Metabolism of the newest antidepressants: comparisons with related predecessors.

The need for better acute and long-term treatment for depressive disorders has led to the development of new agents, including escitalopram, duloxetine (Boehringer Ingelheim Corp/Eli Lilly & Co/Eli Lilly Japan KK/Shionogi & Co Ltd) and gepirone. These drugs undergo extensive biotransformation, with cytochrome P450 (CYP) isoforms playing a major role. Escitalopram is biotransformed by CYP2C19, CYP3A4 and CYP2D6; partly extrapolating from studies of citalopram, polymorphism at CYP2C19 and drug interactions at CYP2D6 may be clinically significant. Duloxetine is metabolized by CYP2D6 and CYP1A2, with moderate potential for interactions at CYP2D6. The metabolism of gepirone involves CYP3A4 and to a lesser extent CYP2D6.