Melancholic Features in Bipolar Depression and Response to Lamotrigine: A Pooled Analysis of Five Randomized Placebo-Controlled Trials

BACKGROUND: A pilot study suggested lamotrigine may be more effective for bipolar depression with melancholic features. We tested this hypothesis in a pooled analysis of 5 randomized double-blind placebo-controlled trials of lamotrigine for acute bipolar depression. METHODS: The pooled sample consisted of 1072 adult outpatients. Depressive symptoms were assessed for 7 to 10 weeks with the Hamilton Depression Rating Scale and the Montgomery-Åsberg Depression Rating Scale. The outcome measure was end-trial response (score reduction ≥ 50%). Melancholic features were assessed with both the Structured Clinical Interview for DSM-IV and baseline depression scale items, according to DSM criteria. RESULTS: The item-based melancholic specifier was associated with numerically larger treatment effects, although subgroup-treatment interactions in logistic regression models did not reach statistical significance. The small subgroup of patients with severe psychomotor retardation also appeared to benefit from lamotrigine. However, the Structured Clinical Interview for DSM-IV melancholic specifier was not associated with larger treatment effects. Baseline depression severity was inconsistently associated with response, depending on which scale was used to define severity. The 2 melancholia variables had poor agreement despite having similar prevalences. CONCLUSIONS: Our results do not clearly support the original hypothesis but do reinforce the importance of replicating secondary analyses of clinical trials with additional data.