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showing 10 items of 280 documents
Body mass index as a determinant of clozapine plasma concentrations: A pharmacokinetic-based hypothesis
2021
Background: Knowledge regarding the impact of body composition measures on pharmacokinetics of antipsychotics is limited. Aims: Our aim was to investigate the impact of body weight and body mass index on clozapine pharmacokinetics using a therapeutic drug monitoring database. Methods: A large therapeutic drug monitoring dataset of clozapine plasma concentrations considering three patient subgroups was analysed: a control group (CLZ0, 20–30 kg/m2, n=266), a group with high body mass index (CLZhigh, body mass index ⩾30 kg/m2, n=162) and with low body mass index values (CLZlow, body mass index <20 kg/m2, n=27). Comparisons of plasma and dose-adjusted plasma concentrations (C/D) of clozapine…
Serum levels of aripiprazole and dehydroaripiprazole, clinical response and side effects
2007
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 …
Dopamine D2/3 receptor occupancy by quetiapine in striatal and extrastriatal areas
2010
Quetiapine is next to clozapine an antipsychotic agent that exerts hardly any extrapyramidal side-effects at clinical efficacious doses. Some previous receptor occupancy studies reported preferential extrastriatal D2/3 receptor (D2/3R)-binding properties of second-generation antipsychotics and suggested this as possible reason for improved tolerability. This positron emission tomography (PET) investigation was designed to compare the occupancy of dopamine D2/3Rs by quetiapine in striatal and extrastriatal brain regions. Therefore, a cohort of 16 quetiapine-treated psychotic patients underwent an [18F]fallypride (FP) PET scan. Due to the high affinity of FP and its comparatively long half-li…
Efficacy and effectiveness of individual family intervention on social and clinical functioning and family burden in severe schizophrenia: a 2-year r…
2009
BackgroundEmpirical evidence of the efficacy and effectiveness of psychosocial family intervention and of the specificity of its effects on the course of schizophrenia is limited. The aim was to study the efficacy and effectiveness of psychosocial family intervention with regard to clinical and social functioning and family burden after controlling for compliance and several prognostic factors.MethodA 2-year randomized controlled trial with blind assessments. Fifty patients with DSM-IV schizophrenia and persistent positive symptoms and/or previous clinical relapse were allocated to psychosocial family intervention, individual counselling and standard treatment versus individual counselling …
Reduced oxytocin receptor gene expression and binding sites in different brain regions in schizophrenia: A post-mortem study
2016
Schizophrenia is a severe neuropsychiatric disorder with impairments in social cognition. Several brain regions have been implicated in social cognition, including the nucleus caudatus, prefrontal and temporal cortex, and cerebellum. Oxytocin is a critical modulator of social cognition and the formation and maintenance of social relationships and was shown to improve symptoms and social cognition in schizophrenia patients. However, it is unknown whether the oxytocin receptor is altered in the brain. Therefore, we used qRT-PCR and Ornithine Vasotocin Analog ([125I]OVTA)-based receptor autoradiography to investigate oxytocin receptor expression at both the mRNA and protein level in the left p…
Schizophrenic patients who smoke have a faster finger tapping rate than non-smokers
2002
The increased rate of smoking in schizophrenia patients remains unexplained and may reflect attempts at self-treatment. The effect sought from smoking may be related to nicotine's stimulating action. We tested this hypothesis by examining the relationship between smoking status and finger tapping rate, a measure of central processing, in schizophrenia patients treated with atypical antipsychotics. Smokers showed significantly faster finger tapping rates than non-smokers. This was not related to clinical state, illness chronicity, medication side-effects, antipsychotic dose or plasma concentrations. Nicotine can improve central processing in medicated schizophrenia patients and this may cons…
High striatal occupancy of D2-like dopamine receptors by amisulpride in the brain of patients with schizophrenia.
2003
The 'atypicality' of the antipsychotic drug, amisulpride, has been attributed to preferential extrastriatal binding. Previous investigations of striatal D2 receptor occupancy by amisulpride revealed conflicting results. The aim of this PET study was to measure the striatal occupancy by amisulpride and to correlate it with the corresponding drug plasma concentrations. Nine amisulpride-treated patients and 12 healthy volunteers serving as controls were studied with PET and [18F]desmethoxyfallypride. Occupancy values and plasma concentrations were nonlinearly fitted to an E max model. Results showed 43-85% (putamen) and 67-90% (caudate) D2-like receptor occupancy. Plasma amisulpride concentrat…
Subchronic Effects of Olanzapine on Sleep EEG in Schizophrenic Patients with Predominantly Negative Symptoms
2004
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…
Predictors of clinical remission following a first episode of non-affective psychosis: Sociodemographics, premorbid and clinical variables
2012
The aim of the study was to identify predictors associated with a lower likelihood of achieving a clinical remission 1 year after the first break of the illness. Participants were 174 consecutive subjects included in a first episode programme with no prior treatment with antipsychotic medication. Patients were assigned to haloperidol, olanzapine or risperidone in a randomized, open-label, prospective clinical trial. The main outcome variable was the remission criteria developed by the Remission in Schizophrenia Working Group. Clinical variables were included in a logistic regression analysis in order to predict the remission state at 1 year. At 1 year, 31% of patients met criteria for remis…
Dopamine D2 Receptor Occupancy Estimated From Plasma Concentrations of Four Different Antipsychotics and the Subjective Experience of Physical and Me…
2019
Background Impaired subjective well-being in schizophrenia patients treated with antipsychotics has often been linked inter alia to the antidopaminergic effects of medication. Thus, it is important to capture the association between striatal dopamine D2 receptor occupancy (D2-RO) and global subjective well-being. We examined this association using data from our multicenter, randomized, double-blind Neuroleptic Strategy Study (NeSSy). Methods An innovative double randomization process was used for allocation of patients to the specific treatment groups. Plasma drug concentrations were measured after 6 and 24 weeks of treatment to obtain the estimated D2-RO (eD2-RO) relative to literature val…