Ssri hepatic enzyme inhibitor

Fluoxetine and paroxetine are potent inhibitors of a hepatic CYP450 isoenzyme (CYP2D6) responsible for the elimination of TCAs, neuroleptic drugs, and some antiarrhythmic and β-adrenergic antagonist drugs. [Note: About 7 percent of the Caucasian population lacks this P450 enzyme and, therefore, metabolize fluoxetine and other substrates of this enzyme very slowly. These individuals may be referred to in the literature as “poor metabolizers.”] Other cytochrome enzymes (CYP2C9/19, CYP3A4, CYP1A2) are involved with SSRI metabolism and may also be inhibited to various degrees by the SSRIs. Thus, they may affect the metabolism of multiple medications. Fluoxetine inhibits CYP2D6 and to a lesser extent CYP3A4 isoforms; fluvoxamine inhibits CYP1A2 and paroxetine CYP2D6. Through its inhibition of CYP2D6, fluoxetine can increase plasma levels of several drugs including dextromethorphan, propranolol, tamoxifen, and the TCAs. Citalopram causes fewer drug interactions than other SSRIs.