Developing Functional Routines for TDM and Pharmacogenetic Tests in Psychiatry

In the Department of Clinical Pharmacology at St. Olav's Hospital in Trondheim, Norway there has been a steady increase in the number of TDM analyses performed the past ten years, increasing from approximately 10.000 in 1995 to more than 70.000 in 2003. Drugs used for psychiatric disorders, e.g. newer antidepressants and atypical antipsychotics, accounts for a substantial part of this increase.

In the same period of time the number of TDM analyses has been largely outnumbered by an enormous increase in the number of screening analyses for drugs of abuse (DOA). The increase in the number of DOA analyses has mainly been due to the introduction of DOA screening with LC-MS and the establishment of a large methadone substitution program. The increased workload has made it necessary to raise both the number of employees (from 15 in 1995 to 95 in 2004) and the number of instruments to a total of 34 LC-MS, 3 ion-trap-MS and 10 GC-MS in 2004.

The pharmacological part of the treatment of psychiatric disorders has been and still is a complex and difficult task. The over all result is the sum of individual and environmental factors. Many of these factors are quite difficult to control purely on clinical information. The basic idea was therefore to bring TDM away from a focus on therapeutic ranges and adverse reactions to a focus on TDM as a tool for quality control of the pharmacological part of the treatment. An important part of this focus change was to implement „new“ applications for TDM into the daily practice of the clinicians. Examples of these „new applications“ are use of TDM in verifying compliance, by differentiating the real non-responders from the non-compliant ones, use of TDM in documentation in off-licensed dosing, in off-licensed indications and in questions with medico-legal aspects and in selected „special“ patient groups.

Several cases also clearly demonstrate the potential of TDM as a tool for generating new knowledge, e.g. knowledge about possible drug-drug interactions. These examples must at least be considered as major contributors to hypothesis generation for research.

A critical success factor in the process has been to improve the cooperation with the clinical specialties. Recruiting one specialist in psychiatry and one specialist in general practice, who also have worked in psychiatry, has been very successful. As a consequence of this closer relationship to the clinicians we have started a new approach in the way we are communicating with them by expanding TDM to what we call TEDM, therapeutic and educational drug monitoring. In TEDM we can process new information and knowledge about the drugs (e.g. drug-drug interactions, adverse drug reactions, use in elderly) in a way that our responses may become a platform for both clinicians and patient for improving the pharmacological part of the treatment.

In our department TDM and pharmacogenetics service have been organized in a tight collaboration. Since most of our pharmacogenetic samples are phenotyped by TDM before genotyping, the diagnosis of genetic abnormality is made both easier and more effective. The pharmacogenetic service is provided in collaboration with the department of Medical Genetics. By September 01, 2004 genotyping of the following enzymes are possible: CYP2D6, CYP2C9, CYP2C19, DRD2 and DRD3 (dopamine receptor mutations) and NAT-2.

Serotonin and dopamine receptors and serotonin transporter genetics are under development.

We conclude that TEDM is a useful tool to increase the quality of pharmacotherapy and an important tool in correcting for pharmacokinetic variability. We also mean that pharmacogenetic testing can add explanation to this variability. But most important TEDM and pharmacogenetics should only be tools in clinical decision-making, and not the steering wheel.