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W W Fleischhacker

Publications and source records attributed to W W Fleischhacker.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Problems in evaluating new antipsychotic drugs].

A number of novel antipsychotics were registered and introduced into clinical practice in the last decade. These include olanzapine, quetiapine, risperidone, sertindole and zotepine as well as ziprasidone, which is still in the registration process. It quickly became apparent, that it is not always easy to translate results from phase II and III clinical trials into everyday clinical practice. In this context, we discuss methodological aspects that mainly deal with selection of patients for clinical trials and clinical trial methodology. Next to that, an overview of the current knowledge concerning novel antipsychotics is given. There is no doubt that these drugs broaden the therapeutic spectrum made available to patients suffering from schizophrenia. On the other hand, it is evident that there is still a need for a critical evaluation of the risk-benefit-ratio of novel antipsychotics. Clinical psychiatrists also face the challenge to modify some of the traditional treatment approaches. These prerequisites will allow the embedding of novel antipsychotics into modern integrative treatment concepts of schizophrenia.

Antipsychotic Agents↗
PubMed1998

[Compliance problems in treatment of schizophrenic patients].

Compliance is the degree of adherence to an appropriate medical advise. Especially in longterm treatment, therapeutic success depends largely on patient compliance. In the treatment of schizophrenia with antipsychotic agents a non-compliance rate up to 80% is the reason for the difference between the relatively good outcome of controlled treatment studies and the bad results in clinical reality. 4 groups of variables can be identified, which influence compliant behaviour: patient-related factors, factors related to the patients environment, physician-related factors, and medication-related factors. Possibilities to ameliorate the compliance of schizophrenic patients during long-term therapy are discussed.

Antipsychotic Agents↗
PubMed1997

[Railroad suicides and attempted suicides in Austria 1990-1994. Extending the hypothesis mass media transmission of suicidal behavior].

Suicide on railways (either by being run over by or jumping in front of a train) is one of the "hardest' suicide methods. In Austria, 617 suicides or attempted suicides on railways were registered between 1990 and 1994. This amounts to 5.73% of all suicides committed in this period with women showing a higher percentage than men. In both men and women there was a predominance of younger age groups; the mean age was higher in women than in men (48.0 vs 40.4 years). There was a significant increase in suicides or attempted suicides on railways after a television report on the stress suffered by train drivers concerning possible suicides. Persuading the mass media to treat the subject of "suicide' with reserve and with greater caution, even when not presenting a distinct suicide model, may be of importance in general suicide prevention.

Adolescent↗
PubMed1997

Risk factors for the development of neuroleptic induced akathisia.

Neuroleptic induced akathisia (NIA) is a common and distressing side effect of antipsychotic treatment. Incidence rates are reported to be between 25% and 75%, depending on criteria used for diagnosis. The results of our four week prospective naturalistic study are based on the assessment of 73 inpatients, which were started on antipsychotic medication in one of the inpatient units of the Department of Psychiatry. NIA was rated with the Hillside Akathisia Scale. Assuming that both, objective as well subjective phenomena are necessary for a valid diagnosis of NIA, we calculated an incidence rate of 22.4%. 75% of all NIA cases occurred within the first three days of antipsychotic treatment. When attempting to determine risk factors for the development of NIA, we found a significant influence of dose increase in the first days of treatment.

Adult↗
PubMed1997

Hepatotoxicity of clozapine.

Two hundred thirty-eight patients treated with either haloperidol or clozapine were investigated to shed more light on the incidence and severity of antipsychotic-induced liver enzyme increase. Serum glutamic-pyruvic transaminase (SGPT) increase was most frequently seen in both treatment groups. When analyzing the incidence rates for patients with increased liver enzyme values (serum glutamic-oxaloacetic transaminase, SGPT, gamma-glutamyl transpeptidase) that were higher than twice the upper limit of the normal range, clozapine-treated patients showed an SGPT increase (37.3%) significantly more frequently than patients treated with haloperidol (16.6%). Both patients with higher clozapine plasma levels and male patients were at a higher risk for an SGPT increase. At least 60% of the increase of the different enzymes remitted within the first 13 weeks of treatment. In general, the authors conclude that clozapine-induced liver enzyme elevation seems to be a common and mostly transient phenomenon.

Adult↗
PubMed1997

Drug treatment of schizophrenia in the 1990s. Achievements and future possibilities in optimising outcomes.

The current state of the art of the pharmacological treatment of schizophrenia, and a review of the latest findings in antipsychotic drug development are presented. A first step in optimising treatment is an increase in the awareness and implementation of existing treatment standards. The introduction of clozapine challenges the view that all antipsychotics are of similar efficacy; the drug has an established superiority over some of the traditional antipsychotics in treatment-resistant patients. Newer agents such as zotepine, risperidone, quetiapine, olanzapine and sertindole, which have a lower risk of producing extrapyramidal motor symptoms, have been developed in the wake of clozapine. While it is still common to switch nonresponding patients to an antipsychotic of a different chemical class, clozapine treatment remains the only strategy based on sound scientific evidence in these patients, although the novel antipsychotics give rise to hope. Alternatively, combination treatment with benzodiazepines, lithium or an anticonvulsant has been employed. If treatment with a depot antipsychotic is planned, it is advisable to start a patient on the oral form of the same drug in order to obtain dose requirements and tolerability information of the drug in that patient. Long term maintenance therapy is crucial and continuous monitoring for the development of adverse effects essential.

Humans↗
PubMed1996

CSF of neuroleptic-naive first-episode schizophrenic patients: levels of biogenic amines, substance P, and peptides derived from chromogranin A (GE-25) and secretogranin II (secretoneurin).

Lumbar cerebrospinal fluid (CSF) was collected from controls and neuroleptic-naive patients with their first acute schizophrenic episode. The CSF was analyzed for several biogenic amines and their metabolites [dopamine,dihydroxyphenylacetic acid (DOPAC), noradrenaline, 5-hydroxytryptamine (5-HT), 5-hydroxyindolacetic acid (5-HIAA)]. For these transmitters, which are stored and secreted from synaptic vesicles, there was no significant difference between controls and schizophrenic patients. As constituents of large dense-core vesicles substance P (SP) and GE-25 (derived from chromogranin A)-and secretoneurin (derived from secretogranin 11)-immunoreactivities were determined. SP-like immunoreactivity levels did not differ between controls and patients; however, GE-25 was elevated and especially the GE-25/secretoneurin ratio was significantly (p < .001) higher in patients. Characterization of the immunoreactivities by high-performance liquid chromatography did not reveal any difference between patients (n = 3) and controls in the processing of the two proproteins chromogranin A and secretogranin II. These data indicate that proteolytic processing of the two widespread constituents of large dense-core vesicles, i.e., chromogranin A and secretogranin II, is not altered in schizophrenic patients. The increase in the chromogranin A /secretoneurin ratio in schizophrenic patients deserves further investigation in order to elucidate its possible pathogenetic significance.

Adult↗
PubMed1996

Comparison of acamprosate and placebo in long-term treatment of alcohol dependence.

BACKGROUND: About 50% of alcoholic patients relapse within 3 months of treatment. Previous studies have suggested that acamprosate may help to prevent such relapse. The aim of our study was to assess the efficacy and safety of long-term acamprosate treatment in alcohol dependence. METHODS: In this multicentre, double-blind, placebo-controlled study, we recruited 455 patients, aged 18-65 years, with chronic or episodic alcohol dependence. Patients were randomly allocated treatment with acamprosate (1998 mg daily for bodyweight > 60 kg; 1332 mg daily for < or = kg) or placebo for 360 days. Patients were assessed on the day treatment started and on days 30, 90, 180, 270, and 360 by interview, self-report, questionnaire, and laboratory screening. Patients were classified as abstinent, relapsing, or non-attending. Time to first treatment failure (relapse or non-attendance) was the primary outcome measure. FINDINGS: Seven patients were excluded from the intention-to-treat analysis because they did not attend on the first treatment day and therefore received no medication. The acamprosate (n = 224) and placebo (n = 224) groups were well matched in terms of baseline demographic and alcohol-related variables. 94 acamprosate-treated and 85 placebo-treated patients completed the treatment phase: of those withdrawn, 104 (52 in each group) relapsed, 69 (33 vs 36, respectively) were lost to follow-up, 63 (31 vs 32) refused to continue treatment, 16 (15 vs 11) had concurrent illness, three (two vs one) died, ten (six vs four) had adverse side-effects, one (acamprosate treated) received the wrong medication, and three (placebo treated) were non-compliant. The proportion without treatment failure was higher in the acamprosate than in the placebo group throughout the treatment period (p < 0.001, Mantel-Cox). At the end of treatment, 41 (18.3%) acamprosate-treated and 16 (7.1%) placebo-treated patients had been continuously abstinent (p = 0.007). Mean cumulative abstinence duration was significantly greater in the acamprosate group than in the placebo group (138.8 [SD 137.5] vs 103.8 [119.0] days; p = 0.012). 148 patients (79 acamprosate, 69 placebo) completed 27 months follow-up: 27 (11.9%) acamprosate-treated and 11 (4.9%) placebo-treated patients remained continuously abstinent, and the mean cumulative abstinence duration was 230.8 days (259.1) and 183.0 days (235.2), respectively. Apart from occasional diarrhoea, there was no difference in side-effects between groups. INTERPRETATION: Acamprosate is an effective and well-tolerated pharmacological adjunct to psychosocial and behavioural treatment programmes for treatment of alcohol-dependent patients.

Acamprosate↗
PubMed1996

Does eosinophilia predict clozapine induced neutropenia?

The atypical antipsychotic clozapine carries a high risk of inducing agranulocytosis. We attempted to investigate whether eosinophilia during clozapine treatment has predictive value for subsequent neutropenia/agranulocytosis. One hundred and seventy-seven patients were studied in a prospective naturalistic design using haloperidol as the reference compound. Clozapine was found to differ from haloperidol in respect to their influence on neutrophil granulocytes. In the clozapine group patients with eosinophilia showed a decrease in neutrophil count (less than 2000/mm3 neutrophil granulocytes) significantly more often than patients without eosinophilia.

Adolescent↗
PubMed1995

Extrapyramidal side effects of clozapine and haloperidol.

Neuroleptic-induced extrapyramidal side effects (EPS) were evaluated in 92 patients treated with clozapine for the first time and 59 patients treated with haloperidol followed in a drug monitoring program. Side effects were measured by the Columbia University Rating Scale, the Simpson Dyskinesia Scale and the Hillside Akathisia Scale. The cumulative incidence rate for tremor was found to be 24.4% in the clozapine group and 39.3% in the haloperidol group. This did not amount to a statistically significant group difference. Bradykinesia was observed in 21.8% of the patients treated with clozapine and in 47.7% of the patients of haloperidol (P = 0.011). In the clozapine group the akathisia incidence rate was 5.6%, whereas haloperidol patients showed a higher rate of 31.7% (P = 0.005). Our results show higher incidence rates of tremor and bradykinesia during clozapine treatment than previous studies. We conclude that clozapine is not entirely free of EPS, but they are usually less severe and of a different quality than side effects induced by typical antipsychotics.

Adult↗
PubMed1995

Differential effects of the D1-DA receptor antagonist SCH39166 on positive and negative symptoms of schizophrenia.

In the present open study the effects of the D1-dopamine antagonist SCH 39166 on positive and negative symptoms of schizophrenia (DSM-IIIR) were investigated. SCH 39166 was given orally according to a fixed dosage schedule (day 1: 25 mg b.i.d; day 4: 50 mg b.i.d.; day 7: 100 mg b.i.d.; day 18: 200 mg b.i.d.; day 21: 225 mg b.i.d.). Seven patients completed 2 weeks, and five patients completed the study. The reason for premature withdrawal was lack of efficacy or refusal to take SCH 39166. In none of the patients a reduction of the BPRS or CGI score was found. As measured with the PANSS, a significant reduction was observed in the score of the negative subscale, whereas the positive symptoms scale and general psychopathology score remained unaffected. Akathisia, rigidity and hypokinesia were reported occasionally, although only mild in severity. The results of the present study do not support the hypothesis that D1-dopamine antagonists are clinically effective antipsychotics in schizophrenia, considering the fact that SCH 39166 had no effect on positive symptoms. The present study provides circumstantial evidence for an effect of SCH 39166 on negative symptoms.

Administration, Oral↗
PubMed1995

Weight gain induced by clozapine.

Patients were investigated to gain more insight into the incidence and time course of clozapine induced weight gain (n = 81) and to compare weight gain in patients treated with clozapine (n = 31) with that of patients treated with standard antipsychotics (haloperidol, n = 11). 35.7% of the patients treated with clozapine gained weight according to our definition. If patients gained weight on clozapine this side effect was apparent within the first 12 weeks of treatment. Deviation from normal body weight at the beginning of treatment showed a significant influence on weight gain. Sex, severity of illness, comedication, mean clozapine dose and degree of improvement did not show an influence on this side effect. Weight increase was significantly higher in patients treated with clozapine than in patients treated with haloperidol.

Adult↗
PubMed1995

Adverse effects of antipsychotic drugs.

The side effects of antipsychotic drugs have always been a major concern for clinicians and the appreciation of their importance in the treatment of schizophrenia has increased steadily over the years. Epidemiological studies as well as trials of the prevention and treatment of antipsychotic side effects are the consequences of this development. Results of these studies also have important implications for improving compliance and quality of life in schizophrenic patients. Thus, side effects research has made the treatment of schizophrenia not only safer but also more effective. Next to a brief overview of some of the more important adverse events and their treatment, we will also discuss these effects in the context of compliance, treatment response and the influence of anti-EPS drugs.

Akathisia, Drug-Induced↗
PubMed1995

Tardive dyskinesia prevalence rates during a ten-year follow-up.

We followed up patients in the State Psychiatric Hospital Mauer-Ohling, Mauer-Ohling, Austria, who had been examined in 1982 to determine the prevalence of tardive dyskinesia (TD). Of the 861 patients examined in 1982, 270 were still in hospital 10 years later. Only these patients were included in our study. The SKAUB (Skala für abnorme unwillkürliche Bewegungen, i.e., The German version of the Abnormal Involuntary Movement Scale) was used to quantify the occurrence of TD. The prevalence rate of TD was 3.7% in 1982 and 12.7% in 1992. The 1992 prevalence rate in patients who had not shown TD symptoms in 1982 was 11.4%. The major risk factor for TD was advanced age.

Adult↗
PubMed1995

New drugs for the treatment of schizophrenic patients.

Conventional neuroleptics are widely accepted as being effective against the positive symptoms of schizophrenia, but do not benefit all patients. Furthermore, they are relatively ineffective against negative symptoms and cognitive disorders, and most have unpleasant side effect profiles. New strategies for treating schizophrenia include the development of dopamine antagonists with high selectivity for different subtypes of dopamine receptors, dopamine partial agonists, antagonists at different serotonin (5-hydroxytryptamine; 5-HT) receptor subtypes, drugs with mixed pharmacological profiles and drugs which modify transmission via amino acids or peptides in the brain. The prospect is that some of these strategies will lead to the introduction of new drugs and that some of these will become the standards against which future drugs will be compared. The search for new drugs and their use in clinical practice will also lead to developments in our knowledge and understanding of schizophrenia.

Affective Symptoms↗