5-羟色胺再摄取抑制剂抗抑郁药,包括选择性5-羟色胺再摄取抑制剂(SSRIs;即西酞普兰,艾司西酞普兰,氟西汀,氟伏沙明,帕罗西汀,和舍曲林),5-羟色胺和去甲肾上腺素再摄取抑制剂(SNRIs;即去文拉法辛,度洛西汀,levomilnacipran,米纳西普兰,和文拉法辛),和具有SSRI样特性的血清素调节剂(即,维拉唑酮和沃替西汀)是重度抑郁症和焦虑症的主要药物治疗方法。CYP2D6,CYP2C19和CYP2B6的遗传变异会影响许多抗抑郁药的代谢,这可能会影响剂量,功效,和耐受性。此外,已经检查了药效学基因SLC6A4(5-羟色胺转运蛋白)和HTR2A(5-羟色胺-2A受体)与这些药物的疗效和副作用的关系。本指南更新并扩展了2015年CYP2D6和CYP2C19基因型和SSRI给药的临床药物遗传学实施联盟(CPIC)指南,并总结了CYP2D6,CYP2C19,CYP2B6,SLC6A4和HTR2A基因型对抗抑郁药给药的影响。功效,和耐受性。我们提供了使用CYP2D6,CYP2C19和CYP2B6基因型结果的建议,以帮助告知这些抗抑郁药的处方,并描述了SLC6A4和HTR2A的现有数据,这些数据不支持其在抗抑郁药处方中的临床使用。
Serotonin reuptake inhibitor antidepressants, including selective serotonin reuptake inhibitors (SSRIs; i.e., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), serotonin and norepinephrine reuptake inhibitors (i.e., desvenlafaxine, duloxetine, levomilnacipran, milnacipran, and venlafaxine), and serotonin modulators with SSRI-like properties (i.e., vilazodone and vortioxetine) are primary pharmacologic treatments for major depressive and anxiety disorders. Genetic variation in CYP2D6, CYP2C19, and CYP2B6 influences the metabolism of many of these antidepressants, which may potentially affect dosing, efficacy, and tolerability. In addition, the pharmacodynamic genes SLC6A4 (serotonin transporter) and HTR2A (serotonin-2A receptor) have been examined in relation to efficacy and side effect profiles of these drugs. This
guideline updates and expands the 2015 Clinical
Pharmacogenetics Implementation Consortium (CPIC)
guideline for CYP2D6 and CYP2C19 genotypes and SSRI dosing and summarizes the impact of CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A genotypes on antidepressant dosing, efficacy, and tolerability. We provide recommendations for using CYP2D6, CYP2C19, and CYP2B6 genotype results to help inform prescribing these antidepressants and describe the existing data for SLC6A4 and HTR2A, which do not support their clinical use in antidepressant prescribing.