Therapeutic drug monitoring of psychotropic drugs. TDM "nouveau".

TDM applied in psychiatry dates back several decades. The reason for this is that, after the advent of modern clinical psychopharmacology around the middle of the past century, an insight came to common knowledge about the existence of (1) a large interindividual pharmacokinetic (PK) variability for virtually all psychoactive drugs and (2) a worse clinical efficacy not only in inadequate drug concentrations but also in excessively high concentrations. From this concept, the definition of a therapeutic concentration "window" was evidenced for a substantial number of, primarily, antidepressant drugs. However, with the further extensive development of the clinically available pharmacopoeia of psychoactive drugs from the later 1980s until today, the concept of less toxic compounds than before has commonly been launched in the marketing strategies for these newer drugs. This concept also led to the idea that TDM was no longer necessary for the newer types of psychoactive drugs, a position backed up by difficulties in unraveling concentration-effect relationships generally for these drugs in clinical trials. The present survey summarizes the background history for TDM in psychiatry and makes a critical appraisal of why a "lack" of definition of concentration-effect relationships for newer psychoactive drugs is now common. This survey also provides the reader with a novel concept challenging ambient TDM strategies (referred to as TDM "traditionelle") in psychiatry by forwarding a theoretical model called TDM "nouveau." In this model both inter- and intraindividual (over time) PK variation is suggested to be used for dose optimization by TDM in a naturalistic clinical setting. The previous concept of a simple, common concentration "window" existing for all such drugs is questioned by promotion of the use of available PK data merely as "guiding principles" rather than as "reference values" when interpreting the TDM outcome in individual cases.