Recent research has been oriented towards the study of the clinical relevance of measuring free and total plasma levels of antidepressants and their hydroxylated metabolites, as animal experiments suggest that the latter may be clinically active. In central Europe, about 5-10% of the population has a genetic defect in metabolizing debrisoquine. This is of importance for pharmacopsychiatry, as some antidepressants like desipramine, nortriptyline, amitriptyline, imipramine (and possibly maprotiline) are metabolized by the same enzyme as debrisoquine. This observation helps to understand not only the large interindividual differences in the steady-state levels of these drugs but also drug interferences.