The relationship between metabolic activity of the isoenzymes of cytochrome P450 2D6 and the antidepressant therapy (by SSRIs) is the main aim of this paper. The SSRIs are metabolised mainly by the CYP2D6. The genes for the CYP2D6 enzymes are polymorphic and that caused interindividual differences in metabolic activity which is based on the genotype. SSRIs are potent inhibitors of the CYP2D6 activity and that fact may lead to the changes of the metabolic fenotype which may not correspond to metabolic genotype. The result is a great variability in tolerance and effecacy of SSRI′therapy. There may be connections between metabolic activity, genotype and the tolerance of the SSRI′therapy.

        Key words: selective inhibitors of serotonin reuptake (SSRI), cytochrom P450 2D6, metabolic fenotype, extensive metabolizer, poor metabolizer.