Personalized treatment with psychiatric drugs through Pharmacogenetics and Therapeutic Drug Monitoring: optimizing individual treatment using therapeutic drug monitoring of clozapine and pharmacogenetics

Millions of people worldwide are treated with psychopharmaceuticals for diseases such as depression, bipolar disorder or schizophrenia. However, in many cases the effectiveness of these drugs is suboptimal; in many patients, complete reduction of their symptoms is not achieved. Treated with equal dosages of the same drug, there appear to be large differences between patients in their therapeutic response and in the occurrence of side effects.
By focusing on the characteristics of the individual patient, rather than the overall population, the treatment of individual patients can be optimized. The focus here is on clinical, genetic and environmental differences between patients that may affect drug efficacy and tolerability.


The first part of this thesis focuses on microsampling techniques. This are techniques in which drug concentrations can be determined in only a few drops of sample. These samples can be collected by finger prick for example instead of venous blood sampling. This makes performing therapeutic drug monitoring in daily practice easier and more patient-friendly.
The second part looks at genetic differences of two enzymes; P-glycoprotein and CYP17. P-glycoprotein is involved in the transport of psychopharmaceuticals in the blood-brain barrier back into the bloodstream so that they cannot penetrate the brain. The influence of differences in the gene encoding P-glycoprotein on the effectiveness of psychopharmaceuticals and on the risk of side effects has been studied. Genetic differences don’t seem to influence the overall response rate but might influence the speed of response.