Clinical Summary
Clinical Summary: Preventive Effects of Lamotrigine in Bipolar II Versus Bipolar I Disorder
Patients with bipolar II disorder often cycle through recurrent depressive and hypomanic episodes, yet most maintenance data for mood stabilizers come from bipolar I disorder. This study addresses a practical prescribing question: whether lamotrigine prevents recurrence/relapse more effectively in bipolar II disorder than in bipolar I disorder in routine clinical care.
Design
an open-label, noninterventional, naturalistic, prospective postmarketing surveillance study of lamotrigine
N
Of these, 191 BPI and 399 BPII patients were included as analysis sets because data were available for all patient characteristics investigated.
Population
Japanese inpatients as well as outpatients diagnosed with bipolar disorder according to DSM-IV-TR, who were prescribed lamotrigine for the first time in daily clinical practice to prevent recurrence/relapse of mood episodes
Duration
The observation period for each patient was 1 year.
Key Findings
- Lamotrigine was associated with a significantly longer time to recurrence/relapse of mood episodes in BPII than in BPI (log-rank test, P = .0103).
- The between-diagnosis difference was driven by mania-related outcomes: lamotrigine significantly prolonged time to recurrence/relapse of mania-related episodes in BPII patients compared with BPI patients (P = .0110), while there was no difference in time to major depressive episodes (P = .2468).
- The estimated times to recurrence/relapse of mood episodes by bipolar diagnosis (25th percentile) were 71 days and 183 days for BPI and BPII, respectively.
- In Cox proportional hazards regression, only diagnosis was selected as an influential factor, with hazard ratio in BPI = 1.4506 for BPII; 95% CI, 1.0893-1.9316; P = .0109.
- Adverse drug reactions were similar by diagnosis at 22.0% (n = 42/191) in BPI and 21.8% (n = 87/399) in BPII; skin disorders occurred in 11.5% (n = 22/191) and 11.5% (n = 46/399), respectively.
Clinical Bottom Line
Lamotrigine maintenance was associated with longer time to recurrence/relapse in bipolar II disorder than in bipolar I disorder over 1 year, without a higher adverse drug reaction burden. In practice, lamotrigine is a strong maintenance option for bipolar II disorder, with the apparent advantage arising from mania-related rather than depressive outcomes.
Practice Implications
- Consider lamotrigine as a maintenance treatment option in bipolar II disorder when recurrence prevention is the goal, as the 25th percentile time to recurrence/relapse was 183 days in BPII versus 71 days in BPI.
- When counseling patients, set expectations that the between-group advantage in this study was seen for mania-related episodes (P = .0110), not for major depressive episodes (P = .2468).
- Do not assume the observed BPII advantage was explained by more intensive co-treatment: despite higher concomitant lithium (47.6% vs 26.3%), valproate sodium (25.1% vs 16.5%), and atypical antipsychotic use (51.3% vs 31.6%) in BPI, diagnosis remained the only selected predictor in Cox analysis.
- Monitor closely for rash and follow the package-insert titration schedule, since skin disorders occurred in 11.5% of both groups and serious skin disorders occurred in 0.5% (n = 1/191) in BPI and 1.5% (n = 6/399) in BPII.
