Solai L K, Mulsant B H, Pollock B G, Sweet R A, Rosen J, Yu K, Reynolds C F
Mental Health Clinical Research Center for the Study of Late-Life Mood Disorders, University of Pittsburgh School of Medicine, Pa., USA.
J Clin Psychiatry. 1997 Oct;58(10):440-3. doi: 10.4088/jcp.v58n1006.
Several serotonin selective reuptake inhibitors have been reported to be inhibitors of the cytochrome P450 2D6 (CYP2D6). Thus, they may increase the plasma level of secondary amine tricyclic antidepressants, which are predominantly metabolized through this enzyme. Except for a few case reports, no clinical data document the degree of this drug-drug interaction in elderly depressed patients.
We systematically examined this interaction by determining the change in plasma nortriptyline levels in 14 elderly depressed patients in whom sertraline was added to nortriptyline.
After addition of 50 mg/day of sertraline, the median increase in plasma nortriptyline level over baseline was 2% (range, -26% to 117%; p = .30). In 2 patients (14%), there was an increase of 50% or more. For patients taking higher sertraline doses (N = 7; 100 or 150 mg/day), the median increase in plasma nortriptyline level over baseline was 40% (range, -12% to 239%; p = .08).
Overall, a modest effect of sertraline was observed on nortriptyline metabolism in these elderly depressed patients. This is consistent with prior reports of a weak inhibition of CYP2D6 by sertraline in vitro and in young healthy volunteers. However, some patients showed a change in plasma nortriptyline level that would be considered clinically significant. Thus, careful monitoring of plasma nortriptyline levels is recommended in all patients treated with a combination of nortriptyline and sertraline.
据报道，几种5-羟色胺再摄取抑制剂是细胞色素P450 2D6（CYP2D6）的抑制剂。因此，它们可能会提高主要通过该酶代谢的仲胺三环类抗抑郁药的血浆水平。除了少数病例报告外，尚无临床数据记录老年抑郁症患者中这种药物相互作用的程度。
我们通过测定14例在去甲替林基础上加用舍曲林的老年抑郁症患者的血浆去甲替林水平变化，系统地研究了这种相互作用。
加用50mg/天的舍曲林后，血浆去甲替林水平较基线的中位数升高为2%（范围为-26%至117%；p = 0.30）。2例患者（14%）升高了50%或更多。对于服用较高剂量舍曲林（n = 7；100或150mg/天）的患者，血浆去甲替林水平较基线的中位数升高为40%（范围为-12%至239%；p = 0.08）。
总体而言，在这些老年抑郁症患者中观察到舍曲林对去甲替林代谢有适度影响。这与先前在体外和年轻健康志愿者中舍曲林对CYP2D6的弱抑制作用的报道一致。然而，一些患者的血浆去甲替林水平变化被认为具有临床意义。因此，建议在所有接受去甲替林和舍曲林联合治疗的患者中仔细监测血浆去甲替林水平。
