Relationship Between UGT1A4 and UGT2B7 Polymorphisms and the Steady-State Plasma Concentrations of Lamotrigine in Patients With Treatment-Resistant Depressive Disorder Receiving Lamotrigine as Augmentation Therapy
Relationship Between UGT1A4 and UGT2B7 Polymorphisms and the Steady-State Plasma Concentrations of Lamotrigine in Patients With Treatment-Resistant Depressive Disorder Receiving Lamotrigine as Augmentation Therapy
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DOI：
10.1097/ftd.0000000000000577
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发表时间：
2019-02-01
影响因子：
2.5
通讯作者：
Kondo, Tsuyoshi
中科院分区：
文献类型：
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作者：
Suzuki, Takeshi;Mihara, Kazuo;Kondo, Tsuyoshi
背景资料：在以前的研究中，作者已经表明，在难治性抑郁症中，拉莫三嗪强化治疗的早期治疗反应取决于其血浆浓度。拉莫三嗪主要由UGT 1A 4和UGT 2B 7代谢，并且已经报道了影响酶活性的所述UGT的多态性。本研究探讨了这些多态性对拉莫三嗪的稳态血药浓度（Css）的影响，在治疗难治性抑郁症患者接受拉莫三嗪作为增强therapy.Methods：受试者是103例抑郁症患者已经表现出不足的反应，至少有3个精神药物，包括抗抑郁药，情绪稳定剂，非典型抗精神病药。诊断为重度抑郁症（n = 46）、双相II型障碍（n = 44）和双相I型障碍（n = 13）。接受拉莫三嗪强化治疗8周。拉莫三嗪的最终剂量分别为100 mg/d（67例未使用丙戊酸盐的受试者）和75 mg/d（36例使用丙戊酸盐的受试者）。在第8周进行血液采样。拉莫三嗪的血药浓度采用高效液相色谱法测定。聚合酶链反应分析UGT 1A 4 142 T>G、UGT 2B 7-161 C>T和UGT 2B 7 372>G基因型。结果：无论是否合并使用丙戊酸盐，这些多态性与拉莫三嗪的Css无显著相关性。这项研究表明，这些遗传多态性不影响拉莫三嗪治疗患者的Css-接受拉莫三嗪强化治疗的难治性抑郁症。
Background: In a previous study, the authors had shown that in treatment-resistant depressive disorder, an early therapeutic response to lamotrigine augmentation therapy is dependent on its plasma concentrations. Lamotrigine is mainly metabolized by UGT1A4 and UGT2B7, and polymorphisms of said UGTs that affect enzyme activities have been reported. This study investigated the effect of these polymorphisms on the steady-state plasma concentrations (Css) of lamotrigine in patients with treatment-resistant depressive disorder receiving lamotrigine as augmentation therapy.Methods: The subjects were 103 depressed patients who had already shown insufficient response to at least 3 psychotropics including antidepressants, mood stabilizers, and atypical antipsy-chotics. The diagnoses were major depressive disorder (n - 46), bipolar II disorder (n = 44), and bipolar I disorder (n = 13). They received augmentation therapy with lamotrigine for 8 weeks. The final doses of lamotrigine were 100 mg/d for 67 subjects who were not taking valproate and 75 mg/d for 36 subjects taking valproate, respectively. Blood sampling was performed at the 8th week. Plasma concentrations of lamotrigine were measured by high-performance liquid chromatography. The genotypes of UGT1A4 142T>G, UGT2B7 -161C>T, and UGT2B7 372>G were identified by polymerase chain reaction analyses.Results: There were no significant relationships between these polymorphisms and the Css of lamotrigine in the subjects regardless of valproate comedication.Conclusions: This study suggests that these genetic polymorphisms do not affect the Css of lamotrigine in patients with treatment-resistant depressive disorder receiving lamotrigine as augmentation therapy.