[A case of metabolic interaction: amitriptyline, fluoxetine, antitubercular agents]

Polytherapy is often used in clinical practice. The drug associations may lead to pharmacokinetic and/or pharmacodynamic interactions, with clinical implications. The authors reported a quantified illustration of 2 types of interactions in a depressed patient: between antidepressants, amitriptyline and fluoxetine, between these antidepressants and antituberculosis. Firstly, when fluoxetine was added to amitriptyline, it was observed, as expected, an increase of the tricyclic and its metabolite plasma levels, despite a decrease of its dosage. Secondly, when antituberculosis were added to the 2 antidepressants, it was observed a decrease of the tricyclic drug plasma levels. These levels remained below the therapeutic window even when the tricyclic antidepressant dosage was increased. It seems that the fluoxetine interaction disappeared. The competition between the inhibitory effect of fluoxetine and the induction of rifampicin, on the metabolism of amitriptyline is discussed.