Citation

Zhang L, Zhang H, Lv LX, Tan Q, Xu X, Hu J, Zi L, Cooper J, Phansalkar A, Wang G. Int. J. Bipolar Disord. 2022; 10(1).

Copyright

(Copyright © 2022, Holtzbrinck Springer Nature Publishing Group)

DOI

10.1186/s40345-022-00266-4

PMID

unavailable

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.

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.

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.

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).

Language: en

Keywords

adult; Prevention; human; female; male; quality of life; insomnia; concussion; randomized controlled trial; suicide attempt; Lamotrigine; Recurrence; Relapse; epilepsy; major clinical study; controlled study; questionnaire; anticonvulsive agent; brain infarction; citalopram; paroxetine; double blind procedure; headache; quetiapine; lithium carbonate; alprazolam; electroconvulsive therapy; drug safety; placebo; follow up; carbamazepine; drug efficacy; multicenter study; lorazepam; valproic acid; rash; bipolar I disorder; lamotrigine; hypomania; maintenance therapy; clonazepam; electrocardiogram; estazolam; DSM-IV; electrocardiography; Bipolar I disorder; monotherapy; aripiprazole; body mass; urinary tract infection; Article; adjuvant therapy; Clinical Global Impression scale; upper respiratory tract infection; chloral hydrate; hypersensitivity; Young Mania Rating Scale; oxazepam; Maintenance; Short Form 36; rhinopharyngitis; QTc interval; Hamilton Depression Rating Scale; Columbia suicide severity rating scale; Mood episode