Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
J Clin Psychiatry. 2009 Dec;70(12):1688-97. doi: 10.4088/JCP.08r04856blu.
Women taking tamoxifen for the treatment or prevention of recurrence of breast cancer are likely to take antidepressants either for a psychiatric disorder or for hot flashes. Recent evidence suggested that some antidepressants inhibit the metabolism of tamoxifen to its more active metabolites by the cytochrome P450 2D6 (CYP2D6) enzyme, thereby decreasing the anticancer effect. This article reviews the literature on the interactions between newer antidepressants and tamoxifen via CYP2D6 and offers treatment recommendations.
A literature search of clinical and nonclinical studies published prior to September 2008 was conducted on PubMed. We performed 3 different searches combining the terms tamoxifen and SSRIs; tamoxifen and CYP2D6 inhibitors; and antidepressant and breast cancer recurrence. A fourth search with CYP2D6 inhibition and the generic names of individual antidepressants was carried out.
Seven clinical research articles were selected. Nonclinical research articles about antidepressants were included if they mentioned in vitro or in vivo inhibition of CYP2D6.
There is consistent evidence that paroxetine and fluoxetine have a large effect on the metabolism of tamoxifen and should not be used. Indirect evidence indicates that bupropion may also have a large effect on the metabolism of tamoxifen. Venlafaxine has little or no effect on the metabolism of tamoxifen and may be considered the safest choice of antidepressants. Desvenlafaxine is not metabolized by the P450 system and may consequently be another option. Mirtazapine has not been extensively studied, but existing research suggests minimal effect on CYP2D6. The remaining commonly prescribed antidepressants have mild to moderate degrees of CYP2D6 inhibition.
Clinicians treating patients with breast cancer should review the prescription profiles of their patients to evaluate the need for treatment modification. There are safe options for the treatment of depression and clinicians and patients should bear in mind the health risks of untreated depressive states.
接受他莫昔芬治疗或预防乳腺癌复发的女性，可能因精神疾病或热潮红而需要服用抗抑郁药。最近的证据表明，一些抗抑郁药通过细胞色素 P450 2D6（CYP2D6）酶抑制他莫昔芬向其更活跃的代谢物的代谢，从而降低抗癌效果。本文综述了关于通过 CYP2D6 新型抗抑郁药与他莫昔芬相互作用的文献，并提供了治疗建议。
对 2008 年 9 月前发表的临床和非临床研究进行了文献检索，检索工具为 PubMed。我们进行了 3 次不同的搜索，将他莫昔芬和 SSRIs、他莫昔芬和 CYP2D6 抑制剂以及抗抑郁药和乳腺癌复发这三个术语结合起来。还进行了第 4 次搜索，搜索 CYP2D6 抑制和个别抗抑郁药的通用名。
选择了 7 篇临床研究文章。如果非临床研究文章提到 CYP2D6 的体外或体内抑制作用，则纳入其中。
有明确的证据表明，帕罗西汀和氟西汀对他莫昔芬的代谢有很大影响，不应使用。间接证据表明，安非他酮也可能对他莫昔芬的代谢有很大影响。文拉法辛对他莫昔芬的代谢影响很小或没有，可被认为是抗抑郁药的最佳选择。去甲文拉法辛不通过 P450 系统代谢，因此可能是另一种选择。米氮平尚未广泛研究，但现有研究表明其对 CYP2D6 的影响最小。其他常用的抗抑郁药对 CYP2D6 的抑制作用较轻或中度。
治疗乳腺癌患者的临床医生应审查患者的处方情况，评估是否需要修改治疗方案。有安全的选择可用于治疗抑郁症，临床医生和患者应牢记未经治疗的抑郁状态的健康风险。
