INTERACTION BETWEEN AMITRIPTYLINE AND PHENOTHIAZINE IN MAN - EFFECT ON PLASMA-CONCENTRATION OF AMITRIPTYLINE AND ITS METABOLITE NORTRIPTYLINE AND THE CORRELATION WITH CLINICAL-RESPONSE

Amitriptyline (AT) and nortriptyline (NT) plasma levels were checked in 86 patients treated with AT by oral or IM administration. Fifty-six patients were also treated with a phenothiazine. In 20 of these patients receiving AT IM with a phenothiazine, the plasma levels of NT (and the variability of these levels between patients) were higher than in nine patients receiving the antidepressant drug alone at the same dosage and by the same route. In eleven patients receiving AT orally with a phenothiazine the plasma levels of NT (and the variability of these levels between patients) were higher, and the ratio of plasma levels of AT and NT were lower than in eight patients receiving the antidepressant drug alone at the same dosage and by the same route. These results suggest an increase of the demethylation of AT and/or a decrease of the hydroxylation of NT and/or a decrease of its elimination. The differences in the variability of the plasma levels of AT and NT could be due to a saturation of the enzymatic system of biotransformation of the antidepressant drug by phenothiazine and to a first-pass effect when the drug is given orally. The correlation between the plasma levels of AT and NT and the clinical effect has been studied in the 86 patients. The correlation between the NT plasma level and the clinical response seems to be more curvilinear when AT is associated with a phenothiazine. This suggests a potentialization of the post-synaptic alpha-receptor blocking effect of NT by the neuroleptic drug. © 1979 Springer-Verlag.