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

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.

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.

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.

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.