第 2 周时较高的拉莫三嗪血浆浓度是拉莫三嗪相关皮疹的危险因素。

A High Plasma Lamotrigine Concentration at Week 2 as a Risk Factor for Lamotrigine-Related Rash.

机构信息

Departments of Hospital Pharmacy; and.

Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.

出版信息

Ther Drug Monit. 2020 Aug;42(4):631-635. doi: 10.1097/FTD.0000000000000733.

DOI:10.1097/FTD.0000000000000733

PMID:31985552

Abstract

BACKGROUND

Reportedly, a high plasma concentration of lamotrigine plays a role in the development of lamotrigine-related rash. The relationship between plasma concentrations of lamotrigine at week 2 and the lamotrigine-related rash was prospectively studied in 84 patients (22 males and 62 females) with treatment-resistant depressive disorder during an 8-week treatment of lamotrigine augmentation.

METHODS

Eighty-four depressed patients with an insufficient response to at least 3 psychotropics, including antidepressants, mood stabilizers, and atypical antipsychotics, were included. The diagnoses were major depressive disorder (n = 39), bipolar I disorder (n = 10), and bipolar II disorder (n = 35). The final doses of lamotrigine were 100 mg/d for 57 subjects who were not taking valproate and 75 mg/d for 27 subjects taking valproate. Blood sampling was performed at week 2. Lamotrigine plasma concentrations were measured using high-performance liquid chromatography. The development of lamotrigine-related rash was assessed during the 8-week treatment.

RESULTS

Six females developed lamotrigine-related rash. The mean plasma lamotrigine concentrations at week 2 were significantly (P = 0.009) higher in the rash group (4.81 ± 1.23 μmol/L) than in the nonrash group (3.35 ± 1.39 μmol/L). Receiver-operating characteristic analysis indicated that a plasma lamotrigine concentration of 4.38 μmol/L or greater at week 2 was significantly (P < 0.0001) predictive of lamotrigine-related rash. The proportion of patients with a lamotrigine concentration of 4.38 μmol/L or greater was significantly divided by the cutoff point into the rash group and the nonrash group (5/1 versus 13/65, P = 0.001).

CONCLUSIONS

This study suggests that a high plasma lamotrigine concentration during week 2 is a risk factor for lamotrigine-related rash and a plasma lamotrigine concentration of 4.38 μmol/L may be a considered a threshold for rash in treatment-resistant depressive disorder.

摘要

背景

据报道，拉莫三嗪的血浆浓度较高与拉莫三嗪相关皮疹的发生有关。本研究前瞻性地研究了 84 例（22 名男性和 62 名女性）接受拉莫三嗪增效治疗 8 周的治疗抵抗性抑郁障碍患者，在第 2 周时拉莫三嗪的血浆浓度与拉莫三嗪相关皮疹之间的关系。

方法

纳入 84 例至少接受 3 种精神药物（包括抗抑郁药、心境稳定剂和非典型抗精神病药）治疗但反应不佳的抑郁患者。诊断为：单相重性抑郁障碍（n = 39）、双相 I 型障碍（n = 10）和双相 II 型障碍（n = 35）。未服用丙戊酸钠的 57 例患者最终拉莫三嗪剂量为 100 mg/d，服用丙戊酸钠的 27 例患者最终拉莫三嗪剂量为 75 mg/d。在第 2 周进行血样采集。采用高效液相色谱法测定拉莫三嗪的血药浓度。在 8 周的治疗过程中评估拉莫三嗪相关皮疹的发生情况。

结果

6 例女性出现拉莫三嗪相关皮疹。皮疹组（4.81 ± 1.23 μmol/L）第 2 周的平均拉莫三嗪血浆浓度显著高于非皮疹组（3.35 ± 1.39 μmol/L）（P = 0.009）。受试者工作特征分析表明，第 2 周时拉莫三嗪的血浆浓度为 4.38 μmol/L 或更高与拉莫三嗪相关皮疹显著相关（P < 0.0001）。根据截断值，将患者分为拉莫三嗪浓度 4.38 μmol/L 或更高的患者和拉莫三嗪浓度 4.38 μmol/L 以下的患者，皮疹组和非皮疹组的比例差异有统计学意义（5/1 与 13/65，P = 0.001）。