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Protein binding of drugs is often mentioned as a subject of importance. In relation to psychotropic drugs it is, however, difficult to find works substantiating the importance in relation to either clinical or pharmacokinetic aspects. One of the reasons for this is probably that most works deal with quantitative rather than qualitative binding measurements. Another reason could be that the many different techniques that have been used have led to different results, and difficulties in establishing the possible clinical significance of such measurements.

The research on pharmacokinetics of tricyclic antidepressants (TCA) has developed in two phases. Through the 1960s the bulk of research was concentrated on qualitative aspects of distribution, metabolism and excretion. By the introduction of methods for drug concentration assay in human blood in the early and mid-1970s, the research has concentrated on quantitative aspects of TCA kinetics and the difficult field of relating clinical pharmacokinetics and pharmacodynamic and therapeutic measurements. In the 1980s a major challenge will be to combine the kinetic/therapeutic relationships to a multiaxial diagnostic system that takes both clinical and biological classification procedures into account. This seems to be the most precise way to improve our diagnostic procedures toward a better identification of those patients that are genuinely responsive to treatment with antidepressants. Further research on factors influencing the kinetics of antidepressants, and kinetic research on the newer antidepressants, is also needed.

The well known ‘phase system’ used in evaluation of new drugs consists of phases 1, 2 and 3 which are performed before marketing and phase 4 which is carried out after marketing. The pre-marketing phases (1, 2 and 3) aim at describing intended and unintended drug effects in well defined, but rather small, groups of subjects or patients. In contrast, the phase–4 study aims at describing the events following the use of the drug in a larger, more heterogeneous and less well defined population. This system is generally accepted and used in all countries having a modern drug regulatory system, and has generally served its purpose well.