Richelson E
Department of Psychiatry and Psychology, Mayo Clinic Jacksonville, FL 32224, USA.
Mayo Clin Proc. 1997 Sep;72(9):835-47. doi: 10.4065/72.9.835.
Seven of the newest antidepressants are the serotonin-selective reuptake inhibitors (fluoxetine, sertraline, paroxetine, and fluvoxamine [currently approved in the United States only for obsessive-compulsive disorder]), a serotonin-norepinephrine reuptake inhibitor (venlafaxine), a postsynaptic serotonin antagonist-presynaptic serotonin reuptake inhibitor (nefazodone), and a presynaptic-postsynaptic noradrenergic-serotonergic receptor antagonist (mirtazapine). Many of these drugs are potent inhibitors of the cytochrome P-450 enzymes (CYPs) of the liver. The isoforms of the CYPs most relevant to the use of antidepressants are CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. CYP inhibition may affect the metabolism of numerous drugs in several classes that are substrates for these isoenzymes, with potentially serious consequences. To minimize the potential for an adverse event, the practitioner must remember the drug-drug interactions, and possible consequences when one of these antidepressants is being prescribed. A "primer" on drug metabolism is included herein, which serves as a basis for understanding these interactions., Each of the isoenzymes of the CYPs is discussed in relationship to the drugs they metabolize, and appropriate cautions are recommended for concurrent administration of these new antidepressants and other drugs most frequently prescribed to elderly patients.
七种最新的抗抑郁药包括5-羟色胺选择性再摄取抑制剂（氟西汀、舍曲林、帕罗西汀和氟伏沙明[目前在美国仅被批准用于强迫症]）、一种5-羟色胺-去甲肾上腺素再摄取抑制剂（文拉法辛）、一种突触后5-羟色胺拮抗剂-突触前5-羟色胺再摄取抑制剂（奈法唑酮）以及一种突触前-突触后去甲肾上腺素能-5-羟色胺能受体拮抗剂（米氮平）。这些药物中的许多都是肝脏细胞色素P-450酶（CYPs）的强效抑制剂。与抗抑郁药使用最相关的CYPs同工酶是CYP1A2、CYP2C9、CYP2C19、CYP2D6和CYP3A4。CYP抑制可能会影响众多作为这些同工酶底物的几类药物的代谢，可能产生严重后果。为了将不良事件的可能性降至最低，从业者必须记住药物相互作用以及开具这些抗抑郁药之一时可能产生的后果。本文包含了一份药物代谢“入门知识”，作为理解这些相互作用的基础。将针对CYPs的每种同工酶与其代谢的药物进行讨论，并针对这些新型抗抑郁药与老年患者最常开具的其他药物联合使用时给出适当的注意事项。
