Frequently Asked Questions

Yes. Lamotrigine was associated with a significantly longer time to recurrence/relapse of mood episodes in bipolar II disorder than in bipolar I disorder over 1 year of observation (log-rank P = .0103). The estimated 25th percentile time to recurrence/relapse of any mood episode was 183 days in bipolar II disorder versus 71 days in bipolar I disorder.

The between-diagnosis difference was driven by mania-related outcomes, not depressive outcomes. Lamotrigine significantly prolonged time to recurrence/relapse of mania-related episodes, including hypomanic episodes, in bipolar II disorder compared with bipolar I disorder (P = .0110), while there was no significant difference between groups in time to recurrence/relapse of major depressive episodes (P = .2468).

In the Cox proportional hazards regression, diagnosis was the only selected influential factor for time to recurrence/relapse of mood episodes. The reported hazard ratio was 1.4506 with 95% CI, 1.0893-1.9316; P = .0109, indicating that bipolar diagnosis remained associated with recurrence/relapse timing even after candidate baseline variables were examined.

This was an open-label, noninterventional, naturalistic, prospective postmarketing surveillance study in Japanese inpatients and outpatients diagnosed with bipolar I or bipolar II disorder by DSM-IV-TR. Patients were prescribed lamotrigine for the first time in routine clinical practice, registered within 14 days of starting treatment, and followed for 1 year. The primary endpoint was time to recurrence/relapse of mood episodes after lamotrigine initiation, analyzed with Kaplan-Meier curves and log-rank testing.

Of 966 patients in the overall efficacy analysis set, 254 had bipolar I disorder and 643 had bipolar II disorder. For the comparison analyzed in this report, 191 patients with bipolar I disorder and 399 patients with bipolar II disorder were included because data were available for all patient characteristics examined.

Yes. More patients with bipolar II disorder started lamotrigine during a major depressive episode (78.7% vs 53.4%) and with moderate severity episodes (52.4% vs 41.4%). More patients with bipolar I disorder were receiving concomitant lithium (47.6% vs 26.3%), valproate sodium (25.1% vs 16.5%), and atypical antipsychotics (51.3% vs 31.6%), while concomitant antidepressant use was higher in bipolar II disorder (48.9% vs 28.8%).

No clear dose difference was reported between groups. The median daily dose of lamotrigine was 106.8 mg/d in bipolar I disorder and 136.2 mg/d in bipolar II disorder, and the authors stated that no differences in mean daily dose were observed between the groups.

Overall safety was similar in the two groups. Adverse drug reactions occurred in 22.0% of bipolar I patients (42/191) and 21.8% of bipolar II patients (87/399), with no significant difference in safety. Rash was the most frequently reported adverse drug reaction in both groups.

Skin disorders occurred in 11.5% of both groups: 22 of 191 patients with bipolar I disorder and 46 of 399 patients with bipolar II disorder. Serious skin disorders occurred in 0.5% of bipolar I patients (1/191) and 1.5% of bipolar II patients (6/399) and included rash, Stevens-Johnson syndrome, drug-induced hypersensitivity syndrome, erythema multiforme, and drug eruption. All patients recovered or were recovering except 1 bipolar I patient with rash of unknown outcome and 1 bipolar II patient with Stevens-Johnson syndrome with sequelae of visual impairment.

The main limitations are that this was a naturalistic observational study rather than a randomized controlled trial, with no control group and no blinding. The authors state that these features make it difficult to eliminate possible placebo effects, and patients were not registered consecutively, which could introduce sample selection bias. They also note that they cannot completely rule out the possibility that bipolar I patients were inherently at greater risk of recurrence than bipolar II patients.

The authors concluded that this study suggests lamotrigine may be more suitable for maintenance treatment in bipolar II disorder than in bipolar I disorder. They also stated that the findings support lamotrigine as a maintenance option not only in bipolar I disorder but also in bipolar II disorder, while emphasizing that the results come from a naturalistic study and should be interpreted with that limitation in mind.