Therapeutic Drug Monitoring and its implications on acute and long-term treatment with neuroleptics

Abstract

Therapeutic Drug Monitoring (TDM) is a useful tool to survey individual patients for the correct prescription and dosing of neuroleptic drugs. Confounders for causal drug effect relations are both patient-related and drug-related. An example of a patient-related confounders is problems with compliance to prescribed medication that can be objectively identified or ruled out by TDM in cases of non-response or partial but insufficient clinical response. This problem may arise both in the acute phase of treatment as well as during long-term treatment. Examples of combined patient-related and drug-related confounders are the very individual pharmacokinetic (PK) handling of the drug once the patent has ingested a neuroleptic compound. All such drugs undergo significant metabolism in the body, which is subjected to major inter-individual variability to a large extent due to existence of polymorphic genetic expressions among enzymes responsible for drug detoxification processes in the liver. Moreover, each separate neuroleptic compound, whether its is a classical or an atypical agent, has different affinities for these drug catabolic enzymes. The entire picture of PK-variability existing for antipsychotic drugs is therefore in healthy young male volunteers about one order of magnitude. In real life, i.e. in the everyday naturalistic clinical setting where for example also polypharmacy is a common feature, this variation in the PK between individuals increase 10-fold to be about two orders in magnitude.

This presentation focus TDM-studies where PK-variability and drug PK-effect relations for traditional as well as atypical antipsychotic agents are scrutinized.