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A Hillert

Publications and source records attributed to A Hillert.

At least 19 recordsLinked to original sources

Long-term effects of the substituted benzamide derivative amisulpride on baseline and stimulated prolactin levels.

In the present study, we investigated the long-term effects of treatment with amisulpride, a substituted benzamide derivative, as compared with the effects of treatment with flupenthixol, a thioxanthene, on the prolactin levels in schizophrenic patients. After completing 6 weeks of medication with either amisulpride or flupenthixol, the patients entered a long-term maintenance treatment with amisulpride 200-600 mg/day or flupenthixol 5-15 mg/day for a maximum of 12 months with a subsequent drug-free follow-up until month 15. Eighteen initially included patients were still participating in the study at month 6. In the flupenthixol group, only 1 patient treated reached month 12, and none of the patients reached month 15. For the amisulpride treatment group, months 12 and 15 were completed by 9 and 6 patients, respectively. After 1, 3, 6, and 12 months of treatment, and finally 3 months after cessation of treatment, the basal and thyrotropin-releasing hormone-stimulated secretions of prolactin were investigated. The prolactin plasma levels were elevated in both treatment groups during the course of maintenance treatment with a maximum effect at month 1. Flupenthixol treatment initially raised the prolactin levels about two- or threefold, and a subsequent decline during months 3 and 6 occurred. However, only the changes for month 1 reached the level of a statistical trend. The prolactin secretion was initially increased over tenfold by amisulpride. The prolactin levels at months 1, 3, 6, and 12 were significantly elevated as compared with the baseline values. A continuous decline of prolactin levels in both treatment groups occurred over the course of the next months. The prolactin response after the thyrotropin-releasing hormone challenge was not significantly changed over the long-term course. Notably, in the amisulpride group, 3 months after cessation of treatment at month 12, the elevated levels of prolactin returned to baseline at month 15. In summary, amisulpride demonstrated more pronounced effects than flupenthixol on the prolactin levels. However, the findings indicate also that treatment with amisulpride at clinically effective doses can be achieved at significantly lower prolactin levels during the long-term maintenance phase than during the prior acute phase.

Adult↗

[Therapeutic programmes focusing on job related problems - which psychosomatic patients should participate?].

The necessity to offer special therapeutic programmes focusing on job related problems in psychosomatic rehabilitation has become increasingly evident. Which patients should participate in such programmes? This question has not yet been discussed with regard to its theoretical and methodological implications. In clinical practice the decision has been based on the therapists evaluation. 105 patients, consecutively admitted in a psychosomatic hospital were interviewed with a screening questionnaire about their job related strains and the perceived interaction between symptomatology and job. According to the literature guidelines for inclusion of psychosomatic patients to a special work hardening programme were used. Therapists were asked to independently assign their patients to the programme. The overlap between the two procedures was small. While the guidelines focussed on a high level of job strain and the patient's motivation for a job-related therapeutic approach, the therapists' decision was based on duration of inability to work, impairments at work due to the symptoms, conflicts with colleagues at work and the patient's ability to perceive problems in a differentiated manner. Considering the problem of inclusion-criteria for a work hardening programme, the highly complex constellations behind routine therapeutic decisions in psychosomatic rehabilitation became evident. To integrate medical diagnosis, symptomatology, psychological models, job strain, the patient's social situation and values, is a neglected but important goal of rehabilitation sciences and should be a base for a concept guiding the development, evaluation and establishment of work related therapeutic programmes.

Adult↗

Neuroendocrine response to antipsychotics: effects of drug type and gender.

BACKGROUND: To study the influences of drug type and gender on the neuroendocrine response to neuroleptic treatment, we compared the endocrine actions of two neuroleptics with different receptor affinity profiles--a substituted benzamide, amisulpride, a selective D2-like dopamine antagonist; and a thioxanthene, flupenthixol, a mixed D1/D2-like antagonist also blocking serotonin, H1, and D1 receptors--on anterior pituitary hormone secretion in schizophrenic patients (DSM-III-R). METHODS: Blood was withdrawn at 15-min intervals to assess basal secretion of prolactin, growth hormone (GH), and thyroid-stimulating hormone (TSH). Four hundred micrograms of thyrotropin-releasing hormone (TRH) was injected i.v. to investigate drug effects on TRH-stimulated secretion of prolactin, TSH, and GH. RESULTS: Prolactin plasma levels were markedly elevated in both treatment groups. In female, but not in male patients, this elevation was significantly more pronounced under amisulpride than under flupenthixol. The prolactin response to TRH was significantly blunted by amisulpride only in male subjects. While basal TSH secretion was significantly increased by both compounds, TRH-stimulated TSH secretion was elevated only in patients treated with amisulpride. Low basal prolactin levels predicted improvement of negative symptoms in patients treated with amisulpride. CONCLUSIONS: Amisulpride's more pronounced endocrine effects may be a reflection of its distinguished pharmacology and pharmacokinetics.

Adult↗

Amisulpride versus flupentixol in schizophrenia with predominantly positive symptomatology -- a double-blind controlled study comparing a selective D2-like antagonist to a mixed D1-/D2-like antagonist. The Amisulpride Study Group.

The benzamide amisulpride (ASP) is a selective D2-like dopamine antagonist, while flupentixol (FPX), a thioxanthene, blocks D2-like, D1-like and 5-HT2 receptors. To evaluate efficacy and safety of ASP and to investigate the importance of an additional D1-like antagonism for antipsychotic effects and extrapyramidal tolerability, a randomized double-blind multi- center study versus FPX as reference drug was performed for 6 weeks in 132 patients suffering from acute schizophrenia (DSM-III-R) with predominant positive symptomatology. Doses were initially fixed (ASP: 1000 mg/day; FPX: 25 mg/day) but could be reduced by 40% in case of side effects (mean daily doses: ASP: 956 mg; FPX: 22.6 mg). Intention-to-treat evaluation demonstrated significant improvement under both medications. The difference between the mean BPRS decreases of both treatment groups was 5.6 points (95% CI: 0.55; 10.65) in favour of ASP. According to CGI, 62% of patients in either drug group were treatment responders. ANCOVA analysis showed that reductions of BPRS (ASP: -42%; FPX: -32%) and SAPS (ASP: -78%; FPX: -65%) were more pronounced under ASP. Due to adverse events, significantly fewer ASP patients (6%) were withdrawn from the study (FPX: 18%). Extrapyramidal tolerability was better in the ASP group, as demonstrated by smaller increases in the Simpson-Angus Scale, the AIMS, and the Barnes Akathisia Scale in ANCOVA analyses with dosage as covariate. ASP appears to be as effective as FPX with regard to antipsychotic effects on positive schizophrenic symptomatology, while extrapyramidal tolerability is better. These conclusions have to be drawn cautiously, as dosage effects on outcome parameters cannot be entirely ruled out. The present results question the notion that additional blockade of D1-like receptors may be necessary to achieve sufficient antipsychotic effects or to improve extrapyramidal tolerability.

Adult↗

Risperidone versus haloperidol and amitriptyline in the treatment of patients with a combined psychotic and depressive syndrome.

In a multicenter, double-blind, parallel group trial, the efficacy of risperidone (RIS) was compared with a combination of haloperidol and amitriptyline (HAL/AMI) over 6 weeks in patients with coexisting psychotic and depressive symptoms with either a schizoaffective disorder, depressive type, a major depression with psychotic features, or a nonresidual schizophrenia with major depressive symptoms according to DSM-III-R criteria. A total of 123 patients (62 RIS; 61 HAL/AMI) were included; the mean daily dosage at endpoint was 6.9 mg RIS versus 9 mg HAL combined with 180 mg AMI. Efficacy results for those 98 patients (47 RIS; 51 HAL/AMI) who completed at least 3 weeks of double-blind treatment revealed in both treatment groups large reductions in the Positive and Negative Syndrome Scale-derived Brief Psychiatric Rating Scale (RIS 37%; HAL/AMI 51%) and the Bech-Rafaelsen Melancholia Scale total scores (RIS 51%; HAL/AMI 70%). The reductions in the Brief Psychiatric Rating Scale and the Bech-Rafaelsen Melancholia Scale scores in the total group were significantly larger in the HAL/AMI group than in the RIS group (p < 0.01), mostly because of significant differences in the subgroup of patients suffering from depression with psychotic features, whereas treatment differences in the other diagnostic subgroups were not significant. The incidence of extrapyramidal side effects as assessed by the Extrapyramidal Symptom Rating Scale was slightly higher under RIS (37%) than under HAL/AMI (31%). Adverse events were reported by 66% of RIS and 75% of HAL/AMI patients. The results of this trial suggest that the therapeutic effect of HAL/AMI is superior to RIS in the total group of patients with combined psychotic and depressive symptoms. However, subgroup differences have to be considered.

Adolescent↗

Public opinion on psychotropic drugs: an analysis of the factors influencing acceptance or rejection.

Widespread negative attitudes and irrational beliefs about psychotropic drugs held by the public affect patients' treatment compliance. This study was an attempt to identify factors influencing people's acceptance or rejection of psychotropic drugs. An opinion poll was taken by a representative group of 2,176 adults in Germany. In addition to their attitudes toward psychotropic and cardiac drugs and their ratings of perceived risks and benefits, they were also asked about their drug knowledge, their fear of losing self-control, and their fundamental political values. Our results show that even for the treatment of severe mental disease, psychotropic drugs generally are not well accepted compared to cardiac drugs. Psychotropic drugs are believed to cause significantly more severe side effects and provoke more fear of losing control compared with cardiac drugs. Knowledge about psychotropic drugs and experiences with patients suffering from mental disorders are rather limited. Therefore, other sources of information such as negatively tainted reports in the mass media have a significant impact on opinions about psychotropic drugs. Unexpectedly, negative media reports are even more important for the discrimination of distinct subtypes like "acceptors" and "rejecters" of psychotropic drugs than fundamental value orientation. It is recommended that educational and information measures must be enacted to achieve balanced presentation of psychotropic drugs, their effects, and their side effects in the mass media. Improved communication and linguistic elements used in psychotherapeutic settings should be integrated into biological psychiatry to improve understanding of the concepts of mental diseases and their treatment.

Adolescent↗

Psychopharmacological drugs as represented in the press: results of systematic analysis of newspapers and popular magazines.

The representation of mental diseases and psychopharmacological drugs in the media, especially in the press, is thought to be of great impact on people's opinions on the subject. During the course of one year, all articles about psychopharmacological drugs and cardiac drugs published in nineteen German newspapers were collected. All statements, together with related aspects, reasons for prescription, individual details of the patient, effects and side-effects, were registered and classified according to a key. The results show that, in contrast to 13% of the articles about cardiac drugs, half of the reports about psychopharmacological drugs deal primarily with the problems of side-effects and dependence the drugs may produce. There was much more critical comment and emotional emphasis used to characterize the psychopharmacological drugs. Only in 9% of articles was their therapeutic efficacy mentioned. Cardiac drugs are generally discussed objectively in a medical context and in 53% efficacy is emphasized. Psychopharmacological drugs are often mentioned in stories about prominent persons having a life crisis, taking drugs, turning to alcoholism, or in the context of social decline. Only in 3% of all articles about psychopharmacological drugs was it possible to identify a serious mental disease as the reason for prescription. The reasons for and implications of these findings, which mainly reflect the negatively biased image of psychopharmacological drugs in women's magazines (while they are treated relatively fairly in general newspapers) are discussed.

Cardiovascular Agents↗

The neuroendocrinological profile of roxindole, a dopamine autoreceptor agonist, in schizophrenic patients.

Roxindole is a potent autoreceptor-selective dopamine agonist with additional properties as a serotonin reuptake inhibitor and 5-HT1A agonist. In order to get more insight into its mode of action in various psychiatric populations, we evaluated the effects of subchronic roxindole treatment on pituitary and adrenal hormone secretion, i.e. release of prolactin, thyroid stimulating hormone (TSH), growth hormone (GH), luteinizing hormone (LH), and cortisol. Fifteen schizophrenic patients with positive and negative symptomatology, respectively, were treated with roxindole for 28 days. Both basal and thyrotropin releasing hormone (TRH) -induced prolactin secretion diminished significantly to 26.4% and 22.8% of baseline levels, respectively, under roxindole. Basal GH secretion was insignificantly elevated by 89%, whereas GH levels increased nearly 3-fold after stimulation by TRH. TSH levels decreased insignificantly to 57.5% of baseline levels, while TRH-induced TSH release was not affected by subchronic roxindole. Roxindole treatment influenced neither LH secretion nor cortisol release. Our results indicate that roxindole's dopaminergic actions might prevail over its serotonergic effects, at least as far as the regulation of anterior pituitary hormone secretion is concerned.

Adult↗

[Psychopharmaceutical drugs in the mass media. Results of a systematic analysis of text contents and images].

Mental diseases and psychopharmacological drugs are frequently discussed in newspapers and popular magazines. The representations are supposed to have a great impact on people's opinions on the subject. From 1 August 1991 to 31 July 1992 all articles about psychopharmacological drugs and cardiac drugs in 19 German newspapers were collected. All statements, effects and side effects, the reason for prescription, individual details about the patient and, according to this procedure, subjects and implications of the illustrations, were registered and classified according to a code book. In contrast to the articles about cardiac drugs, half of the psychopharmacological drug reports primarily deal with the problems of side effects the drugs may produce. There was much more critical comment and emotional emphasis used to characterize the psychopharmacological drugs. Only in 9% was their therapeutic efficacy mentioned. Cardiac drugs are generally discussed objectively in a medical context and their efficacy is emphasized. Psychopharmacological drugs are often mentioned in stories about prominent persons having a life crisis, taking drugs, or turning to alcoholism, in the sense of social decline. In only 3% of these articles could a serious mental diseases be identified as the reason for the prescription. Corresponding to the more prominent emotional emphasis of these articles, compared to the articles about cardiac drugs, more pictures, mainly of prominent persons or patients are used. However, the illustration seldom adds to information provided. The reasons for and implications of these findings and the significant differences between the distinct groups of newspapers are discussed.

Cardiovascular Agents↗

Pharmacokinetics and bioavailability of benperidol in schizophrenic patients after intravenous and two different kinds of oral application.

Pharmacokinetics and bioavailability of benperidol were determined in 13 schizophrenic patients after acute administration of 6 mg benperidol as an intravenous (i.v.) bolus injection, orally as liquid, and orally as tablets using a partially randomized cross-over design. Drug plasma levels were determined by high performance liquid chromatography with electrochemical detection and subjected to model independent pharmacokinetic analyses. After i.v. dosing the geometric means (mean-g) were 3.2 min for the distribution half-life, 5.80 h for the elimination half-life (t1/2 beta), 4.21 l/kg for the distribution volume, 7.50 h for the mean residence time (MRT), and 0.50 l/(h*kg) for the clearance. After oral administration as liquid and as tablet mean-g data for the time lag until the first appearance of measurable plasma concentrations were 0.33 and 1.1 h, mean-g t1/2 beta values were 5.5 and 4.7 h, respectively, mean-g tmax data were 1.0 h and 2.7 h, mean-g MRT values were 8.44 and 8.84 h, and mean-g Cmax maxvalues were 10.2 and 7.3 ng/ml. Differences between liquid and tablet administration were statistically significant for time lag, tmax, and Cmax. Mean-g absolute bioavailabilities were computed as 48.6% after liquid and 40.2% after tablet administration respectively. All parameters studied exhibited large intersubject variation. The plasma concentrations of the presumed metabolite "reduced benperidol" were found to be very low.

Administration, Oral↗

Plasma levels of benperidol, prolactin, and homovanillic acid after intravenous versus two different kinds of oral application of the neuroleptic in schizophrenic patients.

Plasma levels of prolactin (PRL) and the butyrophenone neuroleptic benperidol (BPD) were closely followed 0 to 48 h after acute application of 6 mg BPD as intravenous injection, orally as liquid, and orally as tablets in 12 schizophrenic patients using a partially randomized cross over design. Drug concentrations showed application specific pharmacokinetic behavior with complete elimination within 48 h. All three applications led to a biphasic PRL response with pronounced initial plasma PRL peaks returning to baseline levels within 48 h. The results suggest that after acute neuroleptic challenge BPD plasma levels as low as 2-3 ng/ml can be sufficient for complete depletion of pituitary PRL stores. This initial peak was followed by a PRL plateau about twice above pretreatment values indicating doubling of the PRL synthesis and secretion independent of supraeffective actual BPD concentrations. The PRL plateau persisted as long as BPD concentrations were above those levels which triggered the initial PRL response. As compared with the time of maximum concentrations (tmax) for BPD, the PRL tmax was later after i.v. injection, equal after liquid application, and earlier after tablet administration leading to pronounced application specific differences in shape, direction, and position of resulting hysteresis curves. Plasma levels of homovanillic acid (HVA) were not affected by BPD treatment. The PRL and HVA levels registered after acute doses of BPD indicated that the hormone responses were most likely the result of acute depletion of PRL stores and subsequent stimulation of hormone synthesis whereas it seemed unlikely that dopaminergic activities were relevant.

Administration, Oral↗

Roxindole, a dopamine autoreceptor agonist, in the treatment of positive and negative schizophrenic symptoms.

Twenty schizophrenic inpatients with either predominantly positive or predominantly negative symptoms were treated with the dopamine autoreceptor agonist roxindole in prospective open clinical trials. There was no antipsychotic effect in the subgroup with positive symptoms, whereas the subgroup with negative symptoms, especially those with the residual type of schizophrenia, showed a moderate but significant 20% reduction in total scores on the Scale for the Assessment of Negative Symptoms.

Dopamine Agents↗

[Attitude of medical students to treatment with psychotropic drugs. 1: Comparison between medical students and the general population].

The attitudes of medical students towards psychotropic drugs are compared with those of the general public. Students strike a more positive balance between the costs and benefits of this treatment method. Whereas there are no marked differences as concerns desirable effects both groups differ considerably in the assessment of the limitations and risk of undesirable side-effects with students being less sceptical in this respect. Also with regard to other attitudinal domains student's judgement is more favourable. However, this does not mean that there is not a remarkably large group which articulates reservations against the use of psychotropic drugs. Whereas the majority of the lay public considers psychotherapy in general as superior to psychopharmacotherapy most students tend to differentiate between the various forms of psychiatric disorder.

Adolescent↗

[Attitude of medical students to treatment with psychotropic drugs. 2: Change in attitude in the course of medical education].

Advanced medical students' attitude to psychotropic drugs is more positive than the lay public's view on that subject (see part I). The question arises if this is a result of the psychiatric and psychopharmacological knowledge students have acquired during their medical education or an effect of selection by which students already have a more positive opinion of psychotropic drugs before the commencement of their medical education. Our survey in three differently advanced groups of medical students (n = 323) was carried out with a questionnaire. In contrast to their scepticism concerning psychopharmacological treatment students in the beginning of their medical education estimate others than psychotropic drugs ly than the lay public. This may be explained by a beginning identification with the model of a quickly and effectively treating doctor. In the course of medical and especially psychiatric and psychopharmacological education, there is a tendency to a more differentiated and positive view on the effects of psychotropic drugs although the generally critical attitude persists.

Adolescent↗

Risperidone in the treatment of disorders with a combined psychotic and depressive syndrome--a functional approach.

In vitro receptor-binding profiles and in vivo pharmacological studies have shown risperidone to be a potent mixed serotonin-S2 dopamine-D2-like receptor antagonist. While anti-D2 activity may relate to the antipsychotic potency of neuroleptic drugs, an antidepressive efficacy of substances with anti-S2 activity has been suggested. In an open pilot-study, ten patients with schizodepressive disorders or a DSM-III-R diagnosis of psychotic major depressive episodes were treated with risperidone (2-10 mg/d) for six weeks. Weekly psychopathological evaluation was performed, including BPRS, SANS, SAPS, VAS scales, and AIMS and UKU for the assessment of side-effects. Generally, the psychotic syndrome (BPRS, SANS and SAPS) decreased markedly in all patients; seven patients also showed a clinically significant improvement of depressive symptoms (BPRS). Except for two patients who needed biperiden because of extrapyramidal side-effects, the tolerance of risperidone was good. The antipsychotic and antidepressive properties of risperidone shown in our pilot study are promising enough to merit full double-blind controlled trials for further evaluation of its therapeutic value in this broad spectrum of psychiatric disorders.

Adult↗

Determination of benperidol and its reduced metabolite in human plasma by high-performance liquid chromatography and electrochemical detection.

An isocratic high-performance liquid chromatographic method with electrochemical detection for the quantification of benperidol and its suggested reduced metabolite TVX Q 5402 in human plasma is described. The method included a two-step solid-phase extraction on reversed-phase and cation-exchange material, followed by separation on a cyanopropyl silica gel column (5 microns; 250 mm x 4.6 mm I.D.). The eluent was 0.15 M acetate buffer (pH 4.7) containing 25% acetonitrile (w/w). Spiperone served as internal standard. The inclusion of the cation-exchange step provided sample purity higher than those achieved with other methods. After extraction of 1 ml of plasma, concentrations as low as 0.5 ng/ml were detectable for both benperidol and the metabolite. In plasma samples collected from a schizophrenic patient treated with a single oral dose of 6 mg of benperidol, plasma levels of benperidol and of the metabolite could be measured from 20 min to at least 12 h after administration.

Benperidol↗

[Not Available].

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Greece, Ancient↗