Zhang Ling, Zhang Honggeng, Lv Lu-Xian, Tan Qingrong, Xu Xiufeng, Hu Jian, Zi Lu, Cooper James, Phansalkar Abhay, Wang Gang
The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital , Capital Medical University, 100088, Beijing, China.
Department of Psychiatry, Brains Hospital of Hunan Province, Changsha, China.
Int J Bipolar Disord. 2022 Aug 1;10(1):20. doi: 10.1186/s40345-022-00266-4.
Lamotrigine is approved as a maintenance therapy for bipolar I disorder in many countries, including China in 2021. This study evaluated the efficacy and safety of lamotrigine in controlling relapse and/or recurrence of mood episodes in Chinese patients with bipolar I disorder.
Patients aged ≥ 18 years with bipolar I disorder who met response criteria (Clinical Global Impression-Severity [CGI-S] score of ≤ 3 for ≥ 4 consecutive weeks) during treatment with lamotrigine in a 6-16 week open-label (OL) phase, and who were maintained for ≥ 1 week on lamotrigine 200 mg/day monotherapy, were randomised (1:1) to continue receiving lamotrigine 200 mg/day or switch to placebo in a 36-week randomised double-blind (RD) phase. The primary efficacy outcome measure was time from entry into the RD phase to intervention for relapse and/or recurrence of a mood episode (TIME). Post hoc analyses assessed the impact of OL baseline mood severity on TIME. Safety assessments were conducted throughout the study.
Of 420 patients treated in the OL phase, 264 were randomised to receive lamotrigine (n = 131) or placebo (n = 133). Overall, 112 patients had an intervention for relapse and/or recurrence of a mood episode (lamotrigine, n = 50/130 [38.5%]; placebo, n = 62/133 [46.6%]), with no significant difference in TIME between groups (adjusted hazard ratio [95% confidence interval (CI)] 0.93 [0.64, 1.35]; p = 0.701). Post hoc analyses indicated a significant difference in TIME, favouring lamotrigine over placebo, for patients with baseline CGI-S score ≥ 4 (hazard ratio [95% CI] 0.52 [0.30, 0.89]; p = 0.018) and with baseline Hamilton Depression Rating Scale ≥ 18 or Young Mania Rating Scale ≥ 10 (0.44 [hazard ratio [95% CI] 0.25, 0.78]; p = 0.005). Lamotrigine was well tolerated with no new safety signals.
Lamotrigine was not significantly superior to placebo in preventing relapse and/or recurrence of mood episodes in this study of Chinese patients with bipolar I disorder but post hoc analyses suggested a therapeutic benefit in patients with moderate/severe mood symptoms at baseline. The discrepancy between these findings and the positive findings of the pivotal studies may be attributable to the symptom severity of the bipolar patients recruited, a high dropout rate, and the comparatively short duration of the RD phase rather than race/ethnicity differences. Clinical trial registration ClinicalTrial.gov Identifier NCT01602510; 21st May 2012; https://clinicaltrials.gov/ct2/show/NCT01602510 .
拉莫三嗪在包括中国（2021年）在内的许多国家被批准作为双相I型障碍的维持治疗药物。本研究评估了拉莫三嗪在中国双相I型障碍患者中控制情绪发作复发和/或再发的疗效和安全性。
年龄≥18岁的双相I型障碍患者，在为期6 - 16周的开放标签（OL）阶段接受拉莫三嗪治疗期间达到反应标准（临床总体印象-严重程度[CGI-S]评分连续≥4周≤3），且以拉莫三嗪200mg/天单药维持治疗≥1周，在为期36周的随机双盲（RD）阶段被随机分组（1:1），继续接受拉莫三嗪200mg/天治疗或换用安慰剂。主要疗效指标是从进入RD阶段到因情绪发作复发和/或再发进行干预的时间（TIME）。事后分析评估了OL基线情绪严重程度对TIME的影响。在整个研究过程中进行安全性评估。
在OL阶段治疗的420例患者中，264例被随机分组接受拉莫三嗪（n = 131）或安慰剂（n = 133）。总体而言，112例患者因情绪发作复发和/或再发接受了干预（拉莫三嗪组，n = 50/130 [38.5%]；安慰剂组，n = 62/133 [46.6%]），两组之间的TIME无显著差异（调整后的风险比[95%置信区间（CI）] 0.93 [0.64, 1.35]；p = 0.701）。事后分析表明，对于基线CGI-S评分≥4的患者（风险比[95% CI] 0.52 [0.30, 0.89]；p = 0.018）以及基线汉密尔顿抑郁量表评分≥18或杨氏躁狂量表评分≥10的患者（风险比[9,5% CI] 0.44 [0.2,5, 0.78]；p = 0.005），TIME存在显著差异，拉莫三嗪优于安慰剂。拉莫三嗪耐受性良好，无新的安全信号。
在本项针对中国双相I型障碍患者的研究中，拉莫三嗪在预防情绪发作复发和/或再发方面并不显著优于安慰剂，但事后分析表明，对于基线有中度/重度情绪症状的患者有治疗益处。这些研究结果与关键研究的阳性结果之间的差异可能归因于所招募双相患者的症状严重程度、高脱落率以及RD阶段相对较短的持续时间，而非种族/民族差异。临床试验注册ClinicalTrial.gov标识符NCT01602510；2012年5月21日；https://clinicaltrials.gov/ct2/show/NCT01602510 。
