Paroxetine shifts imipramine metabolism.

The combination of selective serotonin reuptake inhibitors with tricyclic antidepressants has proven useful in treatment-resistant depression but has the potential for adverse drug-drug interactions. In the present study, the metabolism of a single dose of imipramine was studied before and after treatment with paroxetine. Paroxetine induced significant elevations of approximately 50% in half-life, area under the curve, and Cmax of imipramine and decreased clearance twofold. The effects on desipramine pharmacokinetics were even more pronounced. These findings indicate a significant interaction of paroxetine with the CYP2D6 isoenzyme.