motor side-effects (EPS). No clinical relevant EPS occurred during treatment with olanzapine or clozapine. There was no correlation between the degree of striatal D2 receptor occupancy and clinical improvement.

Adult↗
PubMed1998

Sertindole and dopamine D2 receptor occupancy in comparison to risperidone, clozapine and haloperidol - a 123I-IBZM SPECT study.

The striatal D2 dopamine binding was studied in schizophrenic patients treated with the novel atypical antipsychotic drug sertindole (n=10). Comparisons were obtained with haloperidol (n=8), clozapine (n=6), risperidone (n=11) and untreated healthy controls (n=8) of a dataset which has partly been reported previously. 123I-Iodobenzamide (IBZM) single photon emission computerized tomography (SPECT) was used for estimation of striatal dopamine D2 receptor binding. Sertindole-treated patients exhibited significantly (P < 0.001) lower levels of striatal D2 binding (BG/FC ratio:1.28) compared with those treated with haloperidol (BG/FC ratio:1.09) and risperidone (8 mg:1.18) but significantly (P < 0.005) higher levels compared with clozapine (BG/FC ratio: 1.49). However, if patients were pretreated with a depot neuroleptic, significantly (P < 0.05) higher striatal D2 binding (BG/FC ratio:1.12) has been obtained. Since sertindole has been shown to exert distinct clinical efficacy for treatment of positive and negative symptoms, our data are indicative that antipsychotic efficacy is not associated with a high degree of striatal D2 receptor occupancy in schizophrenic patients.

Adult↗
PubMed1998

Weak antidepressant response after buspirone augmentation of serotonin reuptake inhibitors in refractory severe depression.

Since 1990 open clinical studies and case descriptions reported full or partial antidepressant response after the addition of buspirone to various ongoing antidepressive treatments. Buspirone acts as a partial serotonin agonist at the 5-HT1A receptor. We tried to augment the effect of serotonin-selective re-uptake inhibitors (SSRI) with 30 mg buspirone in a series of 10 in-patients suffering from refractory depression. We observed two cases of partial remission and five other cases with minimal improvement but no case with complete recovery following buspirone augmentation. On the basis of our naturalistic drug surveillance in 10 refractory depressives, we cannot recommend 30 mg-buspirone augmentation of SSRI treatment in severely ill depressives.

Adult↗
PubMed1998

Occurrence of trazodone-induced delirium.

Trazodone, a triazolepyridine derivate, is both chemically and pharmacologically distinct from other serotonin reuptake inhibitors and possesses antidepressant, anxiolytic and hypnotic activity. We observed trazodone-induced delirium in three depressed patients who also suffered from preexisting organic cerebral lesions (two cases) or thyroideal dysfunction (one case). The appearance of hallucinations, psychomotoric agitation, and cognitive changes after initiation of trazodone therapy and their prompt cessation after drug discontinuation led to the impression that these were drug-induced phenomena. One possible hypothesis for the observed deliria is an oversensitivity to the effect of meta-chlorphenylpiperazine, which is a metabolite of trazodone with specific 5-HT agonistic properties.

Adult↗
PubMed1997

Previous treatment as a confounding variable in studies with novel antipsychotics: two cases of high dopamine-2 receptor occupancy with quetiapine.

Previous treatment can be a confounding variable in studies with novel antipsychotics. Quetiapine is a new antipsychotic substance with a low affinity for dopamine-2 (D2) receptors. Preliminary SPECT and PET investigations revealed only a low striatal D2 receptor occupancy rate. However, we present two cases of high striatal D2 receptor occupancy (51% and 71%) measured with 123I IBZM SPECT during quetiapine monotherapy. Both patients had previously received continuous treatment with typical neuroleptics. We present evidence that the previous antipsychotic therapy influenced D2 receptor binding of 123I IBZM during quetiapine treatment weeks after cessation of typical neuroleptics. This might be of importance for the design of clinical trials and brain imaging studies in the future.

Adult↗
PubMed1997

IBZM SPECT imaging of striatal dopamine-2 receptors in psychotic patients treated with the novel antipsychotic substance quetiapine in comparison to clozapine and haloperidol.

We investigated the striatal dopamine-2 (D2) receptor occupancy caused by different antipsychotic substances in 18 psychotic patients (16 with schizophrenic and two with schizoaffective disorder according to DSM-IV) with single photon emission computed tomography (SPECT) using 123I-iodobenzamide (IBZM) as tracer substance. Four patients were treated with the novel antipsychotic compound quetiapine (300-700 mg/day), six with clozapine (300-600 mg/ day) and eight with haloperidol (10-20 mg/day). They were compared with eight healthy controls. Measurement of S/F ratios and consecutive calculation of D2 receptor occupancy revealed a significantly lower striatal D2 occupancy rate with quetiapine and clozapine in comparison to haloperidol. In correspondence with the low striatal D2 receptor occupancy rates and again in contrast to the haloperidol treatment group, there were no extrapyramidal motor side-effects (EPS) in the quetiapine and clozapine treatment groups. Therefore, the reported data support the position that quetiapine can be considered to be an atypical antipsychotic substance due to its relatively weak striatal D2 receptor blocking property and therefore its low propensity to induce EPS.

Adult↗
PubMed1996

Striatal dopamine-2 receptor occupancy in psychotic patients treated with risperidone.

Seventeen psychiatric patients (11 with schizophrenia, 5 with other psychotic disorders, and 1 with obsessive-compulsive disorder) were examined by single photon emission computed tomography with 123I-iodobenzamide (IBZM) as tracer. Patients were treated with risperidone in two different dosage groups (3 mg and 8 mg) and haloperidol (10-20 mg) and compared with eight healthy control subjects. There was a statistically significant difference in basal ganglia/frontal cortex ratios of IBZM binding between controls and all treatment groups. A statistically significant difference was also found concerning these ratios and percentage of dopamine D2 receptor occupancy rates between the treatment groups with lowest ratios and highest percentage of D2 receptor occupancy in the group of patients treated with haloperidol, followed by the group treated with 8 mg of risperidone and the group treated with 3 mg of risperidone.

Adolescent↗
PubMed1994

Clinical, EEG mapping and psychometric studies in negative schizophrenia: comparative trials with amisulpride and fluphenazine.

Based on recent quantitative EEG findings of increased slow activity in negative schizophrenia indicating organicity, it was hypothesized that neuroleptics decreasing delta/theta activity should be beneficial for schizophrenics with predominantly negative symptoms. Thus, a double-blind, clinical, psychometric and neurophysiological study was carried out in 40 hospitalized patients with unproductive schizophrenia (mean age: 31 years; ICD diagnoses: 295.0, 295.1 and 295.6) who were treated randomly either with the benzamide amisulpride (AMI; n = 19) or low doses of fluphenazine (FLU; n = 21). In the first 2 weeks the daily doses were 50 mg AMI or 2 mg FLU, respectively, from the third week on up to the sixth week 100 mg AMI and 4 mg FLU. Clinical evaluations, psychometry and EEG mapping were performed on day 1 (hours 0 and 4--acute effect), on day 14 (hour 0--subacute effect) and on day 42 (hours 0 and 4--chronic and superimposed effects). Three AMI patients discontinued therapy prematurely because of productive symptoms (days 14, 28 and 35), while in the FLU group 2 patients dropped out due to depressive symptoms (days 21, 28), 1 due to productive symptoms (day 35), 1 due to ineffectiveness (day 28), and 1 because of an akinetic crisis (day 6). Statistical evaluation demonstrated a significant improvement in the AMDP apathy and Andreasen SANS score in both groups with the patients remaining severely ill as rated by the CGI. FLU-treated patients needed significantly more anticholinergic medication than the AMI-treated group. Psychometric evaluation showed in regard to the noopsyche significant improvement after subacute, chronic and superimposed AMI, while FLU-treated patients showed significant improvement only after subacute treatment. AMI was significantly superior to FLU at the hours 0 and 4 of day 42. The thymopsyche improved after subacute, chronic and superimposed administration of both compounds with a significant superiority of AMI on days 14 and 42 (4 h postdrug). EEG mapping showed a decrease of delta/theta and increase of beta activity as well as an acceleration of the centroid after acute and superimposed AMI on day 42 as compared with baseline; FLU patients exhibited a decrease of delta/theta activity and an acceleration of the total centroid too, while alpha activity was augmented and beta activity tended to be reduced. Our study demonstrated that, in addition to the new benzamide AMI, FLU in low doses may also be regarded as a neuroleptic with activating properties and may be utilized in the treatment of schizophrenics with predominantly negative symptoms.

Adult↗
PubMed1991

Wittgenstein.

Explore the source record for details and available documents.

Humans↗
PubMed1991

Dopamine D2 receptor imaging with SPECT: studies in different neuropsychiatric disorders.

The purpose of the present study is to visualize and quantify dopamine D2 receptors in the living human brain using an 123I-labeled ligand and the single photon emission computerized tomography (SPECT) technique. S-(-)-Iodobenzamide [S-(-)-IBZM] has been shown to be a highly selective ligand with high affinity for D2 receptors in experimental studies. Five millicuries (185 MBq) of 123I-labeled S-(-)-IBZM was administered intravenously to 12 control subjects, 22 parkinsonian patients under L-Dopa therapy, 12 parkinsonian patients without L-Dopa, 10 unmedicated patients with Huntington's disease, and 12 patients under different neuroleptics. Data collection with a rotating double-head scintillation camera started 1 h after injection and lasted for 50 min. In a semiquantitative approach, a ratio was calculated between mean counts per pixel in the striatum and a region in the lateral frontal cortex, which was 1.74 +/- 0.10 in the control group. A marked reduction of this ratio was found in patients with Huntington's disease (1.38 +/- 0.12; p = 0.0001), no significant changes in untreated parkinsonian patients (1.67 +/- 0.14), but a reduction in L-Dopa-treated cases (1.59 +/- 0.13; p = 0.0014). A curvilinear relationship was found between total daily dose of neuroleptics and the reduction of this ratio. Estimated receptor blockade under full neuroleptic treatment was 75-80%. S-(-)-IBZM binding was reduced with increasing age (p less than 0.01). Specific binding was reduced markedly when the racemic mixture of IBZM was used, and no specific binding was seen with the R-(+)-isomer, demonstrating the stereoselectivity of IBZM binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Predicting course and outcome in delusional psychoses.

Eighty-four of 90 patients with delusional syndromes of different nosological attribution underwent a 7-year follow-up. From 179 items covering the whole spectrum of psychiatric description of index examination, 20 were found to be statistically significant in predicting different aspects of course and outcome by stepwise discriminant analysis. Course and outcome were defined by 6 criteria (course of illness, course of delusion, development of deficiency, length of inpatient care, adequate activity and social adjustment) encompassing separate (but only partly independent) aspects of a disorder. In contrast to the literature, clinical and psychopathological variables have major prognostic weight for different psychopathological as well as psychosocial aspects of outcome. Ten of the 20 significant items cover psychopathology, 4 pre-index course, 3 precipating events, 2 data from childhood, and 1 premorbid personality. Our results stress the importance of sensitive data collection and a clear separation of different outcome variables.

Adolescent↗
PubMed1990

EEG-brain mapping in schizophrenics with predominantly positive and negative symptoms. Comparative studies with remoxipride/haloperidol.

EEG brain maps obtained in 48 drug-free hospitalized schizophrenics diagnosed according to DSMIII demonstrated significant differences as compared with normal controls characterized by a decrease of alpha-1 activity, increase of beta activity and acceleration of the centroid. These findings suggest a state of sustained hyperarousal in schizophrenia. While the patients with negative schizophrenia showed a bi-temporal and frontal augmentation of delta/theta activity, patients with florid symptomatology exhibited just the opposite findings. Alpha-1 activity was attenuated, beta activity augmented in both groups with the findings more pronounced in the positive schizophrenia group. The increase of slow activity suggests an organic factor in the pathogenesis of the negative syndrome, which was supported by correlation maps between EEG measures and the apathy syndrome as measured by the AMDP system. Treatment of schizophrenics with predominantly positive symptoms with 2 different neuroleptics such as remoxipride and haloperidol resulted also in differential effects on brain activity: while haloperidol augmented delta/theta and alpha activity and decreased beta activity, remoxipride produced a decrease of slow and increase of beta activity as well as an acceleration of the centroid suggesting vigilance-promoting properties of the drug. These differential effects on the neurophysiological level were also reflected at the behavioural one evaluated by psychometry, while global clinical evaluation showed, as expected, similar improvement with both drugs (apart from extrapyramidal side effects being significantly more pronounced after haloperidol than remoxipride). Our findings suggest that brain electrical signal topography is a promising method in regard to a better understanding of pathogenesis and treatment in schizophrenia.

Adult↗