INCREASED TRIMIPRAMINE PLASMA-LEVELS DURING FLUVOXAMINE COMEDICATION

A depressive patient, a non-responder to trimipramine (TRI), was comed icated first with citalopram (CIT) and then with fluvoxamine (FLUV). B oth the TRI-CIT and TRI-FLUV combination treatments led to a worsening of the depressive state and to the appearance of panic attacks. The a ddition of FLUV to TRI resulted in a twofold increase of the plasma le vels of TRI and to a slight increase of its N-demethylated and 2-hydro xylated metabolites. These results suggest that the interaction betwee n FLUV and TRI occurred at the level of cytochrome P-450IID6 and cytoc hrome P-450(meph) in this patient, phenotyped as an extensive metaboli zer of both dextromethorphan and mephenytoin. The adverse effects were possibly due to (a) a pharmacokinetic interaction between CIT and FLU V with TRI and/or (b) alterations in serotonergic and/or dopaminergic neurotransmission.