Effectiveness of Lamotrigine Adjunctive Treatment of Depressive Symptoms in Patients with Bipolar Disorder Not Otherwise Specified: A 52-Week Prospective Naturalistic Study

Moon, Eunsoo; Chang, Jae Seung; Cha, Boseok; Yun, Je Yeon; Ha, Tae Hyon; Ha, Kyooseob

Abstract

OBJECTIVE
The pharmacotherapy of bipolar disorder not otherwise specified (BP-NOS) has been insufficiently studied. The aim of this prospective naturalistic study was to explore the effectiveness of lamotrigine adjunctive treatment in patients with BP-NOS.
METHODS
Data from 50 patients diagnosed with BP-NOS were analyzed. On the basis of the prospective mood chart methodology, the efficacy of lamotrigine adjunctive treatment was assessed by changes in the mean Clinical Global Impressions-Bipolar Version (CGI-BP) depression scores. A paired t-test was used to test the statistical significance of the changes in CGI-BP depression scores. Repeated-measures analysis of variance (RM ANOVA) with simple effect analysis was performed to explore the sequential changes during a 52-week period. Cohen's d was calculated to measure the magnitude of the treatment effects on the changes in depression severity. Time to lamotrigine discontinuation was also calculated using the Kaplan-Meier estimates. Lamotrigine-associated adverse events were monitored every two weeks.
RESULTS
A significant decrease, with a large effect size (Cohen's d=1.6), in the mean CGI-BP depression scores was associated with lamotrigine adjunctive treatment in intent-to-treat analysis (t=8.7, df=49, p<0.001). Twenty-four patients (48.0%) completed 52-week lamotrigine adjunctive treatment. Analysis of the data obtained from those completing the treatment revealed a large effect (Cohen's d=4.0) on improvement in the severity of depression (t=16.8, df=32, p<0.001). Sixty percent of patients achieved remission (n=30), and 64% of patients (n=32) showed some clinical response to lamotrigine adjunctive treatment. The mean time to lamotrigine discontinuation was 31.3+/-3.1 weeks (CI=25.2-37.4). Lamotrigine adjunctive treatment was well tolerated, with no serious rashes reported.
CONCLUSION
Lamotrigine seems to be effective in the management of depressive symptoms in BP-NOS. Long-term use of lamotrigine was generally safe and well tolerated. Large-scale controlled trials might be needed to confirm the findings of this naturalistic study.