Baumann P
University Department of Adult Psychiatry, Prilly-Lausanne, Switzerland.
Int Clin Psychopharmacol. 1998 Sep;13 Suppl 5:S35-43. doi: 10.1097/00004850-199809005-00008.
Citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline are the selective serotonin reuptake inhibiting antidepressants available. They differ by their chemical structure, metabolism and pharmacokinetics. Cytochrome P-450 of the liver plays an important role in their metabolism, but CYP1A2, CYP2C19, CYP2D6, CYP3A4 and possibly some other isoforms differ by their relative contribution. Citalopram and fluoxetine are available as racemic compounds: stereospecificity of their enantiomers has been shown for their serotonergic pharmacology, metabolism and kinetics. The pharmacokinetics of drugs may be modified in elderly patients, at different levels: absorption, distribution, metabolism and excretion. In these patients, depending on the selective serotonin reuptake inhibitor (SSRI) used, it is recommended to adapt the dose of the antidepressant: Lower doses should be used for citalopram, paroxetine and probably also for sertraline, when therapy is initiated. No clear evidence was found for fluoxetine and fluvoxamine concerning an age dependent metabolism. As elderly depressive patients may also suffer from somatic diseases, this should be considered in the choice of the dose of an SSRI, as for some of them, elimination is decreased in hepatic (citalopram, fluoxetine, fluvoxamine, sertraline) or renal (paroxetine) impairments.
西酞普兰、氟西汀、氟伏沙明、帕罗西汀和舍曲林是现有的选择性5-羟色胺再摄取抑制型抗抑郁药。它们在化学结构、代谢和药代动力学方面存在差异。肝脏中的细胞色素P-450在它们的代谢中起重要作用,但CYP1A2、CYP2C19、CYP2D6、CYP3A4以及可能的其他一些同工酶在相对贡献方面有所不同。西酞普兰和氟西汀以消旋化合物形式存在:已表明它们对映体的立体特异性体现在其血清素能药理学、代谢和动力学方面。药物的药代动力学在老年患者中可能会在不同层面发生改变:吸收、分布、代谢和排泄。在这些患者中,根据所使用的选择性5-羟色胺再摄取抑制剂(SSRI),建议调整抗抑郁药的剂量:开始治疗时,西酞普兰、帕罗西汀以及可能还有舍曲林应使用较低剂量。关于氟西汀和氟伏沙明,未发现有明确证据表明存在年龄依赖性代谢。由于老年抑郁症患者可能还患有躯体疾病,在选择SSRI的剂量时应考虑到这一点,因为对于其中一些患者,在肝脏(西酞普兰、氟西汀、氟伏沙明、舍曲林)或肾脏(帕罗西汀)功能受损时,药物消除会减少。