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O Benkert

Publications and source records attributed to O Benkert.

At least 37 records · Page 2Linked to original sources

Occupancy of striatal D(2)-like dopamine receptors after treatment with the sigma ligand EMD 57445, a putative atypical antipsychotic.

RATIONALE: EMD 57445 (panamesine) is a high affinity sigma ligand with the profile of an atypical antipsychotic in animal studies. It has been reported recently to have antipsychotic activity in schizophrenia. However, its metabolite, EMD 59983, binds also to D(2) and D(3) dopamine (DA) receptors. OBJECTIVES: The aim of this study was to test, using single photon emission computed tomography (SPECT) and [(123)I]iodobenzamide (IBZM) as the radiotracer, whether EMD 59983 would pass the blood-brain barrier and to what extent it would contribute to the effects of EMD 57445 in schizophrenia. METHODS: Two IBZM SPECT-scans were performed in five neuroleptic-free schizophrenic patients (DSM IV), one before and one after treatment with 60 mg panamesine daily for a treatment duration of 12-26 days. RESULTS: A high occupancy of striatal D(2)-like DA receptors similar to that induced by typical neuroleptics was observed in all patients treated with EMD 57445. CONCLUSIONS: Our results suggest that a possible antipsychotic activity of EMD 57445 in schizophrenia is not necessarily attributable to its affinity for sigma receptors, but could be simply due to the potent antidopaminergic effects of EMD 59983, its main metabolite.

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 METHODS: Blood was withdrawn at 15-min intervals to assess basal secretion of prolactin, growth hormone (GH), and thyroid-stimulating hormone (TSH).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↗

Psychological distress and psychiatric disorders in primary health care patients in East and West Germany 1 year after the fall of the Berlin Wall.

BACKGROUND: The reunification of Germany confronted citizens in East and West Germany with many changes in their lives. These changes may be considered as critical life events. Especially for those in East Germany, life circumstances drastically changed, and individuals were increasingly required to adopt and develop coping capabilities. In addition to new opportunities and freedom, there was threatening uncertainty about the future. Theories of life events and stress postulate that threat events have an impact on human well-being. It was expected that there would be an increased rate of psychiatric morbidity after unification, especially in the eastern part of Germany. METHOD: An international study by the WHO on psychiatric disorders in general health care was carried out in 1990, 1 year after the opening of the Berlin Wall, in both parts of Berlin and in Mainz, West Germany. This allowed for a comparison of the prevalence rates of psychiatric disorders among general health care patients in the East and West, after the euphoria immediately following unification had subsided. RESULTS: The prevalence rates of current ICD-10 diagnoses and of subthreshold disorders in East Berlin were similar to the rates in West Berlin and Mainz. The recognition rate of psychiatric disorders by physicians did not differ in East Berlin as compared to West Berlin and Mainz. CONCLUSION: Contrary to the prediction expected from the literature on individual negative life events, major changes in life circumstances and stressful life events on a societal level within 1 year did not have a major impact on psychological function.

Adult↗

The prescribing of psychotropic drugs by primary care physicians: an international collaborative study.

Psychotropic drugs play a major role in primary care management of mental disorders. This study expands the existing data on prescribing practices using data from a 15-center, primary care epidemiologic survey. Questions to be addressed include the following: Which clinical and nonclinical factors are related to the prescribing of psychotropic drugs by primary care physicians? How do prescribing patterns vary across primary care centers? At each center, primary care patients were screened using the General Health Questionnaire, and a stratified random sample completed a standardized diagnostic assessment. For each patient completing the diagnostic assessment, the treating primary care physician provided data on clinical diagnosis and medications prescribed. Study results indicated that 11.5% of all practice attenders, 51.7% of cases who received a diagnosis of mental disorders by a physician, and 27.6% of cases who received a diagnosis using the Composite International Diagnostic Interview were treated with psychotropic medication because of their psychologic problems. Anxiolytics, hypnotics, and antidepressants each accounted for approximately 20% of all prescriptions. Prescription rates increased with the prominence of psychologic complaints, severity of mental disorder, severity of social disability, female gender, age older than 40 years, lower education, unemployment, and marital separation. Rates and type of drugs also varied among specific mental disorders; 19.3% of patients with brief recurrent depression but 55.0% with agoraphobia got any psychotropic drug. Antidepressant drugs were prescribed in 7.7% of anxiety disorders compared with 31.9% of depressive disorders. There were large differences between international centers. When comparing client-type centers with clinic-type centers, overall prescription rates were similar (51.2 vs. 52.9%), but significant differences were observed with respect to psychotropic polypharmacy (12.6% client, 6.3% clinic), tranquilizer medication (24.2 client, 32.9% clinic), and antidepressant medication (17.3 client, 8.9% clinic). Psychotropic drugs have an important role in the treatment of mental disorders by general practitioners. Prescription is associated with a number of clinical but also nonclinical factors that must be recognized when guidelines for international use are to be published. Recognition of mental disorders and selection of specific drug classes are important areas in which medical practice needs improvement.

Adult↗

Randomised placebo-controlled trial of moclobemide, cognitive-behavioural therapy and their combination in panic disorder with agoraphobia.

BACKGROUND: In the treatment of panic disorder with agoraphobia, the efficacy of pharmacological, psychological and combined treatments has been established. Unanswered questions concern the relative efficacy of such treatments. AIMS: To demonstrate that moclobemide and cognitive-behavioural therapy (CBT) are effective singly and more effective in combination. METHOD: Fifty-five patients were randomly assigned to an eight-week treatment of: moclobemide plus CBT; moclobemide plus clinical management ('psychological placebo'); placebo plus CBT; or placebo plus clinical management. RESULTS: Comparisons between treatments revealed strong effects for CBT. Moclobemide with clinical management was not superior to placebo. The combination of moclobemide with CBT did not yield significantly better short-term results than CBI with placebo. The CBT results remained stable during a six-month follow-up, although a substantial proportion of patients treated with placebo plus CBT needed additional treatment. CONCLUSIONS: CBT was highly effective in the treatment of panic disorder with agoraphobia and reduced agoraphobia to levels that were comparable to those of non-clinical controls.

Adolescent↗

[Dementia screening in routine clinical practice. A comparative analysis of MMSE, SIDAM and ADAS].

Dementia-screening in clinical routine requires short, sensitive and specific tools. A number of standardized instruments are available for this purpose. The present study analysed the relationship between size of three exemplary dementia-screening tests and their diagnostic accuracy. The Mini-Mental-State-Examination (MMSE), the Structured Interview for the Diagnosis of Dementia of the Alzheimer-type, Multiinfarct Dementia and Dementias of other Aetiologies according to ICD-10 and DSM-III-R (SIDAM) and the Alzheimer's Disease Assessment Scale (ADAS) were applied to 71 patients with dementia of the Alzheimer-type and 73 non-demented controls. A ROC-analysis revealed that neither SIDAM nor ADAS differentiated better between demented and non-demented probands than the MMSE. This was also true for patients with mild dementia. In dementia staging the more comprehensive instruments did not surpass the MMSE, too. Due to it's brevity, the MMSE is the preferential screening-instrument for clinical routine.

Aged↗

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↗

Conventional and spectral power analysis of all-night sleep EEG after subchronic treatment with paroxetine in healthy male volunteers.

Paroxetine is a selective and potent serotonin reuptake inhibitor with reported antidepressant properties. Since changes in the regular sleeping pattern were described as side effects under treatment with paroxetine, the impact of the drug on the sleep architecture is of major interest. The present study addressed the question of subchronic effects of paroxetine medication (30 mg/day) in eight healthy male volunteers in a double blind, placebo-controlled crossover-design. Conventional sleep EEG parameters and additionally computed spectral power analysis based on FFT of 20-s time epochs in the delta, theta, alpha, beta and gamma frequency range for different sleep stages after 4 weeks of treatment were investigated. Subchronic paroxetine administration in healthy subjects led to a prolonged REM latency and a decrease in the number of REM phases, whereas sleep efficiency, total sleep time, sleep onset latency, number of awakenings, and awake during sleep period time were not altered by paroxetine medication. Moreover, we could not detect any alterations of the spectral power values in certain frequency bands during NREM or REM sleep following subchronic paroxetine medication.

Adult↗

Fluvoxamine or placebo in the treatment of panic disorder and relationship to blood concentrations of fluvoxamine.

A six-week double-blind placebo-controlled trial of fluvoxamine was undertaken in 46 patients suffering from panic disorder with or without agoraphobia diagnosed by DSM-III-R guidelines. Average daily dosage of fluvoxamine was 160 mg, with a highest permitted dose of 300 mg/day. Weekly evaluation included a diary in which the number, severity, and duration of full-blown and limited panic attacks and the duration and severity of anticipating fear, CAS, GAS, CGI, HAM-D, adverse effects and the number of capsules not taken were noted. Fluvoxamine was not significantly superior to placebo with regard to the main outcome criterion, i.e., the reduction in the number of panic attacks, but it was significantly more effective with regard to the diminution in the number of limited panic attacks and showed a tendency to significance in respect of GAS and CGI. Plasma levels of fluvoxamine were measured at the end of week one and at the end of the study. Most patients with complete remission at the end of the study were found in the verum group with plasma fluvoxamine levels ranging from 10 to 100ng/ml. It is suggested that therapeutic response might be maximized by monitoring fluvoxamine concentrations in blood.

Adolescent↗

[Psychopharmacotherapy in pregnancy and breast feeding].

The primary purpose of this article is to review critically the literature on the use of psychotropic medications in pregnancy and during breast feeding in order to suggest strategies for the clinical management of these periods. Use of psychotropic medications during pregnancy may cause three complications: 1. teratogenicity, 2. perinatal syndromes (neonatal toxicity), and 3. postnatal behavioural sequelae (behavioural toxicity). The literature features few well-controlled studies concerning these points, so that the available information allows only few conclusions. Exposure to certain psychotropic drugs in utero may increase the risk for some specific congenital anomalies; there is mostly no strong evidence for behavioural toxicity in children exposed to psychotropic medications. Use of psychotropic drugs during pregnancy and breast feeding may be appropriate in many clinical situations and should include thoughtful weighing of risk of pre- and postnatal exposure versus risk of relapse following drug discontinuation. The authors try to present disorder-based guidelines for psychotropic drug use during pregnancy and breast feeding and for psychiatrically ill women who wish to conceive.

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↗

Improvement of picture recall by repetition in patients with dementia of Alzheimer type.

The evidence for positive effects of repetition on recall performance in patients with dementia of Alzheimer type is equivocal. This may be due to the difference repetition conditions used. The aim of this study was therefore to evaluate the effects of different repetition modes on the improvement of recall performance in demented subjects. Twenty-four patients with Alzheimer type dementia and 24 control subjects with remitted depression were included in the study. Pictures were presented repeatedly using different presentation modes at a constant total presentation time. Free recall was tested repeatedly after different periods of delay (0-8 hours). Immediate and delayed list repetition significantly improved recall performance in both groups. Within-list repetition did not improve total recall in demented subjects. The repeated measurement design sensitively detected minor changes in recall performance. These were not observed using other measures of recall and recognition (hits, false alarms, indices of signal discrimination).

Aged↗

Analysis of sleep EEG microstructure in subchronic paroxetine treatment of healthy subjects.

Paroxetine is a selective and potent serotonin reuptake inhibitor and its efficacy for the treatment of depression has been proven. Under acute and subchronical treatment regimens, disturbances of the regular sleep pattern are a reported side effect of the drug. The present study was therefore performed to investigate the impact of subchronic treatment with the selective serotonin reuptake inhibitor paroxetine on the microstructure of the sleep EEG. The study especially addressed the question of subchronic effects of paroxetine medication (30 mg/day) in eight healthy male volunteers in a double blind, placebo-controlled crossover design. Conventional sleep EEG parameters and a spectral power analysis for different sleep stages after 4 weeks of treatment were computed. Additionally, the correlation of certain EEG rhythms across the night was calculated in order to detect subtle dynamical EEG alterations, not necessarily obvious when regarding conventional EEG analysis. Although we could not detect any alterations of the spectral power values in certain frequency bands either during NREM nor during REM sleep following subchronic paroxetine medication, the dynamical EEG attributes across the night revealed a significant enhancement of the correlation between certain EEG rhythms mainly during NREM sleep.

Adult↗

Response to treatment in minor and major depression: results of a double-blind comparative study with paroxetine and maprotiline.

Several concepts of minor depression in the sense of acute but less severe symptomatology than major depression have been proposed in the literature, but currently none of them is generally accepted. For the treatment of these conditions, only few recommendations based on empirical data are available. We conducted a randomized double-blind multicentre study in depressed outpatients comparing paroxetine and maprotiline in both patients with minor (n = 245) and major depression (n = 298). For the diagnosis, Research Diagnostic Criteria were used in a modified version. Two response criteria were applied: a reduction of 50% or more in total HAMD-17 scores from baseline (criterion 1), and a reduction of the HAMD-17 total score to 9 points or less (criterion 2). A completer and an endpoint analysis was performed. For patients with minor depression, remarkably high response rates were found for paroxetine (criterion 1: 90.9% completer, 82.1% endpoint; criterion 2: 89.1% completer, 82.4% endpoint) while the respective rates for maprotiline tended to be lower (criterion 1: 80.4% completer, 71.4% endpoint; criterion 2: 84.9% completer; 76.1% endpoint). Response rates in patients with major depression were for paroxetine: criterion 1: 74.3% completer, 62.8% endpoint; criterion 2: 76.4% completer, 65.2% endpoint; and for maprotiline: criterion 1:82.4% completer, 68.5% endpoint; criterion 2: 80.6% completer; 66.0% endpoint, which resembles rates reported from previous antidepressant trials. Both drugs were generally well tolerated. Though no placebo control was carried out, our results suggest that minor depression is a disorder that is very likely to respond to antidepressant pharmacotherapy with paroxetine, but also with maprotiline at a favourable risk/benefit ratio.

Adolescent↗

A double-blind study comparing paroxetine and maprotiline in depressed outpatients.

A double-blind multicenter randomized parallel group study comparing paroxetine and maprotiline was carried out in a total of 544 outpatients. Included were patients with varying degrees of severity of depressive symptoms who fulfilled modified RDC criteria for either Minor or Major Depression and showed a HAMD-17 score of > or = 13. No concomitant benzodiazepine treatment was allowed. Duration of treatment was 6 weeks, after an initial wash-out period. Doses were fixed during the first 3 weeks of treatment, patients receiving either 20 mg paroxetine or 100 mg maprotiline daily. An option for dose escalation was provided for insufficient responders after 3 weeks. The weekly assessments comprised rating of the HAMD-17, MADRS, BRMS, RDS, HAMA, CAS, and CGI scales and registration of adverse events by non-leading questions. An intention-to-treat and a completer analysis were performed. Response was defined as a HAMD-17 reduction of > or = 50% or a HAMD-17 score of < or = 9 at the end of the study or at dropout. The treatment groups were comparable according to demographic data. Overall evaluation indicated equieffective and good antidepressant and anxiety-reducing properties for paroxetine and maprotiline. No persistent significant differences between treatment groups were observed on any assessment instrument. There was no difference in the frequency of observed side-effects, but side-effect profiles were markedly different, as maprotiline patients had more anticholinergic and paroxetine patients more SSRI-typical side-effects.

Adult↗

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↗

Dose escalation vs. continued doses of paroxetine and maprotiline: a prospective study in depressed out-patients with inadequate treatment response.

In view of the fact that controlled prospective studies on the benefits of dose escalation of the selective serotonin re-uptake inhibitor (SSRI) paroxetine are lacking, we conducted a double-blind, randomized, parallel-group multicentre study designed to compare the possible benefits of dose escalation of paroxetine and maprotiline in patients suffering from major or minor depression according to modified Research Diagnostic Criteria (RDC) with inadequate treatment response. The study sample consisted of 544 out-patients with different degrees of severity of depression. Patients received either 20 mg paroxetine (n = 271) or 100 mg maprotiline (n = 273) for the first 3 weeks in a double-blind manner. Response after 3 weeks was defined using explicit operationalized criteria. Patients with inadequate treatment response (paroxetine group, n = 86; maprotiline group, n = 88) were again randomized to either continuation of the previous dosage (paroxetine, n = 36; maprotiline, n = 48) or increased doses, i.e. 40 mg paroxetine (n = 50) or 150 mg maprotiline (n = 40), respectively. Intention-to-treat and completer analyses were performed. Defining response as a reduction in Hamilton Depression Rating Scale (17-item version) (HAMD-17) score of at least 50% from baseline, no significant benefits of dose escalation were found for either paroxetine or maprotiline. Stratification according to baseline severity of depression also revealed no significant benefits of dose escalation. After dose escalation, new adverse events that had not been present during treatment with lower doses rarely occurred. Our results support the view that a dose of 20 mg paroxetine is optimal for the acute treatment of depression in the majority of patients.

Adult↗