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Real-world and clinical trial data support that clozapine is the only effective antipsychotic for treatment resistant schizophrenia and other severe mental illnesses. Clozapine also reduces rates of suicidality, psychiatric hospitalization and all-cause mortality. However, clozapine is underutilized for two reasons: misunderstandings of its efficacy benefits and misapprehension of, limited knowledge or misinformation about the management of treatment related risks and adverse effects. In response to worldwide efforts to promote clozapine use, this user-friendly Handbook provides clinicians with evidence-based approaches for patient management, as well as logical approaches to the management of clinical situations and adverse effects. It outlines clearly the rationale for specific management decisions and prioritises the options based on this logic. This Handbook is designed for use by clinicians worldwide and is essential reading for all mental health care professionals.

Clozapine --- Antipsychotic Agents --- Schizophrenia --- administration & dosage --- therapeutic use --- adverse effects --- drug therapy --- Neuroleptiques --- Schizophrénie --- Effets secondaires. --- Thérapeutique. --- Modes d'administration. --- Chimiothérapie. --- Clozapine - administration & dosage --- Clozapine - therapeutic use --- Clozapine - adverse effects --- Schizophrenia - drug therapy --- Antipsychotic Agents. --- administration & dosage. --- therapeutic use. --- adverse effects. --- drug therapy. --- Modes d'administration --- Schizophrénie --- Thérapeutique. --- Chimiothérapie. --- Clozapine.

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Polypharmacy is a necessary and important aspect of drug treatment; however, it becomes a challenge when the medication risks outweigh the benefits for an individual patient. Drug–drug interactions and the introduction of prescribing cascades are common features of polypharmacy, which can lead to ineffectiveness and increased risk of adverse drug reactions (ADR). Genes encoding CYP450 isozymes and other drug-related biomarkers have attracted considerable attention as targets for pharmacogenetic (PGx) testing due to their impact on drug metabolism and response. This Special Issue is devoted to explore the status and initiatives taken to circumvent ineffectiveness and to improve medication safety for polypharmacy patients. Specific areas include drug–drug interactions and consequences thereof in therapeutic management, including PK- and PD-profiling; the application of PGx-based guidance and/or decision tools for drug–gene and drug–drug gene interactions; medication reviews; development and application of deprescribing tools; and drivers and barriers to overcome for successful implementation in the healthcare system.

Medicine --- Pharmaceutical industries --- acute kidney injury --- early biomarker --- plasma neutrophil gelatinase-associated lipocalin --- soluble urokinase plasminogen activator receptor --- medication optimization --- older patients --- emergency department --- multimorbidity --- polypharmacy --- potentially inappropriate medication use --- older adults --- prevalence --- determinants --- chronic --- outpatient --- 2019 Beers criteria --- Ethiopia --- pharmacogenomics --- persons with diabetes --- drug–drug interactions --- drug–gene interactions --- cytochrome P450 --- SLCO1B1 --- drug interaction checkers --- adverse drug reactions --- pharmacogenetics --- personalized medicine --- phenprocoumon --- DOACs --- bleeding --- thromboembolism --- HLA --- drug hypersensitivity --- abacavir --- allopurinol --- flucloxacillin --- antiepileptic drugs --- cost-effectiveness --- shared medication record --- medication reconciliation --- drug information service --- hospital pharmacy service --- electronic prescribing --- electronic medical record --- clinical pharmacist --- CYP2D6 --- CYP2D7P --- CYP2D8P --- copy number variation --- CNV --- genotyping --- 5’nuclease assay --- HRM --- high resolution melting --- drug metabolization --- extracellular vesicles --- exosomes --- microvesicles --- pharmacogene expression --- medication review --- deprescriptions --- quality of life --- aged --- aged, 80 and over --- nursing homes --- deprescribing --- medication-based risk score --- health outcomes --- cytochromes --- CYP1A2 --- adverse drug reaction --- antipsychotics --- olanzapine --- clozapine --- loxapine --- children --- youth --- digital decision-support --- health services research --- general practice --- process evaluation --- antidepressants --- utility --- population-based --- appropriateness --- medication adherence --- digital health