Preskorn Sheldon H, Shah Rozina, Neff Melissa, Golbeck Amanda L, Choi Joe
University of Kansas School of Medicine, Wichita, KS, USA.
J Psychiatr Pract. 2007 Jan;13(1):5-12. doi: 10.1097/00131746-200701000-00002.
Patients taking antidepressants are more likely to also be taking multiple medications, increasing the risk of adverse drug-drug interactions (DDIs). Because of substantial inhibition of one or more cytochrome P450 (CYP) enzymes at therapeutic doses, the selective serotonin reuptake inhibitors fluoxetine, fluvoxamine, and paroxetine have a higher risk of CYP-mediated DDIs than citalopram, escitalopram, and sertraline, which do not substantially inhibit any CYP enzyme.
Prescribing patterns in 2,779 Veterans Affairs (VA) patients who had a prescription for an antidepressant in the preceding year and a current prescription for at least one systemically active drug were analyzed to determine 1) prevalence of drug combinations with potential to cause CYP-mediated DDIs, 2) frequency of combinations of fluoxetine, paroxetine, or sertraline with drugs whose metabolism is principally dependent on CYP 2D6, and 3) use of reduced doses of CYP 2D6 substrate/drugs with narrow therapeutic indices in patients on fluoxetine or paroxetine compared with sertraline.
In 2,779 patients, 55 pairs of drugs with the potential to cause CYP-mediated DDIs occurred in 300 patients (11%), but only 26 of the patients and 6 of the drug pairs were identified by the VA Drug Alert System. Of the 461 patients receiving fluoxetine and/or paroxetine, 39 (8%) were also receiving a CYP 2D6-model substrate/drug with a narrow therapeutic index, 14 (36%) of whom were receiving high enough doses to be at moderate to high risk of a serious DDI.
VA patients on fluoxetine, paroxetine, and sertraline were equally likely to be on drugs whose metabolism is dependent on CYP 2D6, including drugs with narrow therapeutic indices. No differences were found in doses of tricyclic antidepressants (i.e., "victim" drugs), which have narrow therapeutic indices and serious dose-dependent toxicity, when co-prescribed with fluoxetine or paroxetine versus sertraline (i.e., "perpetrator" drugs), despite predictable differences in CYP 2D6-mediated clearance of these drugs.
服用抗抑郁药的患者更有可能同时服用多种药物，这增加了药物不良相互作用（DDIs）的风险。由于在治疗剂量下对一种或多种细胞色素P450（CYP）酶有显著抑制作用，选择性5-羟色胺再摄取抑制剂氟西汀、氟伏沙明和帕罗西汀比西酞普兰、艾司西酞普兰和舍曲林有更高的CYP介导的DDIs风险，后三者不会显著抑制任何CYP酶。
对2779名退伍军人事务部（VA）患者的处方模式进行分析，这些患者上一年有抗抑郁药处方且目前至少有一种全身活性药物的处方，以确定1）可能导致CYP介导的DDIs的药物组合的患病率，2）氟西汀、帕罗西汀或舍曲林与代谢主要依赖CYP 2D6的药物的组合频率，以及3）与舍曲林相比，服用氟西汀或帕罗西汀的患者中使用低剂量CYP 2D6底物/治疗指数窄的药物的情况。
在2779名患者中，300名患者（11%）出现了55对可能导致CYP介导的DDIs的药物组合，但VA药物警报系统仅识别出26名患者和6对药物组合。在461名接受氟西汀和/或帕罗西汀治疗的患者中，39名（8%）也在接受治疗指数窄的CYP 2D6模型底物/药物，其中14名（36%）接受的剂量足够高，有中度至高度严重DDIs风险。
服用氟西汀、帕罗西汀和舍曲林的VA患者同样有可能服用代谢依赖CYP 2D6的药物，包括治疗指数窄的药物。当三环类抗抑郁药（即“受害者”药物）与氟西汀或帕罗西汀（即“肇事者”药物）联合处方时，与与舍曲林联合处方相比，在剂量上未发现差异，尽管这些药物在CYP 2D6介导的清除方面存在可预测的差异，而三环类抗抑郁药治疗指数窄且有严重的剂量依赖性毒性。
