Melancholic Symptoms in Bipolar II Depression and Responsiveness to Lamotrigine in an Exploratory Pilot Study.

Background: In this exploratory pilot study we reanalyzed data from a previous randomized, double-blind, placebo-controlled trial of lamotrigine for bipolar II depression in which lamotrigine was not superior to placebo to determine if splitting the sample into melancholic and nonmelancholic subgroups revealed a significant treatment effect.

Methods: Adult outpatients (n = 150) in an acute bipolar II depressive episode completed 8 weeks of treatment with lamotrigine (titrated to 200 mg/d) or placebo. Depressive symptoms were assessed at baseline and weekly with the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Montgomery-Åsberg Depression Rating Scale (MADRS). The presence of melancholic depression was determined by baseline responses to the HAMD-17 and MADRS according to the Diagnostic and Statistical Manual of Mental Disorders criteria. Cox regression models stratified by melancholic status were used to predict HAMD-17 and MADRS treatment response. Analysis-of-variance models were used to compare HAMD-17 and MADRS change scores between lamotrigine and placebo groups while testing for interactions by melancholic status.

Results: Lamotrigine was associated with higher odds of treatment response compared with placebo in the melancholic subgroup but not in the nonmelancholic subgroup. However, the melancholic subgroup-treatment interactions from the analysis-of-variance models were nonsignificant.

Conclusions: Further research is warranted to test the hypothesis that bipolar depression with melancholic symptoms is more responsive to lamotrigine over placebo than nonmelancholic bipolar depression.