@article{ref1,
title="A randomised, double-blind, placebo-controlled study to evaluate the safety and efficacy of lamotrigine in the maintenance treatment of Chinese adult patients with bipolar I disorder",
journal="International journal of bipolar disorders",
year="2022",
author="Zhang, L. and Zhang, H. and Lv, L.-x. and Tan, Q. and Xu, X. and Hu, J. and Zi, L. and Cooper, J. and Phansalkar, A. and Wang, G.",
volume="10",
number="1",
pages="-",
abstract="BACKGROUND: 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. <br><br>METHODS: 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. <br><br>RESULTS: 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. <br><br>CONCLUSIONS: 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. © 2022, The Author(s).<p /><p>Language: en</p>",
language="en",
issn="2194-7511",
doi="10.1186/s40345-022-00266-4",
url="http://dx.doi.org/10.1186/s40345-022-00266-4"
}