Abstract
Therapeutic 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 interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.
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.
In view of the current coronavirus disease 2019 (COVID-19) pandemic, patient care, including that of psychiatric patients, is facing unprecedented challenges. Treatment strategies for mental illness ...include psychotherapy and psychopharmacological interventions. The latter are associated with a multitude of adverse drug reactions (ADR); however, they may currently represent the preferred treatment due to restrictions regarding patient care (i.e. social distancing). Direct contact to patients may have to be reduced in favor of telephone calls or video conferences, so that new techniques in diagnosing and treating patients have to be established to guarantee patient safety. Patients should be extensively informed about relevant ADRs and physicians should actively ask patients about the timely recognition of ADRs. The use of psychotropic drugs may lead to an increased risk of developing ADRs, which are considered to be particularly unfavorable if they occur simultaneously with an acute infection or may even lead to an increased risk of infection. These include respiratory depression, agranulocytosis, intoxication by inhibition of metabolizing enzymes and venous thromboembolism, each of which may be associated with potentially fatal consequences; however, physicians should simultaneously ensure adequate efficacy of treatment, since the ongoing crisis may lead to a worsening of preexisting mental illnesses and to a surge in first onset of psychiatric disorders.
This overview focuses on the aspects of the pharmacotherapy of Parkinson's disease, which is one of the most common disorders of the nervous system. This article presents the complexity of the ...pharmacotherapy of geriatric patients with neurological diseases.
Information about the potential risk factors and aspects of drug safety in the pharmacotherapy of Parkinson's disease.
Selective literature search using PubMed and the scientific-clinical experience of the authors.
Patients with Parkinson's disease are usually geriatric patients with concomitant diseases. As a result they are often treated with comedication which leads to a complex medication regime with more than five drugs. Such polypharmacy increases the risk of adverse drug events due to the rising number of possible interactions and contraindications. To control this risk and maintain a safe therapy, certain measures should be considered. This implies additional need for educational work in order to create awareness regarding potential adverse drug events. In certain cases of diagnosed comorbidities or relevant drug prescriptions in the medication regime, follow-up examinations should be conducted.
Specific parameters of Parkinson's disease, the health-related quality of life of affected patients and the quality of pharmacotherapeutic drug safety can be improved by targeted monitoring of the medication regime. As a result, the overall drug safety can be increased.
In order to understand and quantitatively measure the changing bioavailability that can result from co-medication as well as self-medication and can cause an over-concentration/intoxication or a loss ...of efficacy, Therapeutic Drug Monitoring (TDM) proves to be a very important instrument in researching drug safety.
Based on cases from member clinics of the association Arzneimittelsicherheit in der Psychiatrie (AMSP) and the psychiatric clinic in Kaufbeuren, Germany, that has been equipped with an HPLC system for more than 10 years, it is shown how significantly the relative bioavailability of a substrate (“victim”) can change due to the attack of an inhibitor or an inductor on drug-metabolizing enzymes.
This will be shown with regard to the substrates quetiapine, olanzapine, clozapine, risperidone, carbamazepine (substrate as well as inductive perpetrator), the inhibitors (perpetrators) clarithromycin and erythromycin and the inducers (also perpetrators) carbamazepine and hypericum perforatum. Additionally, the clinical problem of the effects of cytokine release on blood levels of antipsychotics (clozapine, risperidone) during inflammatory processes is discussed. Thereby, blood levels can double with potentially significant clinical effects. Finally, one case is introduced where a poor metabolizer polymorphism of CYP2C19 caused permanent unexpectedly high clozapine levels.
Pharmacokinetics is of great importance for TDM. It can clarify complex relations in the field of polypharmacy and control the risks of multiple medication. Not only psychiatrists and neurologists, but also for example oncologists should be convinced that TDM is a vital instrument for pharmacotherapeutic treatment, which can also be of relevance with regard to liability law.
Zusammenfassung
Im Rahmen der aktuellen
coronavirus disease 2019
(COVID-19)-Pandemie müssen sich viele Bereiche der Medizin umstrukturieren. Dies betrifft auch die Versorgung von Patienten mit ...psychischen Erkrankungen. Die Therapie psychischer Erkrankungen umfasst psychotherapeutische und psychopharmakologische Interventionen. Letztere können mit einer Vielzahl an unerwünschten Arzneimittelwirkungen (UAW) assoziiert sein, stellen aber in der aktuellen Situation mit Kontakt- und Ausgangsbeschränkungen die präferierte Therapieoption dar. Da der direkte Patientenkontakt zugunsten des Telefonats oder der Videokonferenz reduziert ist, müssen angepasste diagnostische und therapeutische Optionen gefunden werden, um eine ausreichende Patientensicherheit zu gewährleisten. Bedeutend sind hierbei die ausführliche Aufklärung der Patienten sowie eine aktive Abfrage von Symptomen zur rechtzeitigen Erkennung von UAW. Unter der Behandlung mit Psychopharmaka sind UAW zu befürchten, die besonders ungünstig sind, wenn sie im Rahmen einer akuten Infektion auftreten oder ein erhöhtes Infektionsrisiko begünstigen. Hierzu gehören Atemdepression, Agranulozytose, Intoxikation durch Hemmung des Arzneistoffmetabolismus und venöse Thromboembolien, die jeweils mit potenziell lebensbedrohlichen Folgen einhergehen. Gleichzeitig sollte auf eine ausreichende Wirksamkeit der Medikation geachtet werden, da die gegenwärtige Krise zu einer Exazerbation vorbestehender psychischer Erkrankungen führen bzw. deren Erstmanifestation begünstigen kann.
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.
PDF
