What are depressive symptoms in acutely ill patients with schizophrenia spectrum disorder?

BACKGROUND: Aim was to examine depressive symptoms in acutely ill schizophrenia patients on a single symptom basis and to evaluate their relationship with positive, negative and general psychopathological symptoms. METHODS: Two hundred and seventy-eight patients suffering from a schizophrenia spectrum disorder were analysed within a naturalistic study by the German Research Network on Schizophrenia. Using the Calgary Depression Scale for Schizophrenia (CDSS) depressive symptoms were examined and the Positive and Negative Syndrome Scale (PANSS) was applied to assess positive, negative and general symptoms. Correlation and factor analyses were calculated to detect the underlying structure and relationship of the patient's symptoms. RESULTS: The most prevalent depressive symptoms identified were depressed mood (80%), observed depression (62%) and hopelessness (54%). Thirty-nine percent of the patients suffered from depressive symptoms when applying the recommended cut-off of a CDSS total score of >6 points at admission. Negligible correlations were found between depressive and positive symptoms as well as most PANSS negative and global symptoms despite items on depression, guilt and social withdrawal. The factor analysis revealed that the factor loading with the PANSS negative items accounted for most of the data variance followed by a factor with positive symptoms and three depression-associated factors. LIMITATIONS: The naturalistic study design does not allow a sufficient control of study results for the effect of different pharmacological treatments possibly influencing the appearance of depressive symptoms. CONCLUSION: Results suggest that depressive symptoms measured with the CDSS are a discrete symptom domain with only partial overlap with positive or negative symptoms.

[Antipsychotics for treatment of neuropsychiatric disorders in dementia]. / Antipsychotika zur Behandlung neuropsychiatrischer Störungen bei Demenz.

Antipsychotics, when used to treat neuropsychological symptoms associated with dementia, are associated with low effectiveness but a high risk of side effects. Some of these unwanted effects are severe and include an increased rate of cerebrovascular events and increased mortality. Although neuropsychiatric symptoms are frequently associated with dementia, it appears that antipsychotics are often used without clear indications and for too long time periods. Antipsychotics should be used only when all non-pharmacological strategies have failed. A clear definition of the treatment target in advance and a continuous monitoring of the therapy are mandatory.

Insight in schizophrenia-course and predictors during the acute treatment phase of patients suffering from a schizophrenia spectrum disorder.

BACKGROUND: To analyse insight of illness during the course of inpatient treatment, and to identify influencing factors and predictors of insight. METHODS: Insight into illness was examined in 399 patients using the item G12 of the Positive and Negative Syndrome Scale ("lack of insight and judgement"). Ratings of the PANSS, HAMD, UKU, GAF, SOFAS, SWN-K and Kemp's compliance scale were performed and examined regarding their potential association with insight. The item G12 was kept as an ordinal variable to compare insight between subgroups of patients. RESULTS: Almost 70% of patients had deficits in their insight into illness at admission. A significant improvement of impairments of insight during the treatment (p<0.0001) was observed. At admission more severe positive and negative symptoms, worse functioning and worse adherence were significantly associated with poorer insight. Less depressive symptoms (p=0.0004), less suicidality (p=0.0218), suffering from multiple illness-episodes (p<0.0001) and worse adherence (p=0.0012) at admission were identified to be significant predictors of poor insight at discharge. CONCLUSION: The revealed predictors might function as treatment targets in order to improve insight and with it outcome of schizophrenia.

Response and remission of subjective well-being in patients suffering from schizophrenia spectrum disorders.

BACKGROUND: Purpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being. METHOD: The subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logistic regression and CART analyses were used to determine valid predictors of subjective well-being outcome. RESULTS: Twenty-nine percent of the patients were detected to be SWN-K early responders, 40% fulfilled criteria for response in subjective well-being and 66% fulfilled criteria for remission concerning subjective well-being. Among the investigated predictors, SWN-K early improvement and the educational status were significantly associated with SWN-K response. The SWN-K total score at baseline showed a significant negative predictive value for response. Baseline SWN-K total score, PANSS global subscore, and side effects as well as the educational status were found to be significantly predictive for remission. CONCLUSIONS: Depressive symptoms should be radically treated and side effects closely monitored to improve the patient's subjective well-being. The important influence of subjective well-being on overall treatment outcome could be underlined.

Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale.

OBJECTIVE: To examine depressive symptoms, their course during treatment, and influence on outcome. METHOD: Weekly Calgary Depression Scale for Schizophrenia ratings were performed in 249 inpatients with schizophrenia. Early response was defined as a 20% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia from admission to week 2, response as a 50% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) from admission to discharge and remission according to the consensus criteria. RESULTS: Thirty six per cent of the patients were depressed at admission, with 23% of them still being depressed at discharge. Depressed patients scored significantly higher on the PANSS negative and general psychopathology subscore, featured more impairments in subjective well-being (P < 0.0001) and functioning (P < 0.0001). They suffered from more suicidality (P = 0.0021), and had greater insight into their illness (P = 0.0105). No significant differences were found regarding early response, response, and remission. CONCLUSION: Patients with depressive symptoms should be monitored closely, given the burden of negative symptoms, their impairments in well-being and functioning and the threat of suicidality.

A critical analysis and discussion of the appropriateness of the schizophrenia consensus remission criteria in clinical pharmaceutical trials.

BACKGROUND: The aim of this paper is to apply the proposed consensus remission criteria to an acutely ill inpatient sample at admission and evaluate their adaptability in this patient population and pharmaceutical trials. METHODS: The Remission in Schizophrenia Working Group's consensus criteria were applied to 272 acutely ill schizophrenia patients. Patients were examined using the PANSS, HAMD, UKU and SWN-K total scales at admission as well as the GAF, SOFAS and the Strauss-Carpenter Prognostic Scale. Sociodemographic and clinical baseline variables were assessed using a standardized documentation system. RESULTS: 33 patients (12%) fulfilled the symptom severity component of the proposed remission criteria already at baseline. Almost no significant differences were found when comparing patients with achieved and failed symptom severity component that would explain the hospitalization of the patients with achieved criteria despite their apparently mild psychopathological symptoms. The only explainable difference was that patients with an achieved symptom severity component had received significantly more antipsychotics and had suffered from significantly more life events before admission. CONCLUSION: The present results raise the question whether the symptom severity threshold is adequate to identify patients in remission when applied in clinical trials.

Time course of antipsychotic treatment response in schizophrenia: results from a naturalistic study in 280 patients.

OBJECTIVE: To describe the course of positive and negative symptoms during inpatient treatment and examine remission and response rates under routine clinical care conditions. METHODS: Two hundred and eighty inpatients with schizophrenia (DSM-IV criteria) were assessed with the Positive and Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the symptom-severity component of the consensus criteria (Remission in Schizophrenia Working Group) as a rating of three or less in the relevant PANSS items at discharge, and response as a reduction of at least 20% in the PANSS total score from admission to discharge. RESULTS: The mean duration of inpatient treatment was 54.8 days. Of the total sample, 78.5% achieved the criteria for response and 44.6% those for remission. Mean PANSS total scores decreased from 72.4 at admission to 52.5 at discharge (p<0.001). A reduction in PANSS total scores was found from visit to visit, up to week 8. The most pronounced decline was observed within the first two weeks of treatment. CONCLUSION: Response rates were comparable to those found in efficacy studies, and remission rates were slightly higher. This may be explained by differences in the selection and the treatment of patients. Nevertheless, the findings might indicate that a complex naturalistic treatment approach is beneficial in terms of effectiveness.

Outcome of suicidal patients with schizophrenia: results from a naturalistic study.

OBJECTIVE: Purpose was to assess suicidality before and at the time of admission in patients with schizophrenia and compare outcome differences. METHOD: Biweekly PANSS (Positive and Negative Syndrome Scale), HAMD (Hamilton Depression Rating Scale) and UKU (Udvalg for Klinske Undersogelser Side Effect Rating Scale) ratings were evaluated in 339 in-patients with schizophrenic spectrum disorders. Response was defined as an initial 20% PANSS total score reduction at discharge, remission was defined according to the proposed consensus criteria by the Remission in Schizophrenia Working Group. RESULTS: Suicidal patients (22%) scored significantly higher on the PANSS negative subscore, PANSS insight item and HAMD total score at admission and at discharge. They developed significantly more side effects. No differences were found concerning response and remission between the two patient subgroups. CONCLUSION: Despite receiving significantly more antidepressants the suicidal patients suffered from significantly more depressive symptoms up to discharge, yet without differing regarding response and remission.

Early improvement as a predictor of remission and response in schizophrenia: Results from a naturalistic study.

OBJECTIVE: To examine the predictive validity of early improvement in a naturalistic sample of inpatients and to identify the criterion that best defines early improvement. METHODS: Two hundred and forty-seven inpatients who fulfilled ICD-10 criteria for schizophrenia were assessed with the Positive And Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the recently proposed consensus criteria, response as a reduction of at least 40% in the PANNS total score from admission to discharge. RESULTS: Receiver operating characteristic (ROC) analyses showed that early improvement (reduction of the PANSS total score within the first 2 weeks of treatment) predicts remission (AUC=0.659) and response (AUC=0.737) at discharge. A 20% reduction in the PANSS total score within the first 2 weeks was the most accurate cut-off for the prediction of remission (total accuracy: 65%; sensitivity: 53%; specificity: 76%), and a 30% reduction the most accurate cut-off for the prediction of response (total accuracy: 76%; sensitivity: 47%; specificity: 90%). CONCLUSION: The findings of clinical drug trials that early improvement is a predictor of subsequent treatment response were replicated in a naturalistic sample. Further studies should examine whether patients without early improvement benefit from an early change of antipsychotic medication.

Standardized remission criteria in schizophrenia: descriptive validity and comparability with previously used outcome measures.

INTRODUCTION: Standardized consensus criteria for remission in schizophrenia were recently proposed. As yet, the validity of these criteria and their comparability with previously used outcome measures are unclear. METHODS: The symptom-severity component of the proposed remission criteria was applied to 288 inpatients who fulfilled the ICD-10 criteria for schizophrenia. Global functioning and psychopathological symptoms were assessed using GAF, PANSS, SANS, HAM-D and CDSS. RESULTS: When patients with symptom remission at discharge from hospitalization (n=158, 54.9%) were compared to those without symptom remission, significant differences were found with respect to the global functioning (GAF) and all observed psychopathological symptom dimensions. The percentage agreement with previously used outcome measures ranged between 52.6 and 80.0%, the kappa values between 0.120 and 0.594. A moderate accordance (kappa value: 0.495) was found with a Clinical Global Impression (CGI) severity score of three or less. DISCUSSION: The results indicate a high descriptive validity of the symptom-severity component of the proposed remission definition. However, the new criteria differ partially from previously used outcome measures. This aspect should be considered in the interpretation of clinical trials.

[Substance-induced disorders: moving towards DSM-V and ICD-11]. / Substanz-bezogene Störungen: Auf dem Weg zu ICD-11 und DSM-V.

The development of substance abuse disorders (SUD) for DSM-V is put into perspective according to an expert meeting organized by APA and chaired by M.A. Schuckit and J.B. Saunders. Substantial compatibility with ICD-11 of WHO was expected to be achieved. A dependence syndrome, a non-dependence category as well as a subthreshold condition is supposed to be included in the SUD section in DSM-V. Categorical criteria will possibly be supplemented by dimensions conceptualized as quantitative formulations of criteria content. General and substance-specific criteria may be included for dependence. The comorbidity problem requires more research to separate substance-induced from substance-independent mental disorders in patients with SUDs. It was an open discussion, whether the aim to include biological criteria for better defining of SUDs will be achieved in DSM-V.

Galantamine: a cholinergic patch in the treatment of alcoholism: a randomized, placebo-controlled trial.

OBJECTIVES: The involvement of the central cholinergic system in alcohol abuse behavior is well known. It is possible that the reinforcing effects of ethanol are partially mediated by nicotinic receptors, which modulate neurotransmitter release. It was demonstrated that the application of a cholinesterase inhibitor reduces alcohol consumption in alcohol-preferring rats. This suggests that galantamine (GAL), a cholinesterase inhibitor, could be effective when seeking to prolong abstinence in recently detoxified alcoholics. This study represents the first reported clinical trial of a cholinergic drug in alcohol-relapse prevention. PATIENTS AND METHODS: We investigated the efficacy and safety of GAL by conducting a 24-week randomized, placebo-controlled, multicentric clinical trial on 149 recently detoxified alcoholics. Survival analyses (Kaplan-Meier) were performed to reveal evidence of prolonged abstinence periods in patients who received GAL. RESULTS: Our findings did not support our hypothesis. GAL did not extend the time to first severe relapse. However, additional post hoc analyses suggest that relapsed patients treated with GAL consume less ethanol per drinking day than patients treated with placebo. CONCLUSIONS: GAL seems to be ineffective when used in relapse prevention of detoxified alcoholics. It is possible that alcohol needs to be "on board" for GAL to be beneficial. This could explain why our post hoc analysis showed that GAL possibly reduces the alcohol consumption of relapsers. If confirmed, GAL could play a role in the reduction of harmful alcohol use and at-risk consumption.

[Psychiatric and neuropsychological signs and symptoms in patients with fabry disease: literature review]. / Psychiatrische und neuropsychologische Auffälligkeiten bei Patienten mit Morbus Fabry: Literaturübersicht.

Fabry Disease (FD) is an X-linked lysosomal storage disorder (prevalence about 1 : 100 000) caused by a genetic defect associated with a lack of alpha-galactosidase A (alpha-GAL) enzyme activity. As a consequence, neutral glycosphingolipides can not be cleaved and metabolized, and accumulate in lysosomes of several tissues, particularly in vascular endothelium and smooth muscle cells. The most prominent symptoms comprise pain attacks and acroparesthesia, angiokeratoma, corneal opacity, renal and cardiac dysfunction, hypo- and anhidrosis, gastrointestinal symptoms, and cerebrovascular dysfunction with vertigo, headache, and cerebral ischemia. Characteristic symptoms of FD can occur in male and female patients with the same prevalence, while females with FD seem to be less severely affected. The course of untreated illness is progressive with considerable interindividual variability. Since 2001 two enzyme replacement therapies are approved which can possibly stop the disease progress and alleviate symptoms. The very few reports and clinical observations have shown that a very high proportion of FD patients develop neuropsychiatric symptoms. However, accurate data are lacking. Although the pathophysiologic mechanisms are quite unknown, it is surmised that sphingolipid deposits in the endothelium of small cerebral vessels lead to regional cerebral ischemia accompanied by neuropsychiatric symptoms and deficits. Furthermore, patients with FD are chronically distressed by pain attacks and additional somatic and psychological impairment. Frequently, pain attacks are triggered by psychosocial stress. The high interindividual variability can, thus, also be interpreted on the basis of existing stress and coping models. The present paper will review the presently available psychiatric and neuropsychological findings in FD and will discuss difficulties associated with classification and differential diagnosis of psychiatric disorders occurring in patients with FD.

Prescribing practices in German and Swiss psychiatric university and in non-university hospitals: national differences.

OBJECTIVE: There are great variations between hospitals in the way drugs are prescribed, and these variations may be due to multiple factors such as local prescribing traditions, pharmacoeconomic considerations, drug availability, regional differences of population, disease prevalence etc. Available studies on prescribing habits, apart from studies performed in a unique center, have until now been mainly restricted to single countries or regions and the comparisons across countries or regions have often been limited by the use of diverse methodologies and definitions. The aim of the present study was to compare drug prescriptions between German and Swiss psychiatric services with regard to their preference of newer psychotropics. MATERIAL AND METHODS: Five psychiatric hospitals, associated to the AMSP project, were chosen to represent Swiss and German clinics, university and non-university settings. Data were available from one index day on 572 patients and 1,745 prescriptions. The comparisons were adjusted for age and gender. RESULTS: There was a significant difference (p < 0.001) with regard to the prescription of newer antidepressants (NAD), Swiss clinicians giving proportionally more (65.2%) than the German psychiatrists (48.3%). No significant difference was, on the other hand, found as to the proportion of atypical antipsychotics, the lack of difference being due to the higher proportion of clozapine among the atypical antipsychotics in Germany. CONCLUSION: There seems, therefore, to be a higher propensity for Swiss hospital psychiatrists to prescribe newer antidepressants. This seems to be due to national or regional prescribing traditions. Further studies are needed to investigate the economical influences on antidepressant prescribing in Swiss and German clinics.

[Helping smokers kick the habit]. / Die besten Argumente für den Ausstieg aus der Tabaksucht. Motivator Hausarzt.

The family doctor has an increasingly important role to play as a "gatekeeper", with many advantages for the initiation and implementation of a successful weaning program. Controlled studies have demonstrated the effectiveness of a short-term intervention based on motivational talks by the family doctor together with the application of such weaning drugs as nicotine substitutes and bupropion. The latter substance should be offered to adult smokers consuming in excess of ten cigarettes daily. The chances that a smoker can successfully stop smoking is doubled by the use of weaning medication. Ideally,the physician should, at the same time, draw the patient's attention to the significance of a healthy diet and physical exercise.

The AMUP study for drug surveillance in psychiatry - a summary of inpatient data.

From 1979 to 1989 the AMUP study (AMUP = Arzneimittelüberwachung in der Psychiatrie) was conducted in two psychiatric hospitals in Germany with the aim to provide a systematic and standardized assessment of all adverse reactions to psychotropic drugs under conditions of routine practice. A total of 60.7 % of patients experienced at least one adverse drug reaction (ADR) with probable or definite causality during their stay in the hospital; 37.1 % of patients exhibited ADRs that had some therapeutic impact on further treatment. ADRs that led to drug discontinuation were observed in 8.6 %. This rate ranged from 9.5 to 5.1 % for haloperidol and perazine, the most common neuroleptics at that time; sedating antidepressants (AD) rated lower than non-sedating (amitriptyline 5.1 %, clomipramine 10.4 %). Lithium salts, antiparkinson drugs, and benzodiazepines were associated with considerably lower rates of ADRs than neuroleptics or antidepressants. Severe ADRs occurred in 1.4 % of exposed patients (e. g., toxic delirium, grand mal seizures, malignant neuroleptic syndrome, or agranulocytosis). The AMUP data suggest that administration of psychotropic drugs in psychiatric hospitals at that time was a safe, but also inconvenient treatment for many patients due to a wide range of bothersome side effects that compromised patient compliance. The data can serve as a reference base for comparisons with newer compounds introduced to the market over the last decade such as serotonin reuptake inhibitors (SSRIs) and other new AD, atypical neuroleptics, or other new generation psychotropic drugs.

Severe adverse drug reactions of antidepressants: results of the German multicenter drug surveillance program AMSP.

The goal of the German drug safety program in psychiatry AMSP (Arzneimittelsicherheit in der Psychiatrie) is the assessment of severe or new adverse drug reactions (ADRs). Here we report on 53,042 of 122,562 patients treated with antidepressants who were monitored from 1993 to 2000 in 35 psychiatric hospitals in German-speaking countries. The overall incidence of severe ADRs of antidepressants was 1.4 % of exposed patients; when only ADRs rated as probable or definite were considered, a rate of 0.9 % in patients treated with antidepressants was observed. ADR rates were higher for TCAs (imputed in 1.0 % of patients overall, respectively in 0.6 % of patients when only ADs were imputed) and lower for MAO inhibitors and SSRIs (0.7 % for both, respectively 0.3 % and 0.4 %). Within the TCA group there was a difference among clomipramine (2.1 %, respectively 1.0 %), amitriptyline (1.0 %, respectively 0.6 %), and doxepin or trimipramine (both 0.6 %, respectively 0.3 %). With regard to single SSRI, similar rates were observed for paroxetine (0.8 %, respectively 0.5 %) and for citalopram (0.7 %, respectively 0.4 %). Of the new dual-acting antidepressants, venlafaxine ranged at 0.9 %, (respectively 0.5 %) and mirtazapine at 0.6 % (respectively 0.5 %). In particular, TCAs were associated with known risks, such as toxic delirium, grand mal seizures, and hepatic (i. e., increased liver enzymes), urologic (i. e., urinary retention), allergic (i. e., exanthema), or cardiovascular (i. e., mainly orthostatic collapse) reactions. In SSRI-treated patients (non-delirious) psychic and neurological ADRs were most prominent, followed by gastrointestinal, dermatologic, and endocrinological/electrolyte reactions, with agitation, hyponatremia (probably as part of the SIADH syndrome and associated with severe neurologic or psychiatric symptoms in 64 % of all cases), increased liver enzymes, nausea, and the serotonin syndrome as leading unwanted symptoms. Venlafaxine (in the immediate-release formulation) was associated with adverse CNS and somatic symptoms such as severe agitation, diarrhea, increased liver enzymes, hypertension, and hyponatremia. Mirtazapine was mostly connected with increased liver enzymes, cutaneous edema, and collapse, but with no case of significant hyponatremia. For drugs that potently inhibit serotonin uptake, serum sodium concentration should be controlled when applied in high-dose therapy or in vulnerable patients.

[Early diagnosis of alcohol abuse and alcohol dependence in general practice]. / Alkoholmissbrauch und Alkoholabhängigkeit. Geniesst lhr Patient noch oder ist er schon Alkoholiker?

The doctor's office offers the best chance of an early diagnosis of alcohol-related disorders. The physician can make the most of his opportunity by always taking this possibility into account in patients with unspecific symptoms. Since so-called low-risk alcohol consumption may develop into damaging drinking and finally addictive drinking leading to dependence, the physician must be familiar with the features of these different drinking patterns to be able to intervene prophylactically in the early forms, and therapeutically in later stages. Diagnostic talks with the patient should always contain elements of motivational interviewing so as to enable the physician to react appropriately to the degree of readiness of the patient to make necessary changes in his lifestyle.