Are pharmacokinetic drug interactions with the SSRIs an issue?

The development of the selective serotonin reuptake inhibitors (SSRIs) began 20 years ago, around the time when it was discovered that the cytochrome P450 system consists of multiple drug-metabolizing enzymes. There are 5-10 important drug-metabolizing P450 enzymes in the human liver, and their relationship with SSRIs has been studied intensively during the last 5 years. Thus, among the SSRIs, fluvoxamine is the only very potent inhibitor of cytochrome P4501A2 (CYP1A2). All of the SSRIs inhibit CYP2D6 ('sparteine/debrisoquine oxygenase') but fluoxetine and paroxetine are clearly the most potent in this regard. Fluoxetine and fluvoxamine are moderate inhibitors of CYP2C19 ('S-mephenytoinhydroxylase'), and fluvoxamine might also be a moderate inhibitor of CYP2C9. Thus, although much still has to be learned about SSRIs and cytochrome P450, it seems that citalopram and sertraline have the most favourable profile in relation to drug interactions.