Kagawa Shoko, Mihara Kazuo, Nakamura Akifumi, Nemoto Kenji, Suzuki Takeshi, Nagai Goyo, Kondo Tsuyoshi
Departments of *Neuropsychiatry, and †Pharmacy, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Ther Drug Monit. 2014 Dec;36(6):730-3. doi: 10.1097/FTD.0000000000000088.
The relationship between plasma concentrations of lamotrigine and its therapeutic effects was prospectively studied on 34 (9 men and 25 women) inpatients with treatment-resistant depressive disorder during an 8-week treatment of lamotrigine augmentation using an open-study design.
The subjects were depressed patients who had already shown insufficient response to at least 3 psychotropics, including antidepressants, mood stabilizers, and atypical antipsychotics. The diagnoses were major depressive disorder (n = 12), bipolar I disorder (n = 7), and bipolar II disorder (n = 15). The final doses of lamotrigine were 100 mg/d for 18 subjects who were not taking valproate and 75 mg/d for 16 subjects taking valproate. Depressive symptoms were evaluated by the Montgomery Åsberg Depression Rating Scale (MADRS) before and after the 8-week treatment. Blood sampling was performed at week 8. Plasma concentrations of lamotrigine were measured by high-performance liquid chromatography.
There was a significant linear relationship between the plasma concentrations of lamotrigine and percentage improvements at week 8 (r = 0.418, P < 0.05). A stepwise multiple regression analysis showed that plasma lamotrigine concentrations alone had a significant effect on the percentage improvements at week 8 (standardized partial correlation coefficients = 0.454, P < 0.001). The receiver operating characteristics analysis indicated that a plasma lamotrigine concentration of 12.7 μmol/L or greater was significantly (P < 0.001) predictive of response (50% or more reduction in the MADRS score). The proportion of the responders was significantly higher in the groups with a lamotrigine concentration >12.7 μmol/L (11/15 versus 4/19, P < 0.01).
The present study suggests that an early therapeutic response to lamotrigine is dependent on its plasma concentration and that a plasma lamotrigine concentration of 12.7 μmol/L may be a threshold for a good therapeutic response in treatment-resistant depressive disorder.
采用开放研究设计，对34例（9例男性和25例女性）难治性抑郁症住院患者在为期8周的拉莫三嗪增效治疗期间，前瞻性研究了拉莫三嗪血浆浓度与其治疗效果之间的关系。
受试者为对至少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）反应不足的抑郁症患者。诊断为重度抑郁症（n = 12）、双相I型障碍（n = 7）和双相II型障碍（n = 15）。未服用丙戊酸盐的18名受试者拉莫三嗪的最终剂量为100mg/d，服用丙戊酸盐的16名受试者为75mg/d。在8周治疗前后，通过蒙哥马利-Åsberg抑郁评定量表（MADRS）评估抑郁症状。在第8周进行血液采样。通过高效液相色谱法测量拉莫三嗪的血浆浓度。
拉莫三嗪血浆浓度与第8周的改善百分比之间存在显著的线性关系（r = 0.418，P < 0.05）。逐步多元回归分析表明，仅拉莫三嗪血浆浓度对第8周的改善百分比有显著影响（标准化偏相关系数 = 0.454，P < 0.001）。受试者工作特征分析表明，血浆拉莫三嗪浓度为12.7μmol/L或更高时，对反应有显著预测性（P < 0.001）（MADRS评分降低50%或更多）。拉莫三嗪浓度>12.7μmol/L的组中反应者的比例显著更高（11/15对4/19，P < 0.01）。
本研究表明，拉莫三嗪的早期治疗反应取决于其血浆浓度，血浆拉莫三嗪浓度为12.7μmol/L可能是难治性抑郁症良好治疗反应的阈值。
