[Understanding and assessing the antidepressant drug-associated risk of bleeding]. / Das Blutungsrisiko unter Antidepressiva verstehen und einschätzen.

Antidepressants, in particular selective serotonin reuptake inhibitors (SSRIs), are the most commonly prescribed psychopharmacological drug group. Thus, a precise knowledge of the expected adverse drug reactions is indispensable. The increased risk of bleeding events is well documented, especially in patients treated with SSRIs. However, many other antidepressant drug groups have also been implicated in increasing the risk of bleeding. In the following review, the thrombocytic serotonin system and the respective targets of the different antidepressants are explained. Subsequently, the available literature on bleeding under the respective antidepressant classes or individual substances is presented, using data from meta-analyses whenever possible. In addition to the risk of bleeding in general, individual bleeding entities are also considered, such as gastrointestinal and cerebral hemorrhages. Finally, the effects of other drugs that increase the risk of bleeding (i. e., nonsteroidal anti-inflammatory drugs, platelet aggregation inhibitors and anticoagulants) in combination with antidepressant drugs are discussed. The information presented here is meant to guide practitioner's decision making regarding an appropriate antidepressant pharmacotherapy based on the patient's individual risk constellation.

[Vaccination Against COVID-19 in Patients Treated with Psychotropic Drugs]. / COVID-19-Impfung unter Psychopharmakotherapie.

Vaccines against SARS-CoV-2 have been available in the European Union since December 2020. Persons suffering from mental illness have an increased risk of a severe or fatal course following an infection with SARS-CoV-2. Thus, the question arises to what extent interactions between the newly approved vaccines and psychotropic drugs may be expected. Data on the tolerability and efficacy of vaccines against SARS-CoV-2 under treatment with psychotropic drugs are not available to date - however, potential interactions can be derived from previous investigations on vaccines against other pathogens, such as a reduced immune response with lower clinical efficacy and an increase in drug plasma levels due to the indirect vaccine-mediated inhibition of metabolizing enzymes. On the other hand, depressed patients treated with antidepressant medication show a better immune response.

Therapeutic Drug Monitoring of Second- and Third-Generation Antipsychotic Drugs-Influence of Smoking Behavior and Inflammation on Pharmacokinetics.

Both inflammation and smoking can influence a drug's pharmacokinetic properties, i.e., its liberation, absorption, distribution, metabolism, and elimination. Depending on, e.g., pharmacogenetics, these changes may alter treatment response or cause serious adverse drug reactions and are thus of clinical relevance. Antipsychotic drugs, used in the treatment of psychosis and schizophrenia, should be closely monitored due to multiple factors (e.g., the narrow therapeutic window of certain psychotropic drugs, the chronicity of most mental illnesses, and the common occurrence of polypharmacotherapy in psychiatry). Therapeutic drug monitoring (TDM) aids with drug titration by enabling the quantification of patients' drug levels. Recommendations on the use of TDM during treatment with psychotropic drugs are presented in the Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology; however, data on antipsychotic drug levels during inflammation or after changes in smoking behavior-both clinically relevant in psychiatry-that can aid clinical decision making are sparse. The following narrative review provides an overview of relevant literature regarding TDM in psychiatry, particularly in the context of second- and third-generation antipsychotic drugs, inflammation, and smoking behavior. It aims to spread awareness regarding TDM (most pronouncedly of clozapine and olanzapine) as a tool to optimize drug safety and provide patient-tailored treatment.

Guía de consenso de expertos para la monitorización terapéutica de drogas en neuropsicofarmacología / Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology

OBJETIVO: La Monitorización Terapéutica de Drogas (llamada en inglés TDM: therapeutic drug monitoring) combina la cuantificación de las concentraciones de medicamentos en la sangre, la interpretación farmacológica y las directrices de tratamiento. La TDM introduce una herramienta de medicina de precisión en una ípoca de gran conciencia de la necesidad de tratamientos personalizados en neurología y psiquiatría. Las indicaciones claras de la TDM incluyen la ausencia de respuesta clínica en el rango de dosis terapéuticas, la evaluación de la adherencia farmacológica, problemas de tolerancia e interacciones medicamentosas. MÉTODOS: Basándose en la literatura existente, se describieron los rangos de referencia terapéutica recomendables, los valores críticos de laboratorio y los niveles de recomendación para usar la TDM para la optimización de dosis sin indicaciones específicas, se calcularon los factores de conversión, los factores para el cálculo de concentraciones medicamentosas relacionadas con la dosis (en inglés DRC dose-to-ratioconcentration) y el cociente entre el metabolito y el compuesto original (en inglés se llama MPR: metabolite-to-parent ratio). RESULTADOS: Este resumen de las guías actualizadas del consenso por la Task Force del TDM del Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie, ofrece el conocimiento práctico y teórico para la integración de la TDM como parte de la farmacoterapia con medicamentos neuropsiquiátricos en la práctica clínica rutinaria. CONCLUSIONES: La presente traducción en español, de la guía para la aplicación del TDM en medicamentos neuropsiquiátricos, tiene como objetivo ayudar a los clínicos a mejorar la seguridad y la eficacia de los tratamientos

OBJECTIVES: Therapeutic drug monitoring (TDM) combines the quantification of drug concentrations in blood, pharmacological interpretation, and treatment guidance. TDM introduces a precision medicine tool in times of increasing awareness of the need for personalised treatment. In neurology and psychiatry, TDM can guide pharmacotherapy for patient subgroups such as children, adolescents, pregnant women, elderly patients, patients with intellectual disabilities, patients with substance use disorders, individuals with pharmacokinetic peculiarities, and forensic patients. Clear indications for TDM include lack of clinical response in the therapeutic dose range, assessment of drug adherence, tolerability issues, and drug-drug interactions. METHODS: Based upon existing literature, recommended therapeutic reference ranges, laboratory alert levels, and levels of recommendation to use TDM for dosage optimisation without specific indications, conversion factors, factors for calculation of dose-related drug concentrations, and metabolite-to-parent ratios were calculated. RESULTS: This summary of the updated consensus guidelines by the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) offers the practical and theoretical knowledge for the integration of TDM as part of pharmacotherapy with neuro- psychiatric agents into clinical routine. CONCLUSIONS: The present guidelines for TDM application for neuropsychiatric agents aim to assist clinicians in enhancing safety and efficacy of treatment

[Major depression and liver disease: the role of microbiome and inflammation]. / Depressionen und Lebererkrankungen: Die Rolle von Mikrobiom und Inflammation.

Depression and liver disease are closely associated. Every third patient with liver cirrhosis or hepatitis shows depressive symptoms. On the other hand, every third patient with depressive disorder develops an alcohol disorder at some point during his / her life. A crucial link between depression and hepatic disease seems to be inflammatory processes in which the microbiome and increased intestinal permeability of the intestine play a pivotal role. Depression as well as liver disease, alcohol consumption, stress, and aging processes disturb the delicate balance of intestinal microbiota resulting in increased intestinal permeability. Therefore, bacteria or their metabolites such as the endotoxine lipopolysaccharide are able to reach the blood circulation resulting in inflammation in the liver as well as in the brain via a cytokine cascade, which in turn can lead to liver changes, depression, obesity, and metabolic syndrome. Therefore, liver values, blood glucose levels, and metabolic parameters should be closely monitored in patients with depressive disorders, and in the case of patients with hepatic diseases, increased attention should be given to depressive symptoms, diabetes and obesity.

Psychopharmacology in transplantation medicine.

Organ transplantation has become a well-established treatment option in patients with end-stage organ diseases. Although quality of life has markedly improved, psychiatric disorders before and after transplantation are more frequent compared to the general population. Psychopharmacological treatment is recommended for almost all mental disorders according to current guidelines, but may pose particular problems in organ transplant patients. Changes in the metabolism and elimination of drugs during organ insufficiency, drug interactions, and overlapping side effects between psychopharmacological and immunosuppressive drugs are challenging problems in clinical management. Furthermore, questions frequently arise concerning the use of psychopharmacological treatment options for sleeping and anxiety disorders. This article reviews psychopharmacology in organ transplant patients, with particular attention to frequent psychiatric disorders observed in the disease course of end-stage organ diseases.

[Therapeutic drug monitoring in neuropsychopharmacology : Summary of the consensus guidelines 2017 of the TDM task force of the AGNP]. / Therapeutisches Drug-Monitoring in der Neuropsychopharmakologie : Zusammenfassung der Konsensusleitlinien 2017 der TDM-Arbeitsgruppe der AGNP.

Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood serum or plasma to optimize pharmacological therapy. TDM is an instrument with which the high interindividual variability of pharmacokinetics of patients can be identified and therefore enables a personalized pharmacotherapy. In September 2017 the TDM task force of the Working Group for Neuropsychopharmacology and Pharmacopsychiatry (AGNP) published an update of the consensus guidelines on TDM published in 2011. This article summarizes the essential statements for the clinical practice in psychiatry and neurology.

TDM in psychiatry and neurology: A comprehensive summary of the consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology, update 2017; a tool for clinicians.

OBJECTIVES: Therapeutic drug monitoring (TDM) combines the quantification of drug concentrations in blood, pharmacological interpretation and treatment guidance. TDM introduces a precision medicine tool in times of increasing awareness of the need for personalized treatment. In neurology and psychiatry, TDM can guide pharmacotherapy for patient subgroups such as children, adolescents, pregnant women, elderly patients, patients with intellectual disabilities, patients with substance use disorders, individuals with pharmacokinetic peculiarities and forensic patients. Clear indications for TDM include lack of clinical response in the therapeutic dose range, assessment of drug adherence, tolerability issues and drug-drug interactions. METHODS: Based upon existing literature, recommended therapeutic reference ranges, laboratory alert levels, and levels of recommendation to use TDM for dosage optimization without specific indications, conversion factors, factors for calculation of dose-related drug concentrations and metabolite-to-parent ratios were calculated. RESULTS: This summary of the updated consensus guidelines by the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie offers the practical and theoretical knowledge for the integration of TDM as part of pharmacotherapy with neuropsychiatric agents into clinical routine. CONCLUSIONS: The present guidelines for TDM application for neuropsychiatric agents aim to assist clinicians in enhancing safety and efficacy of treatment.

Absence of pharmacokinetic interaction between roflumilast and digoxin in healthy adults.

Numerous interactions are known for digoxin, which is a drug with a narrow therapeutic index and a substrate of P-glycoprotein (P-gp). This study investigated potential effects of coadministration on pharmacokinetics and safety of both drugs when a single dose of digoxin was concomitantly administered with roflumilast under steady-state conditions. Sixteen healthy male and female adults were randomly assigned in an open-label, crossover study to either of 2 treatment sequences that consisted of 2 treatment periods separated by a washout phase. Treatments were oral daily doses of roflumilast for 14 days given concomitantly on days 1 and 14 with a single oral dose of digoxin or an oral dose of digoxin once on day 1. Plasma samples for pharmacokinetic evaluations of digoxin and roflumilast concentrations with and without concomitant treatment were taken. The rate of digoxin absorption was slightly (15%) but statistically insignificantly increased, whereas the extent of absorption was not altered by concomitant medication with roflumilast. Concomitant medication with digoxin did not significantly affect steady-state pharmacokinetics of either roflumilast or its active metabolite roflumilast N-oxide. Roflumilast is not an inhibitor of P-gp. No safety or tolerability concerns were detected with coadministration of roflumilast and digoxin.

Clozapine case series.

Clozapine is not a drug that is ever used casually. Patients generally are afflicted with severe illnesses and have demonstrated treatment resistance and/or intolerance to other therapeutic options before clozapine is seriously considered. When the clinical stakes are this high, it is especially important that physicians gain an appreciation for the various drug-drug interactions that can significantly increase or decrease clozapine blood levels; such pharmacokinetic changes can derail clozapine treatment by producing clozapine toxicity or loss of antipsychotic efficacy, respectively. The authors present a case series of five drug-drug interactions involving clozapine, each of which illustrates different mechanisms by which the metabolism of clozapine can be altered. Exploring these cases should help clinicians anticipate and avoid these undesirable drug-drug interactions.

The AGNP-TDM Expert Group Consensus Guidelines: focus on therapeutic monitoring of antidepressants.

Therapeutic drug monitoring (TDM) of psychotropic drugs such as antidepressants has been widely introduced for optimization of pharmacotherapy in psychiatric patients. The interdisciplinary TDM group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has worked out consensus guidelines with the aim of providing psychiatrists and TDM laboratories with a tool to optimize the use of TDM. Five research-based levels of recommendation were defined with regard to routine monitoring of drug plasma concentrations: (i) strongly recommended; (ii) recommended; (iii) useful; (iv) probably useful; and (v) not recommended. In addition, a list of indications that justify the use of TDM is presented, eg, control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic particularity concerning drug metabolism, and children, adolescents, and elderly patients. For some drugs, studies on therapeutic ranges are lacking, but target ranges for clinically relevant plasma concentrations are presented for most drugs, based on pharmacokinetic studies reported in the literature. For many antidepressants, a thorough analysis of the literature on studies dealing with the plasma concentration-clinical effectiveness relationship allowed inclusion of therapeutic ranges of plasma concentrations. In addition, recommendations are made with regard to the combination of pharmacogenetic (phenotyping or genotyping) tests with TDM. Finally, practical instructions are given for the laboratory practitioners and the treating physicians how to use TDM: preparation of TDM, drug analysis, reporting and interpretation of results, and adequate use of information for patient treatment TDM is a complex process that needs optimal interdisciplinary coordination of a procedure implicating patients, treating physicians, clinical pharmacologists, and clinical laboratory specialists. These consensus guidelines should be helpful for optimizing TDM of antidepressants.