Attitudes toward Different Formulations of Psychotropic Drugs

Attitudes toward psychotropic drug treatment are likely to be a factor in medication adherence and outcome, but preferences regarding different drug formulations have been rarely assessed. To explore attitudes toward different drug formulations in a cross-sectional study in psychiatric patients and a comparison group of healthcare professionals. Inpatients (n = 59, age 46 ± 14 years, 63% female) and staff members (n = 96, age 40 ± 10 years, 65% female) of a psychiatric department were surveyed using a questionnaire on attitudes toward 18 possible application forms of psychotropic drugs including newer formulations such as fast-dissolving tablets. The questionnaire asked respondents to rate …

Patients' satisfaction with medication during psychiatric inpatient treatment

Carbohydrate-deficient transferrin (CDT) and HDL cholesterol (HDL) are highly correlated in male alcohol dependent patients.

Background: Serum levels of total HDL cholesterol (HDL) are reportedly influenced by recent alcohol intake. We examined the correlation between HDL cholesterol and widely used markers of excessive alcohol intake, such as carbohydrate-deficient transferrin (CDT), γ-glutamyl-transferase (GGT), or mean corpuscular volume of erythrocytes (MCV), of which CDT is thought to be the most specific. Methods: Several serological markers [i.e., CDT, GGT, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), MCV, and HDL] were determined in 100 actively drinking male patients with alcohol dependence (DSM-IV) and in 27 non-alcohol-dependent controls, according to routine procedures. Spearman…

P-515 - CGI Rating to predict antidepressant treatment under naturalistic conditions

Introduction Recent studies have shown that psychopathological rating by the Hamilton Depression Rating scale (HAMD) is well established and highly predictive for later response. In this study we aimed to find out if Clinical Global Impression (CGI) scale is suitable to guide antidepressive treatment under naturalistic conditions. Methods Inpatients with a major depressive disorder and treatment with citalopram were included and rated using in parallel the HAMD scale and the CGI scale weekly at baseline to day 35. According to CGI the sample has been divided in “CGI improver” (CGI = 2–4) and “CGI non-improver” (CGI = 5–6). Response was defined as HAMD sum score reduction by at least 50%. Re…

CNS manifestations of Fabry's disease

Summary Background Fabry's disease is a rare hereditary lysosomal storage disease with multiorgan involvement. Deficiency of α-galactosidase A activity leads to accumulation of neutral glycosphingolipids, especially in vascular endothelial and smooth-muscle cells. Along with progressive renal and cardiac dysfunction, stroke is a major and often life-threatening burden of the disease. Cerebral vasculopathy, confirmed by neuropathological, neuroradiological, and functional studies, occurs commonly and leads to ischaemic cerebrovascular events at an early age. Recent developments Fabry's disease is an X-linked disease and women have been regarded as only mildly affected carriers. However, rese…

Therapy of erectile dysfunction (ED) with sildenafil improves quality of life (QoL) and partnership (QoP)

According to Maslow [1] and others, higher levels of individual and social functioning can only be achieved and maintained, when more basic and particularly physiological levels of functioning are satisfactory and healthy (Fig. 1). Satisfactory partnership and sexuality are core aspects of human wellbeing through the complete course of adulthood. Sexual activity is a major determinant of sexual satisfaction [2]. In men and women, sexual dysfunction as a disorder of sexual desire, arousal, or orgasm, and/or sexual pain results in personal distress and reduced quality of life and interpersonal relationships [3, 4, 5, 6]. Erectile dysfunction (ED) as the inability to attain or maintain penile …

Melperone is an Inhibitor of the CYP2D6 Catalyzed O-demethylation of Venlafaxine

INTRODUCTION Melperone, a butyrophenone neuroleptic, is frequently used for its sleep-inducing properties. Despite its common use for more than 30 years, it is not yet characterized regarding its effects on cytochrome P450 s (CYPs). In an open pilot study, effects of melperone on the steady-state blood levels of venlafaxine, a recently introduced serotonin- and noradrenaline reuptake inhibiting antidepressant, were assessed. METHODS The dose-corrected serum concentrations of venlafaxine and O-desmethylvenlafaxine were analyzed retrospectively in a therapeutic drug-monitoring (TDM) database comprising 94 patients. In addition, three patients received venlafaxine and melperone concomitantly a…

Dimensionality of depression in acute schizophrenia: a methodological study using the Bech-Rafaelsen Melancholia Scale (BRMES).

Abstract Despite the great clinical importance of depressive symptoms in schizophrenia there is a lack of studies on the assessment and evaluation of depression in acutely psychotic patients. For the Bech-Rafaelsen Melancholia Scale (BRMES), among other advantages, the concept of unidimensionality was confirmed in patients with major depression by different methodological approaches including Rasch analysis. The present evaluation was designed to investigate the scale properties of the BRMES in acutely schizophrenic patients with particular emphasis on the dimensionality of the scale. Three different statistical approaches were used: principal component analysis in combination with computer…

Catecholamine Response Curves of Male Hypertensives Identified by Lehmacher's Two Sample Configural Frequency Analysis

A new application of LEHMACHER'S (1980) marginal homogeneity sign tests is given by analysis of bivariate response curves (or response surfaces) in two unpaired samples of hypertensive versus normotensive patients. Rationale and computations are illustrated by empirical data from sympathomedullary stress research.

A monoamine oxidase B gene variant and short-term antidepressant treatment response.

Genetic differences among patients suffering from Major Depression are likely to contribute to interindividual differences in medication treatment response. Thus, the identification of gene variants affecting drug response is needed in order to be able to predict response to psychopharmacological drugs. This study analyzed a possible association of the common A644G single nucleotide polymorphism (SNP) within intron 13 of the monoamine oxidase B (MAOB) gene with antidepressant treatment response. The study population consisted of n = 102 patients with major depression (criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; DSM-IV) participating in a randomized do…

Association analysis between variants of the interleukin-1beta and the interleukin-1 receptor antagonist gene and antidepressant treatment response in major depression

André Tadic1, Dan Rujescu2, Matthias J Müller3, Ralf Kohnen4, Hans H. Stassen5, Armin Szegedi6, Norbert Dahmen11Department of Psychiatry, University of Mainz, Germany; 2Department of Psychiatry, University of Munich, Germany; 3Clinic for Psychiatry and Psychotherapy, Marburg-Sued, Germany, and Clinic for Psychiatry and Psychotherapy, Giessen, Germany; 4IMEREM, Nuernberg, Germany; 5Department of Psychiatry, University of Zurich, Switzerland; 6Organon, Roseland, NJ, USAAbstract: This study investigated the possible association of the interleukin-1 beta (IL-1β) C-511T promoter polymorphism and the interleukin-1 receptor antagonist (IL-1Ra) (86bp)n variable number o…

Genetic polymorphisms of the dopamine D2 and D3 receptor and neuroleptic drug effects in schizophrenic patients

SEQUENTIALLY ADJUSTED RANDOMIZATION TO FORCE BALANCE IN CONTROLLED TRIALS WITH UNKNOWN PREVALENCE OF COVARIATES: APPLICATION TO ALCOHOLISM RESEARCH

In treatment outcome studies with small to medium sample sizes (n200), the balance of groups with regard to important factors, which sometimes occur at low prevalence, is indispensable for adequate interpretation. This study tested a method for use in clinical alcoholism research, an uncomplicated procedure for satisfactory randomization of patients to different treatments, taking into account relevant background variables.An easily applicable modification of Efron's biased coin method for the randomization of treatments within strata of unknown but low prevalence was compared with the original approach and alternative methods by computer simulation (10,000 runs). An application example for…

Distigmine bromide induced acute psychotic disorder in a patient with multiple sclerosis.

AbstractA female patient with multiple sclerosis (MS) suffered from an acute psychotic disorder after taking distigmine bromide for detrusor dysfunction. She showed a dramatic relief of her symptoms after the medication, distigmine bromide, was stopped. Distigmine is not supposed to penetrate the blood-brain barrier (BBB). However, in MS patients a leakage of the BBB could be hypothesized.

Dose-Related Effects of Amisulpride on Five Dimensions of Psychopathology in Patients With Acute Exacerbation of Schizophrenia

The present analysis investigated symptom-specific dose-response relationships of the atypical antipsychotic amisulpride (AMI) in schizophrenic patients. The effects of different AMI doses on five different symptom dimensions of the Brief Psychiatric Rating Scale (BPRS) were analyzed. Results on global efficacy and safety parameters have been previously published. Four AMI doses (100 mg/day [AMI100], 400 mg/day [AMI400], 800 mg/day [AMI800], 1200 mg/day) were compared with 16 mg haloperidol (HAL16) in a multicenter, double-blind, randomized, parallel-group, 4-week trial. A total of 319 patients with acute exacerbation of schizophrenia (DSM-III-R) were included. AMI100 was compared with the …

An overview of the clinical efficacy of mirtazapine

Mirtazapine is at least as effective as the tricyclic antidepressants and trazodone in a wide range of patient subgroups including in- and out-patients with moderate to severe depression. It also appears to be at least as effective as the serotonin and noradrenaline reuptake inhibitor venlafaxine in the treatment of severely depressed melancholic patients. When compared with the selective serotonin reuptake inhibitors (SSRIs), mirtazapine shows a significantly earlier onset of action. Further analysis of a study comparing mirtazapine with the SSRI paroxetine indicated that early improvement was a highly sensitive predictor of later stable response for both drugs. The positive predictive val…

Gruppentherapeutische Frühintervention für Patienten im Frühstadium der Alzheimererkrankung und deren Angehörige - Eine Pilotstudie

Subject Pilot study on an early-interventional group therapy for patients with incipient Alzheimer disease and their relatives. The present study investigates whether scientific progress in terms of earlier time of diagnostic certainty can be used for psychoeducation, maintenance of positive activities and prevention of comorbid depressive episodes. Methods 12 patients (66.8 +/- 5.8 years, MMSE 24.0 +/- 4.0) together with 12 relatives have been treated with a bi-weekly group therapy program. Results For the patients treatment resulted in reduced anxiety, anergia and withdrawal, for their relatives reduced sleep disturbances, irascibility, and aggressiveness have been found. Only one of the …

Functional relevance and diagnostic utility of ROI-based and voxel-based diffusion-tensor imaging analyses in mild cognitive impairment

TheMAOA T941G polymorphism and short-term treatment response to mirtazapine and paroxetine in major depression

This study investigated the possible association of the MAOA T941G gene variant with differential antidepressant response to mirtazapine and/or paroxetine in 102 patients with major depression (DSM-IV criteria) participating in a randomized double-blind controlled clinical trial. Female mirtazapine-treated patients homozygous for the T-allele had a significantly faster and better treatment response than TG/GG-patients. In males, we failed to show an association between MAOA T941G gene variant and mirtazapine response. In the paroxetine-treated group, there were no significant differences in treatment response between MAOA T941G genotype groups. Time course of response and antidepressant eff…

Serum levels of aripiprazole and dehydroaripiprazole, clinical response and side effects

Aripiprazole, a novel antipsychotic drug, is metabolized by CYP3A4 and CYP2D6 forming mainly its active metabolite dehydroaripiprazole. In this study, aripiprazole and dehydroaripiprazole serum levels of psychiatric patients were measured and related to dose, comedication, and clinical effects including therapeutic and side effects. Patients were treated with mean doses of 20 +/- 8 mg/day of aripiprazole (median 15 mg, range 7.5-60 mg). Serum levels correlated significantly with the dose (r = 0.419; P0.01), with a mean value of aripiprazole of 214 +/- 140 ng/ml. Mean concentrations of the active metabolite dehydroaripiprazole amounted to 40% of the parent compound. Comedication with CYP3A4 …

Functional implications of hippocampal volume and diffusivity in mild cognitive impairment.

Abstract Hippocampal atrophy has been related to mild cognitive impairment (MCI) and early Alzheimer disease (AD), but the diagnostic significance of cross-sectionally determined hippocampal volumes is still ambiguous. Diffusion-Tensor-Imaging (DTI) in MCI patients revealed an association of microstructural changes in hippocampal areas with verbal memory decline. MRI volumetry and DTI were combined to investigate 18 MCI patients attending a memory clinic, and 18 carefully age- and gender-matched healthy controls. Neuropsychological testing, high resolution T1-weighted volume MRI scans, and DTI scans with regions-of-interest in hippocampal areas were applied. Left hippocampal volume was sign…

Validating the DemTect with 18-Fluoro-2-Deoxy-Glucose Positron Emission Tomography as a Sensitive Neuropsychological Screening Test for Early Alzheimer Disease in Patients of a Memory Clinic

<i>Objectives:</i> The first study to validate the diagnostic value of the DemTect, a short neuropsychological screening test for dementia (8–10 min), using 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) in patients of a memory clinic. <i>Methods:</i> DemTect results were compared to the clinical diagnosis and to FDG-PET as a reference method for the early in vivo detection of Alzheimer’s disease (AD). <i>Results:</i> 38 patients (age 65.2 ± 9.8 years, 16 men, 22 women) were investigated using clinical standard examination, FDG-PET, and cranial magnetic resonance imaging. According to NINCDS-ADRDA and Petersen’s criteria, 18 patients had…

Patterns of response to serotonergic antidepressants

Stage-dependent agreement between cerebrospinal fluid proteins and FDG-PET findings in Alzheimer's disease.

Cerebral hypometabolism and abnormal levels of amyloid beta (Aβ), total (t-tau) and phosphorylated tau (ptau) proteins in cerebrospinal fluid (CSF) are established biomarkers of Alzheimer's disease (AD). We examined the agreement between these biomarkers in a single center study of patients with AD of severity extending over a wide range. Forty seven patients (MMSE 21.4 ± 3.6, range 13-28 points) with incipient and probable AD underwent positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) and lumbar puncture for CSF assays of Aβ1-42, p-tau181, and t-tau. All findings were classified as either positive or negative for AD. Statistical analyses were performed for the whole samp…

Differential effects of high-dose amisulpride versus flupentixol on latent dimensions of depressive and negative symptomatology in acute schizophrenia: an evaluation using confirmatory factor analysis.

While many acutely ill schizophrenic patients suffer from depressive symptoms, most studies on the efficacy of antipsychotic drugs focus on positive and negative symptoms. Dimensional models of schizophrenic symptoms, based on confirmatory factor analysis (CFA) using structural equation modelling, offer a methodological alternative to compare antipsychotics on empirically justified latent factors. The present report is a refined analysis of a published double-blind study on the D 2 /D 3 -selective antagonist amisulpride (ASP) versus the mixed D 1-5 /5-HT 2 antagonist flupentixol (FPX). CFA was applied to Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Bech-Raf…

Evaluation eines standardisierten Trainings für die "Positive and Negative Syndrome Scale" (PANSS)

Die vorliegende Arbeit umfasst 3 Untersuchungen zur Interrater-Reliabilitat der deutschen Version der “Positive and Negative Syndrome Scale for Schizophrenia” (PANSS). Zur Interrater-Reliabilitat und Trainierbarkeit der PANSS liegen im deutschen Sprachraum trotz der weiten Verbreitung der Skala bisher keine empirischen Daten vor. Bei 3 Stichproben mit insgesamt 47 Teilnehmern unterschiedlicher klinischer Erfahrung wurde ein standardisiertes PANSS-Rater-Training durchgefuhrt und evaluiert. Als Qualitatsmase fur das Training wurden die Ubereinstimmung mit einem Expertenstandard (K) und gewichtete Kappa-Koeffizienten (κw) berechnet. Als ein Hauptergebnis lasst sich feststellen, dass zur Erreic…

Early improvement under mirtazapine and paroxetine predicts later stable response with high sensitivity in patients with major depression

Antipsychotic effects and tolerability of the sigma ligand EMD 57445 (panamesine) and its metabolites in acute schizophrenia: an open clinical trial.

Antipsychotic efficacy and side effects of the selective sigma ligand EMD 57445 (panamesine) were investigated in 12 patients (6 males, 6 females) who met DSM-III-R criteria for schizophrenia. A 4-week open clinical study revealed only modest effects of EMD 57445 and its metabolites on positive and negative symptoms of schizophrenia. Extrapyramidal and other side effects were moderate, although a significant increase in mild dyskinetic movements was found. Five patients, four of whom were females, completed the trial. Dropouts were mainly due to treatment failure. Antipsychotic effects were significantly greater in female than male patients.

Cognitive Behavioral Therapy Versus Sertraline in Patients With Depression and Poorly Controlled Diabetes: The Diabetes and Depression (DAD) Study

OBJECTIVE This study compared the long-term efficacy of a diabetes-specific cognitive behavioral group therapy (CBT) with sertraline in patients with diabetes and depression who initially responded to short-term depression treatment. RESEARCH DESIGN AND METHODS A randomized controlled single-blind trial was conducted in 70 secondary care centers across Germany comparing 12 weeks of CBT with sertraline in 251 patients with type 1 or 2 diabetes (mean HbA1c 9.3%, 78 mmol/mol) and major depression (Structured Clinical Interview for DSM-IV [SCID]). After 12 weeks, treatment responders (≥50% reduction Hamilton Depression Rating Scale [HAMD-17]) were included in the 1-year study phase where CBT p…

Evaluation of standardized rater training for the Positive and Negative Syndrome Scale (PANSS)

The Positive and Negative Syndrome Scale (PANSS) is employed increasingly for the evaluation of therapeutic outcome in studies on schizophrenia. Rater training is important to improve the concordance and accuracy of ratings; however, there are no established guidelines for carrying out such training. We conducted rater training, under clinical conditions, of psychiatrists and clinical psychologists who were rather unfamiliar with the PANSS. Based on videotapes of PANSS interviews, all participants were trained during five successive standardized weekly sessions. The results were analyzed with respect to conventional criteria of concordance with standard expert ratings and interrater reliabi…

Reliability and validity of the German version of the European Addiction Severity Index (EuropASI).

This study provides data on the psychometric characteristics of the German version of the European Addiction Severity Index (EuropASI). The ASI is a frequently used clinical and research instrument that measures problem severity among people with substance dependence.The German ASI was used in a sample of 112 consecutively admitted male psychiatric inpatients seeking treatment for severe alcohol problems. The conceptual structure of the German ASI subscales was investigated by analyzing the intercorrelations of the severity ratings and composite scores. Internal consistency, interrater reliability and concurrent validity in terms of correlations with other assessment instruments were evalua…

Ultrastructural Hippocampal and White Matter Alterations in Mild Cognitive Impairment: A Diffusion Tensor Imaging Study

Mild cognitive impairment (MCI) is considered to be a transitional stage between normal aging and dementia. In Alzheimer’s disease (AD), white matter structural pathology is due to Wallerian degeneration and central angiopathy. However, in MCI patients, the presence and extent of white matter alterations as a possible correlate of impaired memory function and as predictor of subsequent progression to AD is not clarified yet. Diffusion tensor imaging (DTI) reveals the ultrastructural integrity of cerebral white matter tracts. Therefore, it could detect pathological processes that modify tissue integrity in patients with MCI. In our prospective study, conventional and diffusion tensor MR scan…

Quality of partnership in patients with erectile dysfunction after sildenafil treatment.

OBJECTIVE A comprehensive investigation on the quality of partnership of male patients with erectile dysfunction (ED) after treatment with sildenafil vs. untreated patients, as perceived by both the patients and their female partners. METHODS This report describes an observational, cross-sectional exploratory study comparing ED patients responsive to sildenafil with ED patients prior to therapy. Assessments included the 'International Index of Erectile Function' (IIEF) and the 'Partnerschaftsfragebogen' (PFB), a partnership questionnaire used in German-speaking countries. The comparability of the two study groups was examined using a stepwise logit model. Significant intergroup differences …

Predicting conversion to dementia in mild cognitive impairment by volumetric and diffusivity measurements of the hippocampus.

In our prospective study of diffusion tensor imaging (DTI), we measured hippocampal mean diffusivity (MD) and volumes in amnestic mild cognitive impairment (MCI). Thirteen MCI patients were followed-up by clinical assessment over a mean 112-year period. MCI patients who converted to dementia (6 of 13) during the observation period had slightly elevated left hippocampal mean diffusivity at baseline compared with MCI patients who remained clinically stable. Hippocampal volumes as well as baseline verbal memory and MMSE did not differ significantly between stable MCI patients and converters. Hippocampal diffusivity was superior to hippocampal volumes for prediction of conversion to dementia in…

The Calgary Depression Rating Scale for schizophrenia in a healthy control group: Psychometric properties and reference values

Abstract Background Assessment of depression in schizophrenia is of great importance as depressive signs and symptoms and suicidality are highly prevalent in patients with schizophrenic disorders. The Calgary Depression Rating Scale (CDSS) is the standard assessment instrument for that purpose due to its proven reliability and validity. However, so far no reference values derived from an adequate healthy sample have been published. Methods The present study analyzed CDSS item scores and summary scores in 154 healthy subjects (49% female, mean age 32.8 ± 11.7 years) selected from studies as controls for schizophrenic patients. Results The total CDSS score was 2.6 ± 2.7 (range 0–12), about 1/…

Color-coded diffusion-tensor-imaging of posterior cingulate fiber tracts in mild cognitive impairment.

Abstract Different processes like microvascular dysfunction, free radical toxicity, β-amyloid deposits, and Wallerian degeneration can cause functionally relevant disturbances of cerebral neuronal networks by myelin degeneration. Color-coded diffusion-tensor-imaging (ccDTI) allows the structural identification and quantification of myelinated fiber tracts. Particularly, posterior cingulate fiber tracts, which are regarded as important neuronal substrates of the network representing memory processing can be localized only imprecisely by conventional magnetic resonance imaging techniques. The posterior cingulate bundles were assessed by ccDTI in 17 patients with amnestic mild cognitive impair…

Experimental evidence for a motivational origin of cognitive impairment in major depression.

BackgroundDiagnostic criteria and empirical evidence support the existence of cognitive deficits in depression. However, depressed mood, loss of interest and low self-efficacy might influence cognitive performance.MethodGoal-setting instructions were used to promote motivation in depressed patients and control subjects during neuropsychological assessment. The resulting performance was compared with performance using standard instructions. Sixty in-patients with non-psychotic unipolar depression and 60 age- and education-matched healthy control subjects were assessed with standard neuropsychological tests [the Auditory Verbal Learning Test (AVLT), the Digit Symbol Test (DST), the Regensburg…

Nocturnal hormone profiles in patients with schizophrenia treated with olanzapine.

Summary Nocturnal hormone profiles were measured in patients with schizophrenia with predominantly negative symptoms both under drug-free baseline conditions and after subchronic administration of the atypical antipsychotic olanzapine, with the aim of characterizing its pharmacological properties on the neuroendocrine level. The following hormones were studied in the sleep laboratory under polysomnographic control: adrenocorticotrophic hormone, cortisol, growth hormone (GH), prolactin, testosterone, and melatonin. Blood samples were taken at regular time intervals over the night, and serum concentrations of the hormones were determined. Ten patients completed the study, two of them were exc…

Three dimensions of depression in patients with acute psychotic disorders: A replication study

Depressive symptoms in psychotic disorders are of high relevance but seem to be heterogeneous when assessed with a standard rating scale. The present analysis is a replication study on the dimensionality of the Bech-Rafaelsen Melancholia Scale (BRMES) in acutely psychotic patients with substantial depression defined according to a functional approach across the nosological borders of schizophrenia with major affective symptoms, schizoaffective disorder, depressed subtype, and major depression with psychotic features. The baseline data of 123 patients participating in a multicenter pharmacological trial were evaluated with structural equation models. A previously reported three-dimensional m…

The benefit from whole body acupuncture in major depression.

Background: In a single-blind placebo-controlled study design we investigated the efficacy of acupuncture additionally applied to drug treatment in major depression. Methods: We randomly included 70 inpatients with a major depressive episode in three different treatment groups: verum acupuncture, placebo acupuncture and a control group. All three groups were pharmacologically treated with the antidepressant mianserin. The verum group received acupuncture at specific points considered effective in the treatment of depression. The placebo group was treated with acupuncture at non-specific locations and the control group received pharmacological treatment plus clinical management. Acupuncture …

Therapeutic drug monitoring of tricyclic antidepressants: how does it work under clinical conditions?

Therapeutic drug monitoring (TDM) of tricyclic antidepressants (TCA) is established in the treatment of depression to optimize outcome and safety. However, there are few reports on TDM under naturalistic clinical conditions. In the present study, we investigated a TDM group (TDM) and a randomly assigned parallel group without TDM (no-TDM) while on TCA treatment. Serum levels were analyzed in both cohorts, but feedback and dose recommendation were only provided for the TDM group. Serum levels of TCA were assessed by high-performance liquid chromatography (HPLC). The outcome was measured weekly using the Hamilton Depression Rating Scale (HAMD), the Clinical Global Impressions Scale (CGI), and…

Narcoleptic and schizophrenic hallucinations

The differential diagnosis of narcolepsy versus schizophrenia is sometimes complicated by similar phenomenology, particularly when hallucinations predominate. REM sleep disturbances seem fundamental in the pathophysiology of narcolepsy, and REM sleep intrusions during periods of wakefulness are often associated with hallucinations also in healthy controls and in patients with other brain disorders including schizophrenia. This study used a semistructured interview to investigate different aspects of hallucinations (frequency, modality, content, and dependence on body posture) in 148 patients with narcolepsy, 21 patients with acute exacerbation of a schizophrenic disorder, and 128 healthy su…

Syndrome profiles in alcoholism and panic disorder with or without agoraphobia

It is proposed that alcoholism and panic disorder/agoraphobia demonstrate in part common genetic and environmental origins. Shared subthreshold symptom patterns in the parents' generation could confirm the proposed genetic role in alcoholism and panic disorder/agoraphobia, even if the parents do not fulfil the diagnostic criteria for a primary psychiatric diagnosis. This is the first family study of exploratively analyzing subthreshold symptoms in both disorders. The authors investigated families with panic disorder/agoraphobia and/or alcoholism with the Munich-Composite International Diagnostic Interview (M-CIDI). We documented the diagnoses according to Diagnostic and Statistical Manual o…

Gender aspects in the clinical treatment of schizophrenic inpatients with amisulpride: a therapeutic drug monitoring study.

INTRODUCTION: It is assumed that female and male schizophrenic patients respond differentially to acute and chronic treatment with antipsychotics because of pharmacokinetic and pharmacodynamic factors linked to hormonal and constitutional gender differences. However, to date no empirical evidence exists in support of this notion. METHODS: In a naturalistic clinical study, we investigated gender differences in a sample of schizophrenic inpatients with acute exacerbation treated with the atypical antipsychotic amisulpride, a selective dopamine D2/D3 receptor antagonist with proven antipsychotic efficacy. Prescribed amisulpride dose, plasma level, clinical response (CGI), and side effects (UKU…

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

AbstractTherapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug…

Drug combination treatment in acute and subacute states of schizophrenia and schizoaffective disorder

Study protocol of the Diabetes and Depression Study (DAD): a multi-center randomized controlled trial to compare the efficacy of a diabetes-specific cognitive behavioral group therapy versus sertraline in patients with major depression and poorly controlled diabetes mellitus

Background Depression is common in diabetes and associated with hyperglycemia, diabetes related complications and mortality. No single intervention has been identified that consistently leads to simultaneous improvement of depression and glycemic control. Our aim is to analyze the efficacy of a diabetes-specific cognitive behavioral group therapy (CBT) compared to sertraline (SER) in adults with depression and poorly controlled diabetes. Methods/Design This study is a multi-center parallel arm randomized controlled trial currently in its data analysis phase. We included 251 patients in 70 secondary care centers across Germany. Key inclusion criteria were: type 1 or 2 diabetes, major depress…

Subchronic Effects of Olanzapine on Sleep EEG in Schizophrenic Patients with Predominantly Negative Symptoms

Background It is well known that sleep disturbance is an integral symptom of schizophrenia. In recent studies, a deficit of delta sleep has been observed in schizophrenic patients. Antipsychotic drugs with serotonin (5-HT2) receptor-antagonistic properties are considered to have delta sleep promoting effects. We have investigated the effects of subchronic olanzapine treatment on sleep EEG in schizophrenic patients. Methods The effects of administration of olanzapine (15 to 20 mg) on sleep were studied for four weeks in 10 male, drug-free patients suffering from schizophrenia with predominantly negative symptoms. Conventional sleep EEG parameters were investigated at baseline and after treat…

Association Between Citalopram Serum Levels and Clinical Improvement of Patients With Major Depression

Imaging studies have shown that serum concentrations of the selective serotonin reuptake inhibitor citalopram correlate with serotonin transporter (5-HTT) occupancy in vivo. In patients with major depressive disorders treated with citalopram, 80% 5-HTT occupancy was considered to be necessary for maximal therapeutic effects, which requires citalopram serum concentrations of at least 50 ng/mL. The aim of this study was to compare treatment outcome in patients with citalopram serum concentrations greater than and less than 50 ng/mL after 7 days of treatment. This study included inpatients with acute major depressive disorder according to International Classification of Disease, 10th Revision …

Association of elevated phospho-tau levels with alzheimer-typical 18F-Fluoro-2-Deoxy-D-Glucose positron emission tomography findings in patients with mild cognitive impairment

Abstract Background Mild cognitive impairment is considered to be a transitional stage between normal aging and dementia. Phosphorylated tau protein in cerebrospinal fluid and even more decrements of cerebral glucose metabolism in parietal, temporal, or cingulate regions have shown favorable specificity for the diagnosis of Alzheimer dementia and could be useful supplementary tools to determine Alzheimer pathology in early stages. Methods We measured cerebrospinal fluid tau phosphorylated at threonine 181 protein, cerebrospinal fluid total tau, and cerebral glucose metabolism using 18F-fluoro-2-deoxy-D-glucose positron emission tomography in 16 patients with mild cognitive impairment and ag…

Cerebrospinal Fluid Tau Protein Levels and <sup>18</sup>F-Fluorodeoxyglucose Positron Emission Tomography in the Differential Diagnosis of Alzheimer’s Disease

<i>Aims:</i> In this study, we aimed to compare cerebrospinal fluid (CSF) levels of total tau (t-tau), phosphorylated tau (p-tau<sub>181</sub>) and positron emission tomography with <sup>18</sup>F-fluorodeoxyglucose (FDG-PET) in the differential diagnosis of Alzheimer’s disease (AD) under clinical conditions. <i>Method:</i> In a cross-sectional, blinded, single-center study, we examined a sample of 75 unselected memory clinic patients with clinical diagnoses of dementia of Alzheimer type (DAT; n = 24), amnestic mild cognitive impairment (MCI; n = 16), other dementias (n = 13) and nondemented controls (n = 22). Discriminative accuracy, sensitiv…

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 a…

Diagnostic utility of hippocampal size and mean diffusivity in amnestic MCI

Hippocampus atrophy is a frequent finding in mild cognitive impairment (MCI), whereas diffusion-tensor-imaging (DTI) has demonstrated its value to detect subtle brain tissue changes in several neuropsychiatric diseases including MCI. To compare the diagnostic accuracy of both methods, high resolution MRI scans for hippocampus volumetry, and co-registered DTI-scans for ROI-based mean diffusivity (MD) and fractional anisotropy (FA) were carried out in 18 patients with amnestic MCI (7 females, age 67.3+/-8.7 years, MMSE 25.2+/-2.2) and 18 controls (age 66.9+/-9.0 years, MMSE 28.7+/-1.0). Diagnostic properties of normalized hippocampus volume (HV) and DTI measures with regard to MCI status were…

CSF APPsα and Phosphorylated Tau Protein Levels in Mild Cognitive Impairment and Dementia of Alzheimer's Type

We exploratively measured APPs alpha, a secreted fragment of the non-amyloidogenic cleavage of amyloid precursor protein via a-secretase, and tau protein phosphorylated at threonine 181 (p tau) in the cerebrospinal fluid of 10 patients with mild cognitive impairment, 20 patients with dementia of Alzheimer's type, and 10 controls. Cerebrospinal fluid APPs alpha and p tau levels were correlated with cognitive performance. P tau levels were significantly elevated in mild cognitive impairment and in patients with dementia of Alzheimer's type, APPs alpha levels were significantly reduced in patients with dementia of Alzheimer's type compared to the controls. APPs alpha levels were associated wit…

Effects of Interrater Reliability of Psychopathologic Assessment on Power and Sample Size Calculations in Clinical Trials

Although rater training is increasingly used to improve the quality of the investigated outcome parameters, the reliability of assessments is not perfect. Thus, empirical reliability estimates should be used instead of theoretically assumed perfect reliability. Implications of the reliability of psychiatric assessments for sample size and power calculations in clinical trials are presented. The theoretical basis of sample size and power calculations using empirical reliability scores is delineated. Examples from contemporary research on schizophrenia and depression are used to illustrate several implications for study design and interpretation of results. The tremendous impact of the lack o…

Combination treatment with nefazodone and cognitive-behavioral therapy for relapse prevention in alcohol-dependent men: a randomized controlled study.

Background This study evaluated the serotonergic antidepressant nefazodone versus placebo and specific cognitive-behavioral therapy (CBT) versus nondirective group counseling (GC) for relapse prevention in alcohol dependence in a large prospective, randomized, and placebo-controlled double-blind study at 3 German university centers. Method 242 male patients fulfilling at least 5 criteria for alcohol dependence according to DSM-IV and ICD-10 were eligible, after detoxification, for one of the following treatment combinations: nefazodone + CBT, nefazodone + GC, placebo + CBT, and placebo + GC. Either nefazodone or placebo was administered throughout the evaluation period of 15 months. Either …

Increased hippocampal head diffusivity predicts impaired episodic memory performance in early Alzheimer's disease

Recent neuroanatomical and functional neuroimaging studies indicate that the anterior part of the hippocampus, rather than the whole structure, may be specifically involved in episodic memory. In the present work, we examined whether anterior structural measurements are superior to other regional or global measurements in mapping functionally relevant degenerative alterations of the hippocampus in Alzheimer's disease (AD). Twenty patients with early AD (MMSE 25.7+/-1.7) and 18 healthy controls were studied using magnetic resonance and diffusion-tensor imaging. Using a regions-of-interest analysis, we obtained volumetric and diffusivity measures of the hippocampal head and body-tail-section …

Detection of Depression in Acute Schizophrenia: Sensitivity and Specificity of 2 Standard Observer Rating Scales

Objective: To compare the psychometric properties of the Calgary Depression Rating Scale (CDRS) and the Hamilton Depression Rating Scale (HDRS) for severity assessment of depression in acute schizophrenia. Method: During clinical routine treatment, we investigated 119 inpatients with acute schizophrenia, using the CDRS, the HDRS, and a global 4-point Depression Severity Scale (DEP-SEV). We compared CDRS and HDRS sum scores regarding their diagnostic accuracy, with global severity of depression as the criterion. We estimated sensitivity and specificity on the basis of receiver operating characteristic curves. Results: According to global clinical ratings (DEP-SEV), 31% of patients had no dep…

Relationship of Psychiatric Experience and Interrater Reliability in Assessment of Negative Symptoms

Modulation of [18F]fluorodopa (FDOPA) kinetics in the brain of healthy volunteers after acute haloperidol challenge.

In animal studies, acute antipsychotic treatment was shown to enhance striatal DOPA-decarboxylase (DDC) activity. However, this phenomenon has not been demonstrated in humans by positron emission tomography (PET). Therefore, we investigated acute haloperidol effects on DDC activity in humans using [18F]fluorodopa (FDOPA) PET. Nine healthy volunteers were scanned with FDOPA in drug-free baseline conditions and after 3 days of haloperidol treatment (5 mg/day). A continuous performance test (CPT) was administered in both conditions. The net blood-brain clearance of FDOPA (K(in)app) in striatum, mesencephalon, and medial prefrontal cortex was calculated by volume-of-interest analysis. The macro…

Gender-specific associations of depression with positive and negative symptoms in acute schizophrenia

This clinical study analyzed gender-specific relationships of depression with other psychopathological and clinical variables in hospitalized patients with schizophrenia. During clinical routine treatment 119 inpatients with acute schizophrenia (DSM-IV) were investigated with the Calgary Depression Rating Scale for Schizophrenia (CDSS), the Clinical Global Impressions (CGI), and the Positive and Negative Syndrome Scale (PANSS). Depression scores of 77 male and 42 female patients (mean age 31.6+/-10.3 years) were related to background variables and to positive and negative symptom scores. Mean CDSS (5.8+/-5.6) and PANSS scores (total 76.9+/-22.1, positive symptoms 17.6+/-7.6, negative sympto…

Therapeutic monitoring of new antipsychotic drugs.

Typical antipsychotic drugs qualify for therapeutic drug monitoring (TDM) primarily for the following reasons: control of compliance and avoidance of extrapyramidal side effects by keeping chronic exposure to minimal effective blood levels. For the atypical antipsychotic clozapine, drug safety is another reason to use TDM. With regard to the new antipsychotics risperidone, olanzapine, quetiapine, amisulpride, ziprasidone, and aripiprazole, which have been introduced in the clinic during the last few years, the rationale to use TDM is a matter of debate. Positron emission tomography (PET), which enables measurement of the occupancy of dopamine D2 receptors, revealed that receptor occupancy c…

Mortality in affective disorders.

Abstract Background : To investigate the mortality rates in affective disorders due to unnatural and natural causes with respect to illness subtype and social–demographic features. Methods : Mortality data were determined from a prospective study of 354 outpatients with affective disorders during a follow-up period of 5 years. Death from natural and unnatural causes was compared to sex- and age-specific expectations in the general population. Standardized mortality rates (SMR) in diagnostic subgroups and the influence of social–demographic features were investigated. Results : The observed 30 deaths represented nearly three times (SMR, 2.9) the number expected on the basis of age- and sex-s…

Overlap between emotional blunting, depression, and extrapyramidal symptoms in schizophrenia

The Calgary Depression Rating Scale for Schizophrenia: development and interrater reliability of a German version (CDSS-G)

A German version of the Calgary Depression Rating Scale for Schizophrenia (CDSS-G) approved by the author of the original scale is presented comprising a semi-structured interview for 9 items to sensitively and specifically assess depression in schizophrenia and related disorders. The process of translation is outlined and the finally derived CDSS-G was investigated with respect to interrater reliability in three studies. To keep comparability with the CDSS source version a standard procedure was used. Two trained raters jointly assessed ten schizophrenic patients (study I). In a second study, videotapes with the CDSS-G were presented to clinically inexperienced raters (study II, N = 14/15)…

No Association Between the Dopamine D2 Receptor Taq I A1 Allele and Earlier Age of Onset of Alcohol Dependence According to Different Specified Criteria

BACKGROUND: The presence of the A1 allele of the dopamine D2 receptor TaqI restriction fragment length polymorphism has been reported to be associated with an earlier age of onset of alcohol dependence as a marker for severity. METHODS: We tested this hypothesis with special regard to the definition of the age of onset of alcoholism in 243 patients with alcohol dependence, according to DSM-IV criteria assessed by the standardized interview Munchner Composite International Diagnostic Interview (M-CIDI), consecutively admitted for detoxification. Additionally, the Addiction Severity Index (ASI) was performed. The TaqIA polymorphism was amplified by polymerase chain reaction (PCR), and the PCR…

Symptom-Triggered versus Standard Chlormethiazole Treatment of Inpatient Alcohol Withdrawal: Clinical Implications from a Chart Analysis

To evaluate clinical effectiveness and safety of 2 different detoxification treatment protocols, a chart analysis of hospital inpatients consecutively admitted for alcohol withdrawal during one year was undertaken. Records of 33 patients receiving symptom-triggered treatment (using a modified version of the revised Clinical Institute Withdrawal Assessment for Alcohol Scale) were compared with those of patients treated by applying a fixed-dose regimen (n = 32). Patients (45.3 ± 9.8 years, 21% female) of both groups were comparable regarding illness severity, epidemiologic parameters as well as complications during the observed treatment period. Under symptom-triggered therapy, chlormethiazol…

Functional relevant loss of long association fibre tracts integrity in early Alzheimer's disease.

Abstract The aim of our study was to quantify the structural integrity of the long association fibre tracts in early Alzheimer's disease (AD) and to correlate the findings with the cognitive performance of the patients. We conducted region-of-interest-based analyses of color-coded diffusion-tensor imaging in 12 patients with early AD (age 69.8 ± 8.0 years; MMSE 25.3 ± 1.8) and 16 age- and education-matched healthy controls. Early AD patients showed significantly decreased fractional anisotropy (FA) of the cingulate bundles and the inferior fronto-occipital fascicles bilaterally, whereas FA values of the superior longitudinal fascicles (second division) did not differ significantly between p…

Moderate and severe depression

Background: Despite its importance, no distinction between moderate and severe depression using the Montgomery–Asberg Depression Rating Scale (MADRS) based on a direct comparison with the Hamilton Depression Rating Scale (HAMD-17) is available. Methods: HAMD-17 and MADRS ratings from N=40 at least moderately depressed inpatients with major depression (DSM-III-R) were analyzed. Linear and non-parametric correlations were computed and a MADRS cut-off score for severe depression using an HAMD-17 score of at least 28 points as reference was estimated. Results: HAMD-17 and MADRS mean scores were 24.6±4.3 and 32.6±5.0 points, respectively. Linear correlation of both scores was r=0.70 (P<0.0005). …

Standardisierte Verlaufsdokumentation als Grundlage zur Verbesserung der Prozessqualit�t der station�ren psychiatrischen Behandlung

Es wird eine standardisierte Verlaufsdokumentation zur detaillierten Beschreibung und Analyse des Behandlungsprozesses fur stationare psychiatrische Patienten vorgestellt. Im Rahmen eines an der Psychiatrischen Klinik der Universitat Mainz durchgefuhrten Pilotprojekts, zunachst beschrankt auf Patienten mit einem depressiven Syndrom, wurde der mit Hilfe wochentlich durchgefuhrter psychopathologischer Ratings erfasste klinische Zustand zusammen mit den therapeutischen Masnahmen fur die einzelnen Patienten im Zeitverlauf abgebildet. Es hat sich gezeigt, dass die Visualisierung des Behandlungsprozesses die klinische Arbeit unterstutzen und die Anwendung von Therapiestandards bei klinischen Ents…

Relationship of subjective helplessness and pain perception after electric skin stimuli

Objective and subjective controllability of painful stimuli are important factors in pain perception. The present study investigated direct and indirect effects of uncontrollability on perceived pain intensity in humans. Forty-eight healthy male volunteers participated in a laboratory experiment using a reaction time paradigm to induce controllable or uncontrollable feedback conditions in two randomly selected groups. Under controllable conditions, unpleasant electric skin shocks were applied, only when the actual time exceeded an individual threshold; under uncontrollable conditions, skin shocks were applied randomly using a yoked control design. Subjective helplessness, perceived pain int…

FDG-PET and CSF phospho-tau for prediction of cognitive decline in mild cognitive impairment

Specific patterns of cortical glucose metabolism disturbances and increased CSF phospho-tau (p-tau(181)) concentrations could be demonstrated to predict cognitive decline and shift to dementia in amnestic mild cognitive impairment (MCI). But comparisons of both diagnostic tools have not been undertaken so far. The aim of the study was to compare (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) findings and CSF phospho-tau (p-tau(181)) measurements in the prediction of cognitive deterioration and conversion to dementia in MCI. During follow-up (mean 19 months) eight of 16 patients (50%) showed progressive cognitive decline, and four patients shifted to dementia. Patholog…

Depression, emotional blunting, and akinesia in schizophrenia

Depression, negative symptoms, and extrapyramidal signs (EPS) frequently occur together in schizophrenia. Their overlap is due partly to the lack of specificity of assessment instruments. However, to disentangle the three syndromes is clinically important as treatment of schizophrenia requires a differentiated approach. This study investigated the overlap between depression, emotional blunting as a core part of the negative syndrome, and akinesia as manifestation of EPS, using the Calgary Depression Rating Scale (CDSS), the Rating Scale for Emotional Blunting (SEB), and the akinesia score of the Simpson-Angus Scale (SAS) as the most specific assessment instruments presently available. We in…

Frequency and dependence on body posture of hallucinations and sleep paralysis in a community sample.

Amisulpride doses and plasma levels in different age groups of patients with schizophrenia or schizoaffective disorder.

Abstract Because of a unique pharmacodynamic profile, amisulpride seems appropriate for treatment of elderly patients with schizophrenia. In a large-scale naturalistic therapeutic drug monitoring study, daily amisulpride dose, trough and dose-corrected amisulpride plasma levels, co-medication, clinical effectiveness (CGI) and side effects (UKU) were compared between age groups in 395 patients with schizophrenia or schizoaffective disorder (46% women; mean age 39.1 ± 14.2 years, range 18–83 years) under amisulpride therapy. Mean amisulpride doses (574 ± 269 mg/day), plasma levels (304 ± 274 ng/mL), dose-corrected amisulpride plasma levels (C/D ratios, 0.52 ± 0.41 ng/mL:mg), clinical respons…

Differentiating moderate and severe depression using the Montgomery–Åsberg depression rating scale (MADRS)

MADRS cut-off scores for moderate and severe depression were estimated in relation to the Hamilton Depression Rating Scale (HAMD(17)) and the Clinical Global Impressions Scale (CGI).HAMD(17), MADRS, and CGI ratings from patients with major depression (DSM-IV) were analyzed (N=85). Receiver operating characteristics (ROC) curves were applied.Mean age was 51.4+/-14.5 years, 69% were female. Mean MADRS scores were 23.4+/-13.2, HAMD(17), MADRS, and CGI scores were highly correlated (r0.85; P0.0001). Best separation between moderate and severe depression according to CGI criteria was achieved with a MADRS score of 31 (sensitivity 93.5%, specificity 83.3%).Studies to validate severity gradations …

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 D2 and D3 dopamine (DA) receptors. Objectives: The aim of this study was to test, using single photon emission computed tomography (SPECT) and [123I]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 befo…

Fluvoxamine but not sertraline inhibits the metabolism of olanzapine: evidence from a therapeutic drug monitoring service.

Therapeutic drug monitoring data of the new atypical neuroleptic drug olanzapine were used to study interactions with the selective serotonin reuptake inhibitors fluvoxamine and sertraline. The distribution of the ratio of concentration/daily dose (C/D; ng/mL per mg/d) of olanzapine was compared in three groups: patients treated with olanzapine (n = 134), patients treated with olanzapine plus fluvoxamine (n = 10) concomitantly, and patients treated with olanzapine plus sertraline (n = 21) concomitantly. No significant difference was seen between the olanzapine and the olanzapine plus sertraline groups. Patients receiving fluvoxamine in addition to olanzapine had C/D ratios that were in the …

“Abnormal Response to Negative Feedback”

Zusammenfassung: Es wurden alkoholabhängige Patienten unter Stressbedingungen neuropsychologisch untersucht. Fragestellung: Zeigt sich wie bei depressiven Patienten eine abnorme Reaktion auf negative Rückmeldung oder gar eine generelle Stressanfälligkeit? Die alkoholabhängigen Patienten wurden in der Testbatterie zur Aufmerksamkeitsprüfung (TAP) nach negativer Rückmeldung tendenziell langsamer und die Kontrollpersonen tendenziell schneller. Insgesamt ergab sich ein signifikanter Unterschied in Visuellem Scanning und Reaktionswechsel. Damit ist die “abnormal response to negative feedback” nicht spezifisch für depressive Patienten. Unter 90 dBA Lärm als Stressor zeigten sich dagegen keine Ef…

Brain structural alterations in Fabry disease: ROI-based and voxel-based analyses of diffusion tensor imaging parameters

Early Improvement and Serum Concentrations of Citalopram to Predict Antidepressant Drug Response of Patients with Major Depression

Post hoc analyses of clinical trials have shown that early improvement around day 14 is highly predictive for later response. More- over, evidence has been given that suffi ciently high concentrations of antidepressant drugs in blood are required to attain response. In this study, we determined cut-off levels for citalo- pram serum concentrations and clinical improve- ment during the early phase of treatment to predict later response and the predictive power of these measures either alone or in combination. Methods: Inpatients with depressive disorder according to ICD-10 who received citalopram were included. Psychopathology was assessed by the 17-item Hamilton Depression (HAMD-17) rating s…

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 treatme…

Pathophysiologische Aspekte hirnstruktureller Veränderungen bei Morbus Fabry: Literaturübersicht

Fabry Disease (FD) is a rare X-linked lysosomal storage disorder caused by deficiency of alpha-galactosidase A (alpha-GAL) enzyme activity. Neutral glycosphingolipides (esp. Gb3) accumulate in lysosomes of several tissues, particularly in vascular endothelium and smooth muscle cells. Cerebral manifestations that might be mainly due to progressive cerebrovascular dysfunction, are one major and often life-threatening burden of the disease. We reviewed the present literature concerning brain structural alterations in FD and discuss the possibly relevant underlying pathophysiological aspects of these disturbances. Cerebrovascular events (TIA, stroke) occur in FD at a rather early age. In female…

Psychopathological predictors of suicide in patients with major depression during a 5-year follow-up.

SummaryObjective. It is widely known that the risk of suicide is higher in cases of major depressive disorders in comparison to the general population. The purpose of this study was to examine which psychopathologic symptoms during the index episode are predictors for an increased risk of suicide in the further course of major depression.Method. Mortality data were determined from a prospective study of 280 patients with major depression (DSM-III-R, single episode or recurrent) during a follow-up period of 5 years. The predictive power of different depressive symptoms including psychotic symptoms for suicide risk was investigated.Results.Patients who committed suicide(N = 16)during the foll…

Voxel based analyses of diffusion tensor imaging in Fabry disease

Background: Fabry disease (FD) is a lysosomal storage disorder that is associated with marked cerebrovascular disease. Conventional MRI shows an extensive load of white matter lesions (WMLs) already at an early stage in FD. Objective: Investigator independent and sensitive quantification of brain structural changes in clinically affected men and women with FD. Methods: The authors performed a voxel-based analysis of diffusion tensor images (DTI) in 25 FD patients and 20 age-matched normal controls. Results: DTI revealed significant increases of cerebral white matter diffusivity (MD) in FD patients that were pronounced in the periventricular white matter. Even the subgroup of patients withou…

Subchronic haloperidol downregulates dopamine synthesis capacity in the brain of schizophrenic patients in vivo

Udgivelsesdato: 2003-Apr The antipsychotic effect of neuroleptics cannot be attributed entirely to acute blockade of postsynaptic D(2)-like dopamine (DA) receptors, but may arise in conjunction with the delayed depolarization block of the presynaptic neurons and reduced DA synthesis capacity. Whereas the phenomenon of depolarization block is well established in animals, it is unknown if a similar phenomenon occurs in humans treated with neuroleptics. We hypothesized that haloperidol treatment should result in decreased DA synthesis capacity. We used 6-[(18)F]fluoro-L-dopa (FDOPA) and positron emission tomography (PET) in conjunction with compartmental modeling to measure the relative activi…

Therapeutic drug monitoring for optimizing amisulpride therapy in patients with schizophrenia.

Amisulpride is a clinically effective antipsychotic drug in a broad dose range with low propensity for extrapyramidal symptoms (EPS). Daily doses and plasma levels of amisulpride were analyzed within a large-scale therapeutic drug monitoring (TDM) survey to find plasma level ranges for optimized treatment under naturalistic conditions. Data of 378 schizophrenic patients treated with amisulpride (100-1550 mg) were included (40% female). Amisulpride plasma levels were analyzed at steady state; assessment comprised improvement (CGI-I) and side-effects, particularly EPS. For detection of cut-off values regarding non-response or EPS, receiver operating characteristics (ROC) curves were applied a…

Therapeutic Monitoring of Aripiprazole by HPLC with Column-Switching and Spectrophotometric Detection

Aripiprazole is a novel atypical antipsychotic drug for the treatment of schizophrenia and schizoaffective disorders (1)(2)(3). The drug is metabolized by the cytochrome P450 isoenzymes 3A4 and 2D6 (4). Because of high interindividual variability in the expression of these enzymes, the aripiprazole concentration varies among healthy individuals after administration of the drug (5). In patients, insufficient response or side effects, such as somnolence, akathisia, or nausea, may result from too low or too high drug concentrations. Therapeutic drug monitoring (TDM), which is established practice for many antipsychotic drugs (6)(7), may be helpful for patients treated with aripiprazole. We mea…

Spontaneous echo contrast caused by platelet and leukocyte aggregates?

Background and Purpose —Spontaneous echocardiographic contrast (SEC) is correlated to clinical thromboembolic events. We sought to determine the origin of SEC by utilizing direct analysis of left atrial blood. Methods —We examined the blood of 13 patients with and 19 without SEC. Blood samples were taken from the femoral vein and artery and from the right and left atria after transseptal puncture. Samples were incubated with fluorescence-labeled antibodies directed against the platelet (CD41a-PE, CD42b-PE, and CD62p-FITC) and leukocyte membrane epitopes (CD45-APC and CD14-FITC). The expressed epitopes were analyzed by dual laser flow cytometry immediately after blood withdrawal. Results —I…

CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine.

SUMMARY Background: Venlafaxine (V) is a mixed serotoninand noradrenaline reuptake inhibitor used as afirst-line treatment of depressive disorders. It ismetabolized primarily by the highly polymorphiccytochrome P450 (CYP) enzyme CYP2D6 to yielda pharmacologically active metabolite, O-des-methylvenlafaxine (ODV), and to a lesser extentby CYP3A4, to yield N-desmethylvenlafaxine(NDV).Objectives: The aim of this study was to assesswhether the O-demethylation phenotype of V hasan impact on the pharmacokinetics and clinicaloutcome.Method: In 100 patients treated with V, serumconcentrations of V, ODV and NDV and theratios of concentrations ODV/V as a measure ofO-demethylation were determined. Indiv…

Activity of the adenylyl cyclase in lymphocytes of male alcoholic patients is state dependent.

A decreased basal and/or stimulated activity of the G-protein/adenylyl cyclase (AC) system in peripheral blood cells has been proposed to represent a trait marker for alcoholism. However, AC activity may underlie state-dependent changes, which may impair a proper interpretation of AC activity measurements. Our study examined systematically the AC activity in peripheral lymphocytes of 73 male alcohol-dependent patients (according to DSM-IV criteria) at three different time points of measurement during the clinical course of detoxification (day 0 = at admission, while still ethanol-affected; day 2 = at the presumed peak of withdrawal symptoms; day E = after detoxification). Basal and stimulat…

Serum Levels of Sulpiride Enantiomers after Oral Treatment with Racemic Sulpiride in Psychiatric Patients: a Pilot Study1

Sulpiride (SULP), a substituted benzamide with high selectivity for D 2 -like dopamine receptors, has a chiral structure and is used in most countries as the racemate. In an open pilot study, we investigated 26 inpatients (13 female, 13 male) with schizophrenic or depressive disorder treated with SULP (mean daily dosage 64-1062 mg) administered orally, either as a monotherapy or as an add-on treatment to a stable and unchanged medication for 3-60 days. Serum levels of total SULP and of its enantiomers were measured by high-performance liquid chromatography (HPLC) procedures. Clinically relevant indicators of hepatic and renal function as well as retrospectively assessed clinical outcome par…

Reliability and validity of the form 90 interview.

&lt;i&gt;Objective:&lt;/i&gt; Alcohol consumption is a central variable in substance abuse research and treatment. The study reports the psychometric characteristics of the German version of the Form 90 interview for the assessment of recent alcohol consumption. &lt;i&gt;Method:&lt;/i&gt; Reliability was evaluated in a test-retest study (7 days) with 30 consecutively admitted psychiatric inpatients with alcohol dependence. Validity of Form 90 was assessed with a second sample of 60 alcohol-dependent inpatients. &lt;i&gt;Results:&lt;/i&gt; Form 90 demonstrated good to excellent retest reliability for the central variables of alcohol consumption. Retest reliability Pearson correlation coeffic…

The catechol-O-methyltransferase Val108/158Met polymorphism affects short-term treatment response to mirtazapine, but not to paroxetine in major depression.

The catechol-O-methyltransferase (COMT) is a major degrading enzyme in the metabolic pathways of catecholaminergic neurotransmitters such as dopamine and norepinephrine. This study investigated whether the functionally relevant Val(108/158)Met gene variant is associated with differential antidepressant response to mirtazapine and/or paroxetine in 102 patients with major depression (DSM-IV criteria) participating in a randomized clinical trial with both drugs. In patients treated with mirtazapine, but not paroxetine, allelic variations in the COMT gene were associated with differential response. COMT(VAL/VAL) and COMT(VAL/MET) genotype carriers showed a better response than COMT(MET/MET)-bea…

Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression

OBJECTIVE Current clinical knowledge holds that antidepressants have a delayed onset of efficacy. However, the delayed onset hypothesis has been questioned recently by survival analytical approaches. We aimed to test whether early improvement under antidepressant treatment is a clinically useful predictor of later stable response and remission. METHOD We analyzed data from a randomized double-blind controlled trial with mirtazapine and paroxetine in patients with major depression (DSM-IV). Improvement was defined as a 17-item Hamilton Rating Scale for Depression (HAM-D-17) score reduction of > or = 20%. Stable response was defined as > or = 50% HAM-D-17 score reduction at week 4 and week 6,…

Lower self-reported depression in patients with erectile dysfunction after treatment with sildenafil

Abstract Background: Depressive symptoms in men with erectile dysfunction (ED) may improve under successful ED treatment. Self-reported depressive symptoms were compared in men with ED after sildenafil treatment to a group of untreated patients. Methods: In an open study, self-reported depressive symptoms of 54 men after successful treatment with sildenafil (>4 weeks) and 51 men awaiting ED treatment were investigated with the Center of Epidemiologic Studies–Depression Scale (CES–D). CES–D items were subjected to an exploratory factor analysis and group differences in CES–D items and factors were analyzed. Results: Groups were comparable with respect to demographic characteristics and illne…

Neuropsychological status of alcohol-dependent patients: increased performance through goal-setting instructions.

Aims: The effects of goal-setting instructions on neuropsychological performance of alcohol-dependent patients and control subjects were assessed. Methods: 57 alcohol-dependent patients and 59 carefully age- and education-matched healthy control subjects underwent standard neuropsychological investigation. In addition, the goal-setting paradigm was used to systematically manipulate motivation. Participants were requested to calculate simple mathematical problems repeatedly within phases of a 2-min duration receiving normal or goal setting-instructions (to increase performance in the next phase by 20%). Results: The patients demonstrated deficits in standard neuropsychological tests. Patient…

hs-CRP Predicts Improvement in Depression in Patients With Type 1 Diabetes and Major Depression Undergoing Depression Treatment: Results From the Diabetes and Depression (DAD) Study

hs-CRP is elevated in depression (1), but evidence on decreases of hs-CRP during depression treatment or the role of hs-CRP in the prediction of response to depression treatment is still controversial (2,3). To date, no study has examined this association in patients with diabetes. As elevated hs-CRP increases the risk of diabetes complications in diabetes (4), we aimed to explore hs-CRP in patients with diabetes and major depression undergoing depression treatment based on the data of the Diabetes and Depression (DAD) study (5). Participants were randomized to 12 weeks (short-term phase) of diabetes-specific group cognitive behavioral therapy or sertraline treatment and followed up for 15 …

Standardized rater training for the Hamilton Depression Rating Scale (HAMD-17) in psychiatric novices.

Abstract Background: Despite the long and widespread use of the Hamilton Depression Rating Scale (HAMD), standardized reliability studies in inexperienced raters are not available. Methods: Rater training was carried using three videotaped interviews with depressed patients in 21 psychiatric novices who had negligible previous experience with the HAMD. Chance-corrected coefficients of rating agreement with expert standards (weighted κ , ICC) were computed for single items and the total score of the HAMD. Results: The results demonstrate sufficiently high interrater reliability ( κ >0.60) for most of the HAMD items and the total score (ICC=0.57–0.73). Three standardized HAMD training session…