Serotonin selective reuptake inhibitor drug interactions and the cytochrome P450 system

The article focuses on the effects of the serotonin selective reuptake inhibitors (SSRIs) on specific drug metabolizing isoenzymes: CYP2D6, CYP3A3/4, CYPIA2, CYP2C9, and CYP2C19. Both in vitro and in vivo data regarding the inhibition potential of the SSRIs at each of these isoenzyme systems are reviewed. In general, the magnitude of the in vivo interactions between the SSRIs and substrates for these isoenzyme systems mirrors to a large extent their in vitro inhibitory potencies. However, in vitro work is limited owing to pharmacokinetic considerations, the effect of metabolites on the isoenzymes, and the likelihood that several isoenzymes are co-responsible for the metabolism of a substrate.