Biomedical subjects

Eckart Rüther

Publications and source records attributed to Eckart Rüther.

At least 19 recordsLinked to original sources

PubMed2007

The quantification inventory for somatoform syndromes (QUISS): a novel instrument for the assessment of severity.

BACKGROUND: To date, specific scales for the assessment of severity of somatoform disorders are still rare. Characteristic cognitive and behavioural domains, representing severity are not incorporated in the existing scales. Results with the novel quantification inventory for somatoform syndromes (QUISS) are presented in this paper. METHODS: The QUISS has been developed as a qualified severity scale for patients fulfilling diagnostic criteria according to DSM-IV or/and ICD-10. It was designed to be particularly suitable for application in clinical trials and for monitoring the efficacy of psychotherapy and pharmacotherapy. Not only number, severity and frequency of somatoform symptoms, but also common cognitive and behavioural domains of somatoform disorders have been included into this instrument. Both an 18-item patient- and observer-rated version are available taking about 20 min to complete. The questionnaire was applied to patients with somatoform disorder (N = 96), major depression (N = 24), and panic disorder (N = 16). RESULTS: The psychometric properties of the scale are satisfactory. The QUISS showed high objectivity (Cronbach's alpha = 0.90 for both versions; inter-scale correlations r = 0.64-0.88; p < 0.05), good test-retest- (r = 0.87; p < 0.05) and inter-rater-reliability (r = 0.89; p < 0.05). External validity (moderately high correlations of QUISS-T to SOMS 7T (r = 0.54), significant discrimination to major depression p < 0.05) was satisfactory. Factor structure revealed five relevant factors. CONCLUSIONS: The QUISS could be a useful instrument in somatoform disorders for the assessment of syndrome severity and treatment outcome in scientific and clinical settings.

Activities of Daily Living↗

PubMed2007

Psychopathological characteristics and treatment response of first episode compared with multiple episode schizophrenic disorders.

OBJECTIVE: The aim was to investigate the hypothesis that patients with first episode schizophrenic disorders have a more favorable treatment response than those with multiple episodes. METHOD: A total of 400 inpatients from an ongoing multi-centre, follow-up program who fulfilled ICD-10 criteria for schizophrenic disorders (F2) were assessed at admission to and discharge from hospital using the Positive and Negative Syndrome Scale (PANSS). RESULTS: At admission, first episode patients (n = 121) showed higher levels of positive symptoms (PANSS positive subscore) and lower ones of negative symptoms (PANSS negative subscore) than multiple episode patients (n = 279), whereas the global disease severity (PANSS total score) was comparable. Analyses of covariance revealed that treatment response (adjusted symptom levels at discharge) was more favorable in first-episode patients, with respect to both positive and negative symptoms. CONCLUSION: The results are compatible with the hypothesis that treatment response becomes less favorable during the course of schizophrenic illness. This finding might be associated with progressive neurobiological alterations.

Adult↗

PubMed2006

Effect of chronic citalopram on serotonin-related and stress-regulated genes in the dorsal raphe nucleus of the rat.

Using a model of depression in which chronic social stress induces depressive-like symptoms, we investigated effects of the selective serotonin-reuptake inhibitor (SSRI) citalopram on gene expression in the dorsal raphe nucleus of male rats. Expression of tryptophan hydroxylase (TPH) protein was found to be upregulated by the stress and normalized by citalopram, while mRNAs for genes TPH 1 and 2 were differentially affected. Citalopram had no effect on serotonin transporter mRNA but reduced serotonin-1A autoreceptor mRNA in stressed animals. The SSRI prevented the stress-induced upregulation of mRNA for CREB binding protein, synaptic vesicle glycoprotein 2b and the glial N-myc downstream-regulated gene 2, but increased mRNA for neuron-specific enolase (NSE) in both stressed and unstressed animals having no effect on stress-induced upregulation of NSE protein. These findings demonstrate that in the dorsal raphe nucleus of chronically stressed rats, citalopram normalizes TPH expression and blocks stress effects on distinct genes related to neurotransmitter release and neuroplasticity.

Animals↗

PubMed2006

The efficacy of the dopamine D2/D3 antagonist tiapride in maintaining abstinence: a randomized, double-blind, placebo-controlled trial in 299 alcohol-dependent patients.

In this investigation, the hypothesis was tested whether the selective dopamine D2/D3 receptor antagonist tiapride is effective in maintaining abstinence after detoxification in alcohol-dependent patients. The rationale of the study was based on the relevance of the dopaminergic system for addictive behaviour as well as some preliminary studies. A multi-centre, randomized, double-blind, placebo-controlled, parallel-group study was conducted. A total of 299 detoxified alcohol-dependent patients (ICD-10: F10.2) received either tiapride (300 mg/d) or placebo over a 24-wk study period. Subjects with severe comorbid psychiatric disorder such as schizophrenia or Wernicke-Korsakoff syndrome were excluded. Primary outcome variable was the time to first relapse with relapse defined as any alcohol consumption after detoxification. Data analysis was done with Kaplan-Meier estimates with log-rank test (one-sided, p<0.05). Tiapride was not superior to placebo in maintaining abstinence. The time to first relapse was 71 d in the tiapride group and 92 d in the placebo group (log-rank test, p=0.9895). Relapse rate was higher in the intervention group (54.4%) than in the control group (40.7%). Like the dopamine antagonist flupenthixol, tiapride was not effective in maintaining alcohol abstinence. Regarding the high success rate in the placebo group the influence of psychosocial treatment in studies investigating drug effects on the course of alcohol dependence has to be considered.

Adult↗

PubMed2006

Identification of genes regulated by chronic social stress in the rat dorsal raphe nucleus.

1. Changes in the serotonergic (5-HT) system are suspected to play a role in stress-induced neuropathologies and neurochemical measures indicate that serotonergic neurons in the dorsal raphe nucleus (DRN) are activated during stress. In the present study we analyzed gene expression in the DRN after chronic social stress using subtractive cDNA hybridization. 2. In the resident intruder paradigm, male Wistar rats were chronically stressed by daily social defeat during 5 weeks, RNA was isolated from their DRN, cDNA was generated, and subtractive hybridization was performed to clone sequences that are differentially expressed in the stressed animals. 3. From the cDNA libraries that were obtained, we selected the following genes for quantitative Real-time PCR: Two genes related to neurotransmission (synaptosomal associated protein 25 and synaptic vesicle glycoprotein 2b), a glial gene presumptively supporting neuroplasticity (N-myc downstream-regulated gene 2), and a gene possibly related to stress-induced regulation of transcription (CREB binding protein). These four genes were upregulated after the chronic social stress. Quantitative Western blotting revealed increased expression of synaptosomal associated protein 25 and synaptic vesicle glycoprotein 2b. 4. Genes directly related to 5-HT neurotransmission were not contained in the cDNA libraries and quantitative Real-time PCR for the serotonin transporter, tryptophan hydroxylase 2 and the 5-HT(1A) autoreceptor confirmed that these genes are not differentially expressed after 5-weeks of daily social stress. 5. These data show that 5 weeks of daily social defeat lead to significant changes in expression of genes related to neurotransmission and neuroplasticity in the DRN, whereas expression of genes directly related to 5-HT neurotransmission is apparently normal after this period of chronic stress.

Adrenal Glands↗

PubMed2006

CSF amyloid-beta-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia.

As the differential diagnosis of dementias based on established clinical criteria is often difficult, biomarkers for applicable diagnostic testing are currently under intensive investigation. Amyloid plaques deposited in the brain of patients suffering from Alzheimer's disease, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) mainly consist of carboxy-terminally elongated forms of amyloid-beta (Abeta) peptides, such as Abeta1-42. Absolute Abeta1-42 levels in CSF have shown diagnostic value for the diagnosis of Alzheimer's disease, but the discrimination among Alzheimer's disease, DLB and PDD was poor. A recently established quantitative urea-based Abeta-sodium-dodecylsulphate-polyacrylamide-gel-electrophoresis with Western immunoblot (Abeta-SDS-PAGE/immunoblot) revealed a highly conserved Abeta peptide pattern of the carboxy-terminally truncated Abeta peptides 1-37, 1-38, 1-39 in addition to 1-40 and 1-42 in human CSF. We used the Abeta-SDS-PAGE/immunoblot to investigate the CSF of 23 patients with Alzheimer's disease, 21 with DLB, 21 with PDD and 23 non-demented disease controls (NDC) for disease-specific alterations of the Abeta peptide patterns in its absolute and relative quantities. The diagnostic groups were matched for age and severity of dementia. The present study is the first attempt to evaluate the meaning of Abeta peptide patterns in CSF for differential diagnosis of the three neurodegenerative diseases--Alzheimer's disease, DLB and PDD. The Abeta peptide patterns displayed disease-specific variations and the ratio of the differentially altered Abeta1-42 to the Abeta1-37 levels subsequently discriminated all diagnostic groups from each other at a highly significant level, except DLB from PDD. Additionally, a novel peptide with Abeta-like immunoreactivity was observed constantly in the CSF of all 88 investigated patients. The pronounced percentage increase of this peptide in DLB allowed a highly significant discrimination from PDD. Using a cut-off point of 0.954%, this marker yielded a diagnostic sensitivity and specificity of 81 and 71%, respectively. From several lines of indication, we consider this peptide to represent an oxidized alpha-helical form of Abeta1-40 (Abeta1-40*). The increased abundance of Abeta1-40* probably reflects a disease-specific alteration of the Abeta1-40 metabolism in DLB. We conclude that Abeta peptide patterns reflect disease-specific pathophysiological pathways of different dementia syndromes as distinct neurochemical phenotypes. Although Abeta peptide patterns failed to fulfil the requirements for a sole biomarker, their combined evaluation with other biomarkers is promising in neurochemical dementia diagnosis. It is noteworthy that DLB and PDD exhibit distinct clinical temporal courses, despite their similar neuropathological appearance. Their distinct molecular phenotypes support the view of different pathophysiological pathways for each of these neurodegenerative diseases.

Aged↗

PubMed2006

Panic disorder during pregnancy and postpartum period.

BACKGROUND: Earlier studies on the influence of pregnancy and postpartum period on the course of panic disorder have been inconsistent. The present study aims to quantify panic manifestations in these periods in large sample of women. METHOD: Panic manifestations, including exacerbations and new manifestations of panic disorder, were assessed retrospectively in a sample of 128 women with panic disorder with or without agoraphobia, 93 of whom had had 195 pregnancies. RESULTS: Panic manifestations were fewer during pregnancy and more frequent in the postpartum period when compared with the control period. Women who had never been pregnant had significantly more panic manifestations than women with prior pregnancies. Breastfeeding and miscarriages did not have a significant effect. Women with postpartum panic reported more psychosocial stress events during this period. CONCLUSIONS: Possible reasons for postpartum panic and the protective effects of pregnancy are discussed, including psychosocial or hormonal factors and other neurobiological changes. Postpartum panic coincides with a sudden drop of hormones after delivery.

Adult↗

PubMed2006

The atypical antipsychotics olanzapine and quetiapine, but not haloperidol, reduce ACTH and cortisol secretion in healthy subjects.

RATIONALE: Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis is an important aspect of the pathophysiology of major depression and schizophrenia. Despite the usefulness of atypical antipsychotics in the treatment of depression and their positive influence on cognitive functioning possibly related to their impact on cortisol, little is known about their effect on HPA axis function. OBJECTIVE: Therefore, this double-blind, placebo-controlled, randomized cross-over study investigated the influence of the atypical antipsychotics quetiapine and olanzapine in comparison with haloperidol and placebo on plasma adrenocorticotropic hormone (ACTH), cortisol, and prolactin levels. Eleven healthy male volunteers were studied during four sessions one week apart, orally receiving placebo, quetiapine (50 mg), olanzapine (5 mg), or haloperidol (3 mg). Blood samples were taken at hourly intervals from 0900 until 1700 hours. For ACTH, cortisol, and prolactin a significant effect of treatment condition (p < or = 0.005; p < or = 0.035; p < or = 0.0001, respectively) for area under the curve (AUC) was found. In comparison to placebo, quetiapine and olanzapine significantly reduced ACTH (p < or = 0.002; p < or = 0.05, respectively) and cortisol (p < or = 0.005; p < or = 0.03, respectively). No effect of haloperidol on AUC of ACTH or cortisol levels was observed. In comparison with placebo, haloperidol (p < or = 0.0001) and olanzapine (p < or = 0.0001) elevated AUC of prolactin plasma levels, whereas no significant effect was observed for quetiapine as a main effect of treatment condition. The atypical antipsychotics' strong influence on HPA-function with pronounced ACTH and cortisol lowering is possibly related to the atypicals' blockade of serotonergic receptors, but blockade of adrenergic or histaminergic receptors may play a role as well. The observed HPA-axis down-regulation may be clinically important for the atypicals' effects on depressive symptomatology and cognitive functioning.

Adrenocorticotropic Hormone↗

PubMed2006

A decision model to compare health care costs of olanzapine and risperidone treatment for schizophrenia in Germany.

Second-generation atypical antipsychotics such as clozapine, olanzapine, risperidone, quetiapine, ziprasidone, amisulpride and ariprazole offer the potential to reduce the significant health care resource demands in the treatment of schizophrenia through improved levels of initial clinical response and reduced levels of long-term acute relapse. However, the optimal sequencing of these drugs remains unclear. To consider this issue from a health economic viewpoint a decision model approach was used comparing healthcare costs and clinical outcomes when treating patients with alternative sequences of atypical antipsychotic treatment. Treated patients were assumed to be in a current acute episode with at least a 10-year history of disease and to be naive to previous atypical treatments. Treatment strategies were based on either first-line olanzapine or risperidone with switching to the alternative drug as second-line treatment following an inadequate clinical response to first-line drug therapy. Clinical response data were derived from a pivotal published comparative study of both olanzapine and risperidone. Published data on the long-term use of antipsychotic drugs where used wherever possible to populate the model for relapse rates during the maintenance phase. Health care resource data were defined for Germany based on expert clinical opinion. A treatment strategy of first-line olanzapine was shown to be cost saving over a 1-year period, with additional clinical benefits in the form of avoided relapses. The model suggests that over the first year of treatment a strategy of first-line olanzapine is associated with lower risk of additional relapse (0.33 fewer acute relapses per 100 patients per year) and with cost savings (euro 35,306 per 100 patients per year). There is a need for longer term direct in-trial comparisons of atypical antipsychotics to confirm these indicative results.

Antipsychotic Agents↗

PubMed2006

Citalopram counteracts depressive-like symptoms evoked by chronic social stress in rats.

Recently, we have described a new model of chronic social stress in rats, based on the resident-intruder paradigm. In this model, rats show behavioural changes that may be considered correlates of depressive symptoms, such as anhedonia and motivational deficits. The present study was designed for pharmacological validation of this model. Animals were socially stressed for 5 weeks and, in parallel, after the first week of stress, they were subjected to chronic (4 weeks) treatment with the antidepressant drug citalopram. The drug was administered via drinking water (30 mg/kg). The optimal dose of citalopram was determined in a pilot study. After 4 weeks of treatment, plasma levels of citalopram and its metabolite were found to be within the human therapeutic range. The effects of social stress and citalopram treatment were assessed by behavioural tests. Chronically stressed rats showed reduced locomotor and exploratory activity, reduced sucrose preference and increased immobility time in the forced swimming test. Chronic oral administration of citalopram abolished those effects and normalized behaviours related to motivation and reward sensitivity. These observations provide evidence for the predictive validity of the chronic social stress paradigm as a model of depressive symptoms in rats.

Administration, Oral↗

PubMed2006

Follow-up of 180 alcoholic patients for up to 7 years after outpatient treatment: impact of alcohol deterrents on outcome.

OBJECTIVE: (1) To perform a 9-year study of abstinence, lapse, and relapse in 180 chronic alcoholic patients, participants of the Outpatient Longterm Intensive Therapy for Alcoholics (OLITA); (2) To investigate the role of supervised alcohol deterrents (AD) in relapse prevention and as an adjunct for maintenance of long-term abstinence. METHOD: This prospective open treatment study evaluates the long-term course of drinking outcomes and AD use of 180 chronic alcoholics consecutively admitted from 1993 to 2002. Subsamples are compared for (1) sham-AD versus verum-AD (disulfiram/calcium carbimide), (2) coped lapses versus finally detrimental lapses versus malignant relapses, and (3) AD use for 13 to 20 versus >20 months. RESULTS: In this 9-year study, the cumulative probability of not having relapsed was 0.52, and that of not having consumed any alcohol was 0.26. Despite long-term use, disulfiram/calcium carbimide was well tolerated. Patients on sham-AD (due to contraindications to verum-AD) showed higher cumulative abstinence probability than patients on verum (S = 0.86 vs. S = 0.49, p = 0.03). Detrimental lapses and malignant relapses occurred earlier than successfully coped lapses (p < 0.001); patients with detrimental lapse and with malignant relapse had fewer days of AD intake and less subsequent days without AD than patients with coped lapse (p < 0.001). The cumulative abstinence probability was S = 0.75 for patients with long-term intake compared with S = 0.50 for patients who stopped AD between months 13 and 20 (p < 0.001). CONCLUSIONS: An abstinence rate of >50% in this 9-year study strongly supports the concept of comprehensive, long-term outpatient treatment of alcoholics. Supervised, guided intake of AD, also over extended periods, can be used as a predominantly psychologically acting ingredient of successful alcoholism therapy.

Adult↗

PubMed2005

Memantine inhibits ethanol-induced NMDA receptor up-regulation in rat hippocampal neurons.

The present study examined the effect of memantine, an uncompetitive NMDA receptor antagonist, on ethanol-induced NMDA receptor up-regulation. Primary glutamatergic rat hippocampal neurons were exposed to ethanol and memantine for 5 days. The ethanol-sensitive NMDA receptor subunits NR1, NR2A and NR2B were quantified by Western immunoblot analysis. Exposure to ethanol (50 mM) caused an increase in the levels of NR1 (137 +/- 11% of untreated control, P = 0.009), NR2A (128 +/- 14%, P = 0.022) and NR2B (136 +/- 19%, P = 0.012). Coincubation with memantine (10 microM) completely blocked the ethanol-induced up-regulation of NR1 (102 +/- 4%), NR2A (95 +/- 7%) and NR2B (105 +/- 13%). No effect of memantine on NR subunit expression was observable, except for NR2A, where a decrease (79 +/- 6%, P = 0.034) was noted. Neither ethanol nor memantine alone or in combination were toxic in the concentrations tested. These results may provide a molecular explanation for beneficial effects of memantine on ethanol-induced glutamatergic hyperexcitability reflected in the ethanol withdrawal syndrome and on the development of ethanol dependence.

Analysis of Variance↗

PubMed2005

Narcolepsy increased L-PGDS (beta-trace) levels correlate with excessive daytime sleepiness but not with cataplexy.

OBJECTIVES: Alterations in the prostaglandin-D-system have been found in animal sleep experiments and disorders that present with hypersomnia or sleep disturbances. The recently demonstrated involvement of the leptomeningeal lipocalin-type prostaglandin-Dsynthase (L-PGDS) (beta-trace) in human physiological sleep encouraged us to investigate its role in the pathophysiology of narcolepsy. METHODS: In a pilot study, serum LPGDS and melatonin concentrations were assessed in 14 narcoleptic patients during undisturbed sleep and total sleep deprivation, compared with those from 14 healthy controls during undisturbed sleep. Excessive daytime sleepiness was measured by a standardized questionnaire (Epworth sleepiness scale, ESS). RESULTS: In narcoleptic patients, markedly increased baseline L-PGDS levels were significantly correlated with the ESS score, but not with the degree of cataplexy. Serum L-PGDS concentrations in patients as well as in controls followed a time-dependent fluctuation with evening increases, highest values during the night and in the morning. Compared with controls, patients exhibited significant/increased amplitude of circulating L-PGDS without any suppression by total sleep deprivation. CONCLUSION: These findings indicate that the prostaglandin-D-system contributes to the pathophysiology of narcolepsy, e. g. the regulation of excessive daytime sleepiness. Since it has been suggested that L-PGDS is also involved in neurodegenerative disorders, there may be a more specific role of the prostaglandin- D-system in narcoleptic aetiogenesis. Moreover, its linkage with the immune system as well as with human sleep regulation offers a direct access for investigating both systems.

Adolescent↗

PubMed2005

Early traumatic life events, parental attitudes, family history, and birth risk factors in patients with borderline personality disorder and healthy controls.

Patients with borderline personality disorder (BPD) were compared with a healthy control group with regard to traumatic life events during childhood. The patients (n=66) and controls (n=109) were investigated using a comprehensive retrospective interview with 203 questions about childhood traumatic life events, parental attitudes, family history of psychiatric disorders and birth risk factors. The frequency of reports of traumatic childhood experiences was significantly higher in patients than in controls, including sexual abuse, violence, separation from parents, childhood illness, and other factors. On a 0- to 10-point "severe trauma scale," patients had significantly more severe traumatic events (mean score=3.86, SD=1.77) than control subjects (0.61, SD=0.93). Only four (6.1%) of the BPD patients, but 67 (61.5%) of the controls did not report any severe traumatic events at all. Compared with controls, patients described the attitude of their parents as significantly more unfavorable in all aspects. Patients reported significantly higher rates of psychiatric disorders in their families in general, especially anxiety disorders, depression, and suicidality. Among birth risk factors, premature birth was reported more often in BPD subjects. In a logistic regression model of all possible etiological factors examined, the following factors showed a significant influence: familial neurotic spectrum disorders, childhood sexual abuse, separation from parents and unfavorable parental rearing styles. The present data support the hypothesis that the etiology of BPD is multifactorial and that familial psychiatric disorders and sexual abuse are contributing factors.

Adolescent↗

PubMed2005

Anhedonia and motivational deficits in rats: impact of chronic social stress.

Stress, especially chronic stress, is one of the most important factors responsible for precipitation of affective disorders in humans. The animal models commonly used in the investigation of stress effects are based mainly on powerful physical stressors. In the majority of cases, these models are not relevant to situations that human beings encounter in everyday life. In our study, an animal model for chronic social stress has been developed for rats using a resident-intruder paradigm. This paradigm is considered a model of social defeat or subordination, and therefore may mimic situations occurring in humans. Rats were subjected daily to subordination stress for a period of five weeks and, in parallel, tested with a battery of behavioural tests. Chronically stressed rats showed behavioural changes, including decreased motility and exploratory activity, increased immobility in a forced swim test, and reduced preference for sweet sucrose solution (anhedonia). Reduced locomotor and exploratory activity represents a loss of interest in new stimulating situations, implying a deficit in motivation. Increased immobility in the forced swim test indicates behavioural despair, a characteristic of depressive disorders. Decreased sucrose preference may indicate desensitisation of the brain reward mechanism. Since anhedonia is one of the core symptoms of depression in humans, our findings suggest that the rat chronic social stress model may be an appropriate model for depressive disorders.

Adrenal Glands↗

PubMed2005

Obstructive sleep apnea: Plasma endothelin-1 precursor but not endothelin-1 levels are elevated and decline with nasal continuous positive airway pressure.

Assessment of plasma endothelin-1 (ET-1) reveals conflicting results in cerebral and noncerebral conditions. Obstructive sleep apnea (OSA) syndrome has been used as a definite challenge for the investigation of endothelin measurements. Despite marked sleep-related breathing disturbances in untreated patients peripherally measurable ET-1 concentrations remained within the normal range and did not change after an appropriate therapy with continuous positive airway pressure (CPAP). In contrast, its precursor, big ET-1, was considerably elevated in untreated patients and dropped to normal values after long-term CPAP depending on compliance. Relatively stable big ET-1 elevations in untreated patients, during sleep and wakefulness, suggest that a general endothelial alteration beyond that explained by a direct impact of nocturnal breathing disturbances on the vascular system occurs. CPAP-therapy effectively lowered plasma big ET-1 in compliant patients and thus possibly their related risk for vascular diseases. Big ET-1 has been demonstrated to be a more appropriate marker of endothelial alteration than ET-1 because of its longer half-life. Simultaneous measurements are to be recommended.

Adult↗

PubMed2005

[Motor disturbances in psychiatric patients].

Motor disturbances are common symptoms in schizophrenia. They can be caused by the illness itself or by antipsychotic treatment. The author gives an overview of the history of research in this topic and discusses the relationship of motor disturbances with many other aspects of psychopathology and subjective well-being of the patients, such as cognitive, emotional and social functioning.

Basal Ganglia Diseases↗

PubMed2005

Risperidone: an open-label, observational study of the efficacy, tolerability, and prescribing behavior in acutely exacerbated patients with schizophrenia.

OBJECTIVE: Efficacy of atypical antipsychotic in acute schizophrenic episodes is still in debate. This study evaluated treatment practices over 7 years of initial treatment with oral risperidone in acutely exacerbated patients with schizophrenia and in a subgroup of highly agitated, tense, and aggressive patients. Additionally, the study investigated the efficacy and tolerability of risperidone in routine clinical practice. METHODS: In a prospective, multicenter, observational trial from 1996 to 2002, patients with schizophrenia experiencing acute symptom exacerbations were treated with risperidone within 24 hours of inpatient admission. Patients with a total score of > or =15 points on the agitation subscale of the Positive and Negative Syndrome Scale (PANSS) were defined as highly agitated. Efficacy measures were carried out with a modified PANSS, the Clinical Global Impression (CGI) and the Brief Psychiatric Rating Scale (BPRS). RESULTS: A total of 1625 patients were evaluated. Despite prescription of decreasing risperidone dosages over 7 years, efficacy was maintained and tolerability improved significantly. Significant symptom relief occurred in all patients and was more pronounced in the subgroup of highly agitated patients (n = 256; P < 0.001 for PANSS, BPRS, and CGI). At Week 6, the mean daily dosage of risperidone was 4.8 mg in the highly agitated patients and 4.7 mg in the remaining patients, and more than 55% of all patients were receiving risperidone as monotherapy. CONCLUSIONS: Prescribing patterns with risperidone in patients with acutely exacerbated schizophrenia, including highly agitated patients, changed with the experience gained with this compound. In routine clinical practice in this indication, risperidone was found to be effective and well tolerated.

Acute Disease↗