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Biomedical subjects

W W Fleischhacker

Publications and source records attributed to W W Fleischhacker.

At least 73 records · Page 4Linked to original sources
PubMed1995

A comparison of European and American dosing regimens of schizophrenic patients on clozapine: efficacy and side effects.

We present a comparison of the results from two studies of patients on clozapine. The American study (n = 84; Hillside Hospital, Glen Oaks, NY) and the European study (n = 63; Innsbruck University Clinics, Innsbruck, Austria) both examine efficacy and side effects in schizophrenic patients on this atypical neuroleptic. There is a very substantial difference in the dosing regimen used on both continents and this is reflected in the studies reported. A question with major clinical implications is whether the higher doses commonly used in the United States lead to a better outcome or a different profile of side effects. Outcome as a function of serum concentration will be examined. Results confirm a lower dose, lower clozapine blood level, and a lesser degree of side effects in the Austrian cohort when compared to the American sample. Surprisingly, the clinical efficacy of the lower dosing regimen was superior to the higher dose. Reasons for this anomaly are explored.

Adult↗
PubMed1994

Negative symptoms in schizophrenia: considerations for clinical trials. Working group on negative symptoms in schizophrenia.

There is little agreement about the methodology of clinical trials of antipsychotic drugs in patients with negative symptoms. A literature review revealed wide variation in experimental design, rating scales and study duration. This reflects differing views as to the definition and response to treatment of negative symptoms. Some degree of standardization would improve comparability of studies and aid the development of new compounds. Patients included in such studies should have displayed negative symptoms for at least 6 months. Depressive symptoms, positive schizophrenic symptoms and extrapyramidal signs may all influence or be confused with negative symptoms and may respond to treatment; they should be at a low level at baseline and should be measured during the study period. Studies should last at least 8 weeks. Several scales are available for measuring negative symptoms and are reviewed; a global impression score should be used additionally.

Clinical Trials as Topic↗
PubMed1994

EEG alterations in patients treated with clozapine in relation to plasma levels.

It is well known that psychotropic drugs can induce EEG alterations. Dose dependence seems established; however, there are no data concerning the impact of plasma levels. The authors investigated the influence of clozapine plasma levels on the frequency of EEG alterations. Data from 29 inpatients (18 male, 11 female, 31.7 +/- 10.2 years) receiving clozapine in a dose range between 25 and 600 mg were collected prospectively. There was no psychotropic or anticholinergic comedication. All patients had normal EEGs before taking clozapine. Fifteen patients showed pathological changes (group 2) and 14 no changes (group 1). Discriminant analysis showed that EEG changes are dependent on plasma levels (P = 0.0009, plasma levels in group 1 mean 81.6 ng/ml, +/- SD 64.6, in group 2 235.7 ng/ml, +/- 169.8). A total of 72.4% of the patients were correctly classified as having either pathological EEG changes or none by this analysis. Variables such as dose, age, sex, weight and duration of treatment were not statistically relevant. It can therefore be suggested that clozapine plasma levels are a valid indicator for the appearance of electrophysiological reactions.

Adult↗
PubMed1994

Antipsychotic maintenance treatment of schizophrenia patients: is there a consensus?

We obtained pharmaco-epidemiologic data regarding the antipsychotic maintenance treatment (AMT) of schizophrenia patients through a postal survey sent to all Austrian psychiatrists and neurologists. Drug therapy was considered the most important therapeutic approach in the long-term management of schizophrenia. However, the majority of the respondents clearly were not satisfied with the current status of scientific knowledge about dosage and duration of AMT. Single-drug treatment with antipsychotics was preferred by the respondents; oral and depot neuroleptics were used with equal frequency. Haloperidol was the oral drug most frequently mentioned as first choice (44% of the respondents), followed by clozapine (14.1%) and thioridazine (9.2%). The proposed mean daily doses showed striking variations among respondents. The proposed mean length of maintenance treatment in first-episode patients was 7.3 months; in multi-episode patients, it was 20.1 months. The results show considerable variation in physicians' attitudes toward AMT.

Administration, Oral↗
PubMed1994

Assessment of the alcohol withdrawal syndrome--validity and reliability of the translated and modified Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-A).

The alcohol withdrawal syndrome is a common phenomenon in psychiatric hospital care. Not only treatment strategies, but also the evaluation of the syndrome, are discussed controversially. The most widely used instrument is the Clinical Institute Withdrawal Assessment-Alcohol (CIWA-A) and the succeeding CIWA-Ar. We modified the CIWA-A and translated it into German. Validity and reliability of the modified and translated scale were analysed by several psychological tests as well as different somatic measures in 31 patients. The German version appears to be a valid and reliable instrument for the assessment of alcohol withdrawal syndrome useful for clinical routine as well as treatment trials.

Alcohol Withdrawal Delirium↗
PubMed1994

Compliance with antipsychotic drug treatment: influence of side effects.

In addition to other factors such as type and duration of treatment, patient- and illness-related variables and other psychosocial features, side effects are known to exert a significant influence on the compliance with antipsychotic treatment. This has been demonstrated for extrapyramidal motor side effects and akathisia, sedation, weight gain and sexual dysfunctions. Other adverse events interfering with the patients' social roles also interfere with the patients' willingness to comply with treatment. It is important to acknowledge this not only in the acute treatment of schizophrenia but especially during maintenance and prophylactic treatment. Compliance can be considerably improved by a) adequately informing the patient about the risks and nature of side effects and b) by recognizing and treating side effects, since prevention of adverse events is not easily achieved. An underestimation of the influence of side effects on compliance will often lead to treatment failures that are erroneously attributed to treatment resistance.

Adult↗
PubMed1994

Clozapine-induced transient white blood count disorders.

BACKGROUND: The aim of the study was to shed more light on the incidence and course of clozapine-induced transient white blood count (WBC) disorders. METHOD: In an analysis of our clozapine drug monitoring program, we evaluated the data of 68 patients receiving clozapine for the first time. Incidence rates were calculated by actuarial life table analysis. The potential influence of sex, age, dose, and plasma level was evaluated using discriminant analysis. RESULTS: Two patients developed progressive neutropenia, leading to agranulocytosis in one case. We also found the following transient hematologic dysfunctions: neutropenia (22.0%), eosinophilia (61.7%), and leukocytosis (40.9%). One patient showed chronic leukocytosis. Additionally, minor changes in the number of lymphocytes, monocytes, and basophilic granulocytes were detected in the study population. CONCLUSION: Hematologic side effects are frequently induced by the atypical antipsychotic clozapine. Next to agranulocytosis, a progressive and potentially lethal hematologic adverse effect, most of the WBC disorders are transient and appear to be harmless.

Actuarial Analysis↗
PubMed1994

Clozapine dose in the United States and Europe: implications for therapeutic and adverse effects.

The report (1) provides an overview of clozapine doses used in trials conducted in Europe and the United States, (2) compares data on efficacy, and (3) compares side effects of clozapine from recent European and U.S. investigations. The reviewed European trials used a mean dose of 283.7 mg/day, while the mean dose in the U.S. studies was 444 mg/day. Even though the mean doses used in the United States are considerably higher than those used in Europe, the response rates for the two continents are strikingly similar. The main differences in a comparison of two samples evaluated in New York and Innsbruck were found in the prevalence of seizures (Innsbruck, 0%; United States, 7.1%) and confusion (Innsbruck, 0%; United States, 14%). Excitement was less prevalent in the U.S. study. The data presented appear to suggest that a lower dose of clozapine may be as effective as a higher dose in the management of treatment-resistant schizophrenic patients and may cause fewer side effects.

Akathisia, Drug-Induced↗
PubMed1994

A multicenter double-blind trial of paroxetine versus amitriptyline in depressed inpatients.

The phenylpiperidine derivative paroxetine is a selective serotonin reuptake inhibitor. In a double-blind 6-week trial, paroxetine was compared with amitriptyline in hospitalized patients suffering from major depression (DSM-III). One hundred fifty-three patients were enrolled in the study in seven centers in Austria and Germany. Results showed similar efficacy of both drugs after 6 weeks. The differences between groups in Montgomery-Asberg Depression Rating Scale and Clinical Global Impression ratings did not reach statistical significance at any time. Side effects were distributed similarly but with a significantly higher incidence of anticholinergic effects in patients treated with amitriptyline (p < or = 0.001), whereas agitation and insomnia were registered more often in the paroxetine group. This study supports the antidepressive efficacy of paroxetine in a sample of severely depressed inpatients.

Adolescent↗
PubMed1994

Carbamazepine in the prophylaxis of major depression: a 5-year follow-up.

BACKGROUND: The prophylaxis of unipolar depression is still controversial. Some physicians prefer lithium, others maintenance treatment with antidepressants. The role of carbamazepine remains unclear. Only a few patients have been described in the literature; most are lithium nonresponders or rapid cyclers. METHODS: In an open-label naturalistic study, 15 patients suffering from major depression with melancholia (DSM-III, 296.2, 296.3) and receiving long-term prophylaxis with carbamazepine were followed for 5 years. Four had been pretreated with lithium without satisfactory effects, 11 were prophylaxis naive. We compared the number of depressive episodes before and during carbamazepine treatment. RESULTS: The mean time span patients received carbamazepine was 49.5 months. Seventy-three percent (11 of 15) of the patients gained substantial benefit from carbamazepine. Side effects were infrequent. CONCLUSION: Our results encourage further controlled and prospective studies using carbamazepine for maintenance treatment of patients with unipolar major mood disorder.

Adult↗
PubMed1993

Effects of clozapine on hematopoiesis and the cytokine system.

Using a bioassay for hematopoietic progenitor cells we looked for mechanisms causing clozapine induced neutropenia and agranulocytosis. Micro-agar-cultures of normal peripheral blood mononuclear cells (MNC) of eight patients currently treated with clozapine and of eight probands not receiving any kind of pharmacological treatment were incubated with increasing concentrations of clozapine (0, 7.5, 15, 30 micrograms/ml). Erythropoiesis and megakaryopoiesis were totally unaffected by clozapine. A biologically relevant suppression of granulopoiesis (CFU-GM) could only be shown in cultures incubated with 30 micrograms/ml clozapine. Cytokine analysis presented a strictly dose-dependent suppression of GM-CSF and neopterin release in all cultures. There was no difference between patients and controls at any clozapine concentration. The data support a possible role for cytokines as one mediator of the agranulocytosis producing effects of clozapine.

Biopterins↗
PubMed1993

Are patterns of benzodiazepine use predictable? A follow-up study of benzodiazepine users.

A sample of 171 patients taking benzodiazepines (BZDs) who had been investigated in 1988 was followed up in 1991. From 140 patients who were still alive and willing to participate, 25% had stopped BZDs after an average duration of intake of 34 months. Of the 105 persons still taking a BZD, 37% were taking the same dose, 26% had reduced the dose and 37% had increased it. Characteristics of BZD long-term users and patients potentially at risk for abuse and/or dependence that were established from the 1988 data were reexamined: patients with continued BZD use more often suffered from somatic illness which often had deteriorated, they had a longer duration of intake and used higher daily doses. In most cases the indication was insomnia. Patients with a clinically relevant dose increase were more often males, frequently found to be dependent on alcohol and/or illegal drugs.

Adult↗
PubMed1993

[Clozapine in long-term treatment of schizophrenic patients].

Clozapine has advantages over standard antipsychotics in refractory schizophrenia. Studies on the efficacy of clozapine in the maintenance treatment are sparse and suffer from methodological limitations. Despite this fact clozapine ranked second in a survey dealing with the preference of this antipsychotic in the long-term treatment of schizophrenia. Doctors report on using a mean of 130 mg/d in this indication which is considerably less than the doses used in most of the published long-term trials. The discrepancy between the popularity of clozapine and the lack of sound empirical data on its long-term efficacy is discussed.

Attitude of Health Personnel↗