Increased trimipramine plasma levels during fluvoxamine comedication.
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.
Seifritz
E
E
Psychiatric University Hospital, Department of Psychiatry, University of Basel, Switzerland.
Holsboer-Trachsler
E
E
Hemmeter
U
U
Eap
C B
CB
Baumann
P
P
D000368:Aged; D015283:Citalopram / Q000009:adverse effects / Q000627:therapeutic use; D003866:Depressive Disorder / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D003915:Dextromethorphan / Q000493:pharmacokinetics; D004347:Drug Interactions; D005260:Female; D016666:Fluvoxamine / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008617:Mephenytoin / Q000493:pharmacokinetics; D010641:Phenotype; D014299:Trimipramine / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use
D015283:Citalopram; D014299:Trimipramine; D003915:Dextromethorphan; D016666:Fluvoxamine; D008617:Mephenytoin