Therapeutic drug monitoring in neuropsychopharmacology: does it hold its promises?

To produce its characteristic effects, a drug must be present in appropriate concentrations at its sites of action. The latter is not only a function of the dose administered, but also of the extent and rate of drug absorption, distribution, tissue binding, biotransformation, and excretion, which can vary markedly between individual patients due to differences in gender, age, morbidity, smoking or eating habits, differential expression of drug metabolising enzymes or drug transporters or other factors. Therefore drug concentrations in blood resulting after a given dose differ by tenfold or more between individual patients. For psychoactive drugs, animal studies have shown that plasma concentrations of psychotropic drugs correlate well with concentrations in the target organ, the brain. In the brain of patients treated with antipsychotic or antidepressant drugs clear-cut relationships were found between plasma concentrations of the drug and occupancy of dopamine receptors or serotonin uptake sites by positron emission tomography (PET). Monitoring concentrations of psychoactive drugs in plasma of patients, so called therapeutic drug monitoring (TDM), is therefore useful to adjust dosages for optimal "receptor" blockade. TDM is well established for mood stabilizers and anticonvulsant drugs. For other neuropsychiatric drugs, however, "routine" TDM is rare. Optimal target concentrations are unclear for many drugs, and the number of laboratories that use reliable methods to measure the low concentrations of the drugs within a single day is quite limited. Moreover, the use of TDM in practice is far from optimal. The TDM group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP see http://www.agnp.de/) has published literature-based guidelines for optimal use of TDM in psychiatry. TDM can be most informative to solve problems underlying the treatment of an individual patient. It can be clarified if suggested non-compliance or insufficient response in spite of recommended doses is due to rapid metabolism of the drug. Moreover, many drug interactions have been detected by using TDM. In conclusion, TDM is a reliable tool to optimise psychopharmacotherapy. When used adequately it is helpful for many psychiatric patients and in many situations.