Increased trimipramine plasma levels during fluvoxamine comedication

Eur Neuropsychopharmacol. 1994 Mar;4(1):15-20. doi: 10.1016/0924-977x(94)90310-7.


A depressive patient, a non-responder to trimipramine (TRI), was comedicated first with citalopram (CIT) and then with fluvoxamine (FLUV). Both the TRI-CIT and TRI-FLUV combination treatments led to a worsening of the depressive state and to the appearance of panic attacks. The addition of FLUV to TRI resulted in a twofold increase of the plasma levels of TRI and to a slight increase of its N-demethylated and 2-hydroxylated metabolites. These results suggest that the interaction between FLUV and TRI occurred at the level of cytochrome P-450IID6 and cytochrome P-450meph in this patient, phenotyped as an extensive metabolizer of both dextromethorphan and mephenytoin. The adverse effects were possibly due to (a) a pharmacokinetic interaction between CIT and FLUV with TRI and/or (b) alterations in serotonergic and/or dopaminergic neurotransmission.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Citalopram / adverse effects
  • Citalopram / therapeutic use
  • Depressive Disorder / blood*
  • Depressive Disorder / complications
  • Depressive Disorder / drug therapy
  • Dextromethorphan / pharmacokinetics
  • Drug Interactions
  • Female
  • Fluvoxamine / adverse effects*
  • Fluvoxamine / therapeutic use
  • Humans
  • Mephenytoin / pharmacokinetics
  • Phenotype
  • Trimipramine / adverse effects
  • Trimipramine / blood*
  • Trimipramine / therapeutic use


  • Citalopram
  • Trimipramine
  • Dextromethorphan
  • Fluvoxamine
  • Mephenytoin