ABCB1、ABCG2和SLC22A1基因多态性对接受拉莫三嗪增效疗法治疗的难治性抑郁症患者拉莫三嗪稳态血浆浓度的影响

IF 0.8 4区医学 Q4 CLINICAL NEUROLOGY Clinical Neuropharmacology Pub Date : 2024-09-01 Epub Date: 2024-08-20 DOI:10.1097/WNF.0000000000000607

Yoko Tomori, Takeshi Suzuki, Kazuo Mihara, Goyo Nagai, Shoko Kagawa, Akifumi Nakamura, Kenji Nemoto, Tsuyoshi Kondo

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引用次数: 0

摘要

研究目的作者证明，对于耐药抑郁症患者来说，拉莫三嗪血浆浓度为 12.7 μmol/L 可能是对拉莫三嗪增强疗法产生良好治疗反应的阈值。拉莫三嗪是P-糖蛋白、乳腺癌抗性蛋白和有机阳离子转运体1的底物，它们分别由ABCB1、ABCG2和SLC22A1编码。有几种多态性会影响其功能。本研究调查了这些多态性与接受拉莫三嗪增效治疗的耐药抑郁症患者体内拉莫三嗪的稳态血浆浓度（Css）之间的关系：本研究共纳入了 129 名治疗耐药的抑郁症患者。治疗耐药的定义是，尽管服用了足够剂量和疗程的精神药物，但对至少 3 种精神药物缺乏治疗反应。他们的诊断如下：重度抑郁障碍（58 人）、双相情感障碍 II（52 人）和双相情感障碍 I（19 人）。进行了为期 8 周的拉莫三嗪增强治疗。39名使用丙戊酸钠的患者的拉莫三嗪最终剂量为75毫克/天，90名未使用丙戊酸钠的患者的拉莫三嗪最终剂量为100毫克/天。治疗第 8 周后，于上午 8:00 进行血液采样。使用 LC/MS/MS 对血浆中的拉莫三嗪水平进行定量。聚合酶链反应分析检测了ABCB1 1236C>T、2677G>T/A、3435C>T、ABCG2 421C>A和SLC22A1 1222G>A的多态性：结果：在服用或未服用丙戊酸钠的患者中，未观察到这些多态性与拉莫三嗪的 Css 有明显关系：本研究表明，在接受拉莫三嗪增强疗法治疗的耐药抑郁症患者中，这些基因多态性在控制拉莫三嗪的Css方面不起作用。

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Effect of Genetic Polymorphisms of ABCB1, ABCG2, and SLC22A1 on the Steady-State Plasma Concentrations of Lamotrigine in Treatment-Resistant Depressed Patients Treated With Lamotrigine Augmentation Therapy.

Objectives: The authors have demonstrated that a plasma lamotrigine concentration of 12.7 μmol/L may be a threshold for a good therapeutic response to lamotrigine augmentation therapy in treatment-resistant depressed patients. Lamotrigine is a substrate of P-glycoprotein, breast cancer resistant protein and organic cation transporter 1, which are encoded by ABCB1 , ABCG2 , and SLC22A1 , respectively. There have been several polymorphisms that affect its function. The present study investigated the relationship between these polymorphisms and the steady-state plasma concentrations (Css) of lamotrigine in treatment-resistant depressed patients receiving lamotrigine as augmentation therapy.

Methods: One hundred twenty-nine treatment-resistant depressed patients were included in this study. Treatment resistance is defined as lack of therapeutic response to at least 3 psychotropics despite adequate doses and duration. Their diagnoses were as follows: major depressive disorder (n = 58), bipolar II disorder (n = 52), and bipolar I disorder (n = 19). Lamotrigine augmentation therapy for 8 weeks was conducted. The final lamotrigine doses were 75 mg/d for 39 patients with valproate and 100 mg/d for 90 without it. Blood was sampled at 8:00 am after the 8th week of treatment. Plasma lamotrigine levels were quantified by using LC/MS/MS. The polymorphisms of ABCB1 1236C>T, 2677G>T/A, 3435C>T, ABCG2 421C>A, and SLC22A1 1222G>A were detected by polymerase chain reaction analyses.

Results: No significant relationships were observed between these polymorphisms and the Css of lamotrigine in the patients with or without valproate.

Conclusions: The present study suggests that these genetic polymorphisms do not play a role in controlling the Css of lamotrigine in treatment-resistant depressed patients treated with lamotrigine augmentation therapy.

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来源期刊

Clinical Neuropharmacology 医学-临床神经学

CiteScore

1.20

自引率

10.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Clinical Neuropharmacology is a peer-reviewed journal devoted to the pharmacology of the nervous system in its broadest sense. Coverage ranges from such basic aspects as mechanisms of action, structure-activity relationships, and drug metabolism and pharmacokinetics, to practical clinical problems such as drug interactions, drug toxicity, and therapy for specific syndromes and symptoms. The journal publishes original articles and brief reports, invited and submitted reviews, and letters to the editor. A regular feature is the Patient Management Series: in-depth case presentations with clinical questions and answers.