Therapeutic Drug Monitoring (TDM) is a valid tool to optimise pharmacotherapy. It enables the clinician to adjust the dosage of drugs according to the characteristics of the individual patient. In ...psychiatry, TDM is an established procedure for lithium, some antidepressants and antipsychotics. In spite of its obvious advantages, however, the use of TDM in everyday clinical practice is far from optimal. The interdisciplinary TDM group of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has therefore worked out consensus guidelines to assist psychiatrists and laboratories involved in psychotropic drug analysis to optimise the use of TDM of psychotropic drugs. Five research-based levels of recommendation were defined with regard to routine monitoring of plasma concentrations for dose titration of 65 psychoactive drugs: (1) strongly recommended, (2) recommended, (3) useful, (4) probably useful and (5) not recommended. A second approach defined indications to use TDM, e. g. control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic particularity concerning the drug metabolism, children, adolescents and elderly patients. Indications for TDM are relevant for all drugs either with or without validated therapeutic ranges. When studies on therapeutic ranges are lacking, target ranges should be plasma concentrations that are normally observed at therapeutic doses of the drug. Therapeutic ranges of plasma concentrations that are considered to be optimal for treatment are proposed for those drugs, for which the evaluation of the literature demonstrated strong evidence. Moreover, situations are defined when pharmacogenetic (phenotyping or genotyping) tests are informative in addition to TDM. Finally, practical instructions are given how to use TDM. They consider preparation of TDM, analytical procedures, reporting and interpretation of results and the use of information for patient treatment. Using the consensus guideline will help to ensure optimal clinical benefit of TDM in psychiatry.
Electroless plating of magnetic materials on catalytically active noble metal seeds is a powerful tool to design highly efficient recyclable catalysts. For the electroless plating procedure of ...metallic nanotubes in porous polymer templates, a sensitisation and activation process of the template is necessary. Therefore, metallic seeds are created on the surface of the polymer, which then enable the selective heterogeneous nucleation of a metal film on the template's surface. By choosing the metals for seeds and structures wisely, different functional materials can be purposefully combined. In this work magnetically recoverable catalysts were designed, which consist of magnetic NiCo nanotubes as carrier for catalytically active Pd seeds. The synthesised catalyst structures were thoroughly characterised by SEM, TEM, EDX, XRD, XPS, ICP-OES, VSM and then tested in the 4-nitrophenol reduction reaction, which was monitored by UV-Vis spectroscopy. After the reaction the structures were recycled and reused without a decrease in activity.
One of the grand challenges in glacier research is to assess the total ice volume and its global distribution. Over the past few decades the compilation of a world glacier inventory has been ...well-advanced both in institutional set-up and in spatial coverage. The inventory is restricted to glacier surface observations. However, although thickness has been observed on many glaciers and ice caps around the globe, it has not yet been published in the shape of a readily available database. Here, we present a standardized database of glacier thickness observations compiled by an extensive literature review and from airborne data extracted from NASA's Operation IceBridge. This database contains ice thickness observations from roughly 1100 glaciers and ice caps including 550 glacier-wide estimates and 750,000 point observations. A comparison of these observational ice thicknesses with results from area- and slope-dependent approaches reveals large deviations both from the observations and between different estimation approaches. For glaciers and ice caps all estimation approaches show a tendency to overestimation. For glaciers the median relative absolute deviation lies around 30% when analyzing the different estimation approaches. This initial database of glacier and ice caps thickness will hopefully be further enlarged and intensively used for a better understanding of the global glacier ice volume and its distribution.
•First standardized GLAcier THIckness DAtabase (GlaThiDa)•Compilation of ice thickness observations from roughly 1100 glaciers and ice caps•Including 550 glacier-wide estimates and 750,000 point observations•Assessment by comparison with area- and slope-dependent estimation approaches
: We want to call attention to a mint plant, called diviner's sage ( Salvia divinorum), originally used in shamanic ceremonies of the Mazatec Indians of Mexico. On numerous websites of the internet, ...this ancient herbal drug and its extracts are offered as a legal means of widening individual awareness. Regarding its dose-response relationship, the active ingredient, salvinorin A, is one of the most potent naturally occurring hallucinogens. Laws on controlled substances, except for Finland, Denmark and Australia, do not prohibit cultivating, consuming or dealing with Salvia divinorum. Ingestion by smoking, vaporising or chewing, induces a short-lived inebriant state with intense, bizarre feelings of depersonalization. This article wants to be a signal for physicians or psychotherapists to take Salvia into consideration, when exploring young people for drug use.
We report the individual perceptions of a young man consuming Salvia divinorum. We review the scarce scientific literature and consider relevant internet websites.
We define open issues for further investigations and try to discuss why Salvia divinorum may be of interest for teenagers and young adults in Europe.
The pharmacotherapy of 61 suicide victims (0.24 % of 27,078 admissions from January 1, 1980 to December 31, 1999) was compared to that of a control group matched for age, gender and diagnosis at the ...time of discharge.
Both groups were also comparable regarding stay in hospital, history of psychiatric disease, and frequency of hospitalisations during the year preceding the index evaluation. Multiple but not single suicide attempts were significantly more frequent in patients who were later to complete the suicide than in controls. Schizophrenia (ICD-9, ICD-10) was the most frequent diagnosis among suicide victims (44.3 %). Affective psychosis (ICD-9, ICD-10) bore the highest relative risk (0.8 %). 50 % of the schizophrenic patients in the suicide group had been continuously treated with full-dose tricyclic antidepressants. The CPZ-equivalents in the patients treated with antipsychotics were not of discriminating value. Four of 27 schizophrenic patients in the suicide group had been off neuroleptics for ten days or more; this was never observed among the controls. Lorazepam applied in 40% of the schizophrenic and in 25 % of the affective psychosis suicide victims had more often been withdrawn or reduced during the ten days preceding suicide than among controls. No schizophrenic suicide victims but five controls had been on mood stabilisers. The use of antipsychotics (classical and atypical) and a recent change in tricyclic drug or drug dose were more frequent in suicide victims with affective psychosis. Lithium had been given to one patient, but it had also been administered to six controls; this difference is significant.
Mood stabilisers, especially lithium, should be considered more often in patients with previous suicide attempt(s). When changing antidepressants in affective psychosis, benzodiazepines might be given more deliberate consideration. Patients in all diagnostic categories should be closely guided by means of intensified psychotherapeutic interventions while undergoing a benzodiazepine reduction. The treatment of patients suffering from schizophrenia with full-dose tricyclic regimens should be considered as possibly enhancing the acute suicide risk in some individuals.
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 the UKU side-effect scale. 84 patients with depressive disorder according to DSM-IV were recruited in three centers (TDM, n = 43; no-TDM, n = 41; mean age 49.9 +/- 13.2 years, 63.1 % female). Patients were treated with either amitriptyline (n = 69) or doxepin (n = 15); the mean dosage at endpoint was 126 +/- 35 mg and 155 +/- 47 mg, respectively. The mean study duration was 21 +/- 8 days. Both groups improved according to HAMD (from 25.2 +/- 8.4 at baseline to 12.0 +/- 7.4 at endpoint) and CGI scores (68 % responders). Moderately severe or severe side effects occurred in 16 % of patients. Adequate dose adjustment was significantly higher in the TDM group (60 % vs. 46 %, p < 0.05); this led to a significantly higher rate of therapeutic serum levels in the TDM group (58 % vs. 44 %, p < 0.05). Direct effects of TDM were not found for effectiveness. Therapeutic TCA serum levels over weeks one to three, however, were associated with significantly better outcome at endpoint (p < 0.05) as measured with changes in the HAMD or CGI response rates from baseline to endpoint. Finally, considerable side effects occurred significantly more often when serum levels were above the therapeutic range (27 % vs. 11 %; p < 0.01). We conclude that treating depression with TCA can be optimized by early TDM, which is superior to clinical judgment on its own. Since the psychiatrists in charge were less than completely "compliant" to the recommendations provided together with serum levels, the effect could be more pronounced than this study shows. The results encourage further studies in order to optimize antidepressant pharmacotherapy when using TDM appropriately.
Neuropeptide Y (NPY) modulates ethanol drinking in rodents. The C-allele of the T1128C polymorphism of the human NPY gene has been previously associated with elevated alcohol consumption in a Finn ...population study. The present study tested the hypothesis that the T1128C polymorphism is associated with the diagnosis of alcoholism or with severe forms of alcohol withdrawal and with the daily consumption of alcohol in alcoholic patients. After PCR-RFLP genotyping, two groups of alcoholics with severe withdrawal symptoms (delirium tremens, n = 83; withdrawal seizures, n = 65) were compared to alcoholics with mild withdrawal symptoms (n = 97). An elevated frequency of the C-allele in the individuals with severe withdrawal symptoms was found, however not reaching statistical significance. Further a group of healthy controls (n = 102) was compared to all included alcoholics (n = 216) revealing no significant result. Alcoholics carrying the C-allele reported a non significantly elevated daily consumption of alcohol compared to alcoholics with the TT genotype. All alcohol dependent subjects with severe withdrawal symptoms revealed a significantly elevated daily consumption of alcohol compared to alcoholics with only mild withdrawal symptoms. More studies on different ethnic groups are needed to further elucidate the influence of the NPY gene on alcoholism.
TDM of psychotropic drugs is widely used, but there is little consensus regarding its optimal use in the clinical context. This prompted a multidisciplinary group comprised of clinical biochemists, ...clinical pharmacologists, and psychiatrists of the AGNP (Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie) to provide a consensus guideline. This will allow clinical psychiatrists, practitioners, and laboratory directors involved in psychopharmacotherapy to optimize TDM of antidepressants, antipsychotics, and opioid substituents. Recommendations are also given on the combined use of TDM and pharmacogenetic tests.
Drug monitoring in psychiatry usually serves psychoactive drug plasma concentration measurement. Anticholinergic properties offer a faster approach to monitoring pharmacodynamic intraindividual ...effects of the drug by measuring their effects on heart rate variability (HRV), which is sympathetically and parasympathetically controlled via cholinergic synapses. The plasma concentrations of the atypical antipsychotics clozapine and olanzapine correlated with parameters of HRV in 59 patients suffering from schizophrenia or schizoaffective disorder. HRV during 4 minutes at rest was extracted from the ECG trace of a routine digital EEG registration in addition to blood sampling for plasma concentration measurement (HPLC method). We calculated sympathetically and parasympathetically controlled heart frequency bands (low, medium and high frequency) and other HRV parameters, coefficient of variation (CV), and root mean square of successive differences (RMSSD). All HRV parameters were significantly more impaired in clozapine patients (n = 33, mean clozapine plasma concentration 331 +/- 294 ng/ml) than in olanzapine patients (n = 26, mean olanzapine plasma concentration 42 +/- 32 ng/ml) and demonstrated 1.7 - 4.8 times the cardiac anticholinergic properties of clozapine in vivo. 14 out of 14 patients with a CV beyond 3.2 % had clozapine plasma concentrations below the proposed optimal therapeutic concentration of 350 ng/ml. All HRV parameters were inversely and significantly correlated with the clozapine plasma concentrations (such as lgCV: r = - 0.73, p < 0.001) and, to a lesser extent, with the olanzapine plasma concentrations (lgCV r = - 0.44, p < 0.05). These results underline the potential clinical value of HRV parameter extraction from routine ECGs in predicting plasma concentrations and objective individual neurocardiac effects of drugs with anticholinergic properties.
In contrast to several authors who found hepatic cytochrome P 450 2D6 (CYP2D6) metabolising status to be clinically unimportant in treatment with the CYP2D6 substrate, risperidone, we report on a ...17-year-old schizophrenic patient who suffered from severe extrapyramidal side effects (EPS) while being treated with risperidone at 4 mg per day. He was genotyped as a CYP2D6 poor metaboliser (PM). The active moiety of risperidone (sum of risperidone and 9-hydroxyrisperidone) was elevated and increased even further under co-medication with haloperidol and biperiden. We conclude that the PM phenotype for CYP2D6 of this patient had major clinical importance in treatment with risperidone. Most likely metabolic pathways other than CYP2D6 were also involved that are probably inhibited by haloperidol.
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