[Therapeutic monitoring of tricyclic antidepressant drugs].

Therapeutic drug monitoring (TDM) is used to optimise therapy by an assessment of the drug's plasma concentration. The indications for TDM according to Preskorn are: 1. well defined relationships between plasma concentration of a drug and its therapeutic efficacy, and between plasma level and adverse events and/or toxicity, 2. narrow therapeutic index of a drug, 3. significant interindividual variability of the dose--plasma concentration relationship, 4. delayed onset of action, 5. difficulty in early diagnosis of toxic events. Tricyclic antidepressants (TCA's) fulfill many criteria for TDM. Interethnic and interindividual differences in pharmacokinetics of TCA's lead to pronounced differences of plasma level. Interindividual variability of plasma concentration of TCA's is connected with age, concomitant diseases, genetically determined polimorphism of cytochrome P-450 enzymes (e.g. CYP2D6) and co-medications (the drug may change pharmacokinetic properties of TCA's). There is no clear relationship between plasma concentration of TCA's and therapeutic efficacy of a drug. Contrary there is clear correlation between plasma level and adverse events (especially cardiotoxic and neurotoxic AE). Therapeutic ranges of plasma concentration for TCA's are well established. In the case of SSRI's or newer antidepressants the clear relationship between plasma level and their therapeutic effect, that is their efficacy and tolerability has not been determined yet. The relationships between plasma concentrations and efficacy and tolerability of TCA's, as well as therapeutic ranges of TCA's and other antidepressants are presented in this paper.