Abstract: Depression is a complex heterogeneous psychiatric disorder with a potential to cause patient disability worldwide. In the past decades, a number of the first-line drugs (tricyclics, monoamine oxidase inhibitors, serotonin selective reuptake inhibitors, noradrenaline reuptake inhibitors, serotonin and noradrenaline reuptake inhibitors, etc.) had been discovered for the treatment of depression. CYP450 superfamily is involved in the biotransformation of antidepressants mainly through the CYP2D6, CYP2C19, CYP3A4 isoenzymes. Their genetic polymorphisms are closely related to clinical use and the interactions have been already identified between enzymes and antidepressants. This review focuses on drug metabolism and the interaction for CYP450 enzymes. The content may contribute to the development of antidepressant, improvement of the safety of antidepressants and the efficacy of treatment.