INHIBITION OF HEPATIC P-450 ISOENZYMES BY SEROTONIN SELECTIVE REUPTAKE INHIBITORS - IN-VITRO AND IN-VIVO FINDINGS AND THEIR IMPLICATIONS FOR PATIENT-CARE

The effect on hepatic isoenzymes is emerging as the major clinically i mportant distinguishing characteristic among the selective serotonin r euptake inhibitors (SSRIs). Although this fact has only recently gaine d widespread attention, the knowledge that some SSRIs inhibit hepatic metabolism dates back almost 20 years. This paper will first provide a n overview of hepatic isoenzymes and then present the history and our current understanding of the effects of different SSRIs on different h epatic isoenzymes. Most of the attention in this area has focused on d rug-drug interactions. This paper will also review recent work indicat ing that genetically determined differences in hepatic isoenzyme funct ion can be risk factors in the development of a variety of diseases. T he possible implications of this work relative to the long-term use of SSRIs will be discussed.