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

Abstract

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.

Elevated Clozapine Blood Concentrations After Second COVID-19 Vaccination With Spikevax (COVID-19 Vaccine Moderna)

“…Clozapine blood concentrations are highly sensitive to inflammation-related inhibition of especially CYP1A2 activity, 4,17 but the underlying multifactorial mechanisms are incompletely understood. A vaccination-induced activation of proinflammatory cytokines and after impairment of hepatic CYP450 synthesis may be a reason of the increased serum levels, but alterations of drug transporters and other drug-metabolizing enzymes could have been affected with corresponding consequences for drug metabolism and excretion 6,11,18,19 .…”

Monitoring of the Antipsychotic Therapy Effectiveness

“…Установлено, что продукция цитокинов IL-1β, IL-6, IL-8, IL-10, IL-12, IL-15, IL-18 увеличивается у больных шизофренией [37]. С другой стороны, АП вызывают иммуносупрессию путем стимуляции интерлейкинов IL-10 или IL-1RA или ингибирования цитокинов [38].…”

COVID-19-Impfung unter Psychopharmakotherapie

“…Diese Kaskade betrifft unter anderem Clozapin, welches überwiegend über CYP1A2 verstoffwechselt wird, dessen Serumkonzentration im Rahmen immunvermittelter Prozesse massiv bis auf toxische Spiegel mit entsprechender klinischer Symptomatik ansteigen kann [39]. Ein aktueller Bericht schildert den Fall eines 51-jährigen aufgrund einer schizoaffektiven Störung mit Clozapin behandelten Patienten, der 4 Tage nach der Impfung mit dem mRNA-Impfstoff BNT162b2 von BioN-Tech/Pfizer ein Delir mit mehrfachen Sturzereignissen entwickelte.…”