, Volume 110, Issue 3, pp 302–308 | Cite as

Inhibition of antidepressant demethylation and hydroxylation by fluvoxamine in depressed patients

  • Sebastian Härtter
  • Hermann Wetzel
  • Elke Hammes
  • Christoph Hiemke
Original Investigations


Bidirectional drug interactions between fluvoxamine and classical antidepressants were studied in depressed patients. A column switching technique combined with high performance liquid chromatography (HPLC) enabled automated analyses of plasma for simultaneous determination of fluvoxamine, tricyclic and tetracyclic antidepressants and demethylated and major hydroxylated metabolites in a single HPLC run. The measurements revealed that fluvoxamine inhibited N-demethylation of imipramine, clomipramine, amitriptyline and maprotiline whereas interferences with hydroxylation reactions were restricted to aromatic 8-hydroxylation of clomipramine. In patients under fluvoxamine monotherapy before comedication, plasma concentrations of fluvoxamine increased after administration of a tricyclic antidepressant, thus indicating bidirectional drug interactions. The inhibitory effects of fluvoxamine on the metabolism of classical antidepressants disappeared after discontinuation of concomitant fluvoxamine treatment within at least 1–2 weeks. The reported alterations in drug metabolism observed in depressed patients who were under fluvoxamine/tricyclic antidepressant comedication suggested that careful supervision and regular drug monitoring are necessary in such patients.

Key words

Fluvoxamine Tricylic antidepressants Plasma concentrations Drug interactions Clomipramine N-Demethylation Hydroxylation 


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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Sebastian Härtter
    • 1
  • Hermann Wetzel
    • 1
  • Elke Hammes
    • 1
  • Christoph Hiemke
    • 1
  1. 1.Department of PsychiatryUniversity of MainzMainzFederal Republic of Germany

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