Paroxetine increases serum trimipramine concentration. A report of two cases

Paroxetine is a new antidepressant, a selective serotonin reuptake inhibitor (SSRI), which has marked inhibiting effect on microsomal cytochrome P450 enzymes in human liver. In this case report we describe two patients whose serum trimipramine and desmethyltrimipramine concentrations increased markedly when paroxetine was added to their drug therapy. We suggest that this was due to the inhibitory effect of paroxetine on the CYP 2D6‐mediated metabolism of trimipramine. This interaction may be of clinical importance as both patients had side‐effects, such as sedation and orthostatic hypotension, during the simultaneous administration.