How to Determine a Therapeutic Reference Range for a Psychotropic Drug Systematically? Recommendations of the TDM Task Force of the AGNP.

Background: Therapeutic drug monitoring (TDM) is essential for controlling pharmacogenetic and pharmacokinetic variations and for optimizing pharmacotherapy. However, its value is often underestimated because of nonsystematic recommendations for target ranges in the literature. The purpose of this study was to emphasize transparency and systematization in the forthcoming Updates to the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP)-TDM Consensus Guidelines.

Mirtazapine blood levels and antidepressant response.

Objective: Therapeutic drug monitoring (TDM) is an important tool for treatment optimisation. Its usefulness has recently been demonstrated for some first-line antidepressants; however, few studies have been reported on the relationship between blood levels of mirtazapine and its antidepressant effects. The aim of this study was to investigate the association between blood concentration of mirtazapine and antidepressant response.

Optimisation of pharmacotherapy in psychiatry through therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests: Focus on antipsychotics.

Background: For psychotic disorders (i.e. schizophrenia), pharmacotherapy plays a key role in controlling acute and long-term symptoms.

Unraveling the Influence of Age, IQ, Education, and Negative Symptoms on Neurocognitive Performance in Schizophrenia: A Conditional Inference Tree Analysis.

Introduction: The complex nature of neurocognitive impairment in schizophrenia has been discussed in light of the mixed effects of antipsychotic drugs, psychotic symptoms, dopamine D receptor blockade, and intelligence quotient (IQ). These factors have not been thoroughly examined before.

Methods: This study conducted a comprehensive re-analysis of the CATIE data using machine learning techniques, in particular Conditional Inference Tree (CTREE) analysis, to investigate associations between neurocognitive functions and moderating factors such as estimated trough dopamine D receptor blockade with risperidone, olanzapine, or ziprasidone, Positive and Negative Syndrome Scale (PANSS), and baseline IQ in 573 patients with schizophrenia.

Update Lessons from PET Imaging Part II: A Systematic Critical Review on Therapeutic Plasma Concentrations of Antidepressants.

Background: Compared with antipsychotics, the relationship between antidepressant blood (plasma or serum) concentrations and target engagement is less well-established.

Methods: We have discussed the literature on the relationship between plasma concentrations of antidepressant drugs and their target occupancy. Antidepressants reviewed in this work are citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, duloxetine, milnacipran, tricyclic antidepressants (amitriptyline, nortriptyline, and clomipramine), bupropion, tranylcypromine, moclobemide, and vortioxetine.

Update Lessons from Positron Emission Tomography Imaging Part I: A Systematic Critical Review on Therapeutic Plasma Concentrations of Antipsychotics.

Background: Positron emission tomography (PET) and single photon emission tomography (SPECT) of molecular drug targets (neuroreceptors and transporters) provide essential information for therapeutic drug monitoring-guided antipsychotic drug therapy. The optimal therapeutic windows for D 2 antagonists and partial agonists, as well as their proposed target ranges, are discussed based on an up-to-date literature search.

Methods: This part I of II presents an overview of molecular neuroimaging studies in humans and primates involving the target engagement of amisulpride, haloperidol, clozapine, aripiprazole, olanzapine, quetiapine, risperidone, cariprazine, and ziprasidone.

Therapeutic Reference Range for Olanzapine in Schizophrenia: Systematic Review on Blood Concentrations, Clinical Effects, and Dopamine Receptor Occupancy.

Aiming at revising the therapeutic reference range for olanzapine, the present study highlights the association between blood olanzapine levels, clinical effects, and dopamine D-receptor occupancy for oral and long-acting injectable (LAI) formulations. Databases were systematically searched for randomized controlled trials (RCTs) and uncontrolled trials concerning blood olanzapine levels in relation to clinical outcomes or D-receptor occupancy using MEDLINE (PubMed), Web of Science, PsycINFO, and Cochrane Library (March 2021, updated in December 2021). We excluded articles not written in English or German and non-human data.

Low Escitalopram Concentrations in Patients with Depression predict Treatment Failure: A Naturalistic Retrospective Study.

Introduction: Cross sectional therapeutic drug monitoring (TDM) data mining introduces new opportunities for the investigation of medication treatment effects to find optimal therapeutic windows. Medication discontinuation has been proven useful as an objective surrogate marker to assess treatment failure. This study aimed to investigate the treatment effects of escitalopram and pharmacokinetic influences on blood levels using retrospectively assessed data from a TDM database.

Behind the Curtain: Therapeutic Drug Monitoring of Psychotropic Drugs from a Laboratory Analytical Perspective.

Purpose: Therapeutic drug monitoring (TDM) is a well-established tool for guiding psychopharmacotherapy and improving patient care. Despite their established roles in the prescription of psychotropic drugs, the "behind the curtain" processes of TDM requests are invariably obscure to clinicians, and literature addressing this topic is scarce.

Methods: In the present narrative review, we provide a comprehensive overview of the various steps, starting from requesting TDM to interpreting TDM findings, in routine clinical practice.

Therapeutic Reference Range for Aripiprazole in Schizophrenia Revised: a Systematic Review and Metaanalysis.

Rationale: While one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood levels is questioned by many clinicians. This is due to the often-missing validation of therapeutic reference ranges.

Objectives: Here, we present a prototypical meta-analysis of the relationships between blood levels of aripiprazole, its target engagement in the human brain, and clinical effects and side effects in patients with schizophrenia and related disorders.

Molecular Imaging of Dopamine Partial Agonists in Humans: Implications for Clinical Practice.

Positron emission tomography (PET) has been used since the late 1980s for the assessment of relationships between occupancy of D receptors by antipsychotic drugs in the human brain and the clinical effects and side effects of these compounds in patients. It is now well established for most D antagonists, both of the first and the second generation, that the ideal occupancy of their target receptors is between approximately 65 and 80%. If the occupancy is below 65%, the probability of treatment response is reduced, if the occupancy is higher than 80%, the risk for extrapyramidal side-effects increases substantially.

Is Therapeutic Drug Monitoring Relevant for Antidepressant Drug Therapy? Implications From a Systematic Review and Meta-Analysis With Focus on Moderating Factors.

Unlabelled: Inter-individual differences in antidepressant drug concentrations attained in blood may limit the efficacy of pharmacological treatment of depressive disorders. Therapeutic drug monitoring (TDM) enables to determine drug concentrations in blood and adjust antidepressant dosage accordingly. However, research on the underlying assumption of TDM, association between concentration and clinical effect, has yielded ambiguous results for antidepressants.

Antidepressant efficacy is correlated with plasma levels: mega-analysis and further evidence.

The debate around optimal target dose for first-line antidepressants (ADs) is still ongoing. Along this line, therapeutic drug monitoring (TDM) represents one of the most promising tools to improve clinical outcome. Nevertheless, a few data exist regarding the concentration-effect relationship of first-line ADs which limits TDM implementation in routine clinical practice.

Therapeutic Reference Ranges for Psychotropic Drugs: A Protocol for Systematic Reviews.

For many psychotropic drugs, monitoring of drug concentrations in the blood (Therapeutic Drug Monitoring; TDM) has been proven useful to individualize treatments and optimize drug effects. Clinicians hereby compare individual drug concentrations to population-based reference ranges for a titration of prescribed doses. Thus, established reference ranges are pre-requisite for TDM.

Therapeutic Drug Monitoring of Long-Acting Injectable Antipsychotic Drugs.

Background: The use of therapeutic drug monitoring (TDM) to guide treatment with long-acting injectable (LAI) antipsychotics, which are increasingly prescribed, remains a matter of debate. The aim of this review was to provide a practical framework for the integration of TDM when switching from an oral formulation to the LAI counterpart, and in maintenance treatment.

Methods: The authors critically reviewed 3 types of data: (1) positron emission tomography data evaluating dopamine (D2/D3) receptor occupancy related to antipsychotic concentrations in serum or plasma; D2/D3 receptors are embraced as target sites in the brain for antipsychotic efficacy and tolerability, (2) pharmacokinetic studies evaluating the switch from oral to LAI antipsychotics, and (3) pharmacokinetic data for LAI formulations.