Lamotrigine vs. lamotrigine plus divalproex in randomized, placebo-controlled maintenance treatment for bipolar depression

Abstract

Objective: To compare the maintenance efficacy of lamotrigine (Lam) to combination therapy of Lam+divalproex ER (Div) in recently depressed patients with bipolar disorder (BD).

Method: We randomized 86 BD I or II patients in a major depressive episode to 8 months of double-blind treatment with Lam+placebo or Lam+Div. To be eligible for randomization, patients had to achieve control of both depressive and manic symptoms during an open phase that included both Lam and Div.

Results: Time to depressive episode did not differ significantly by Kaplan-Maier survival analysis (χ2=1.82, df=1, P=0.18). However, several secondary outcomes did show significant differences. The proportion of Lam+placebo patients who had at least one Montgomery-Asberg Depression Rating Scale (MADRS) score≥15 during the maintenance phase was 67% (30/45) compared with 44% (18/41) for the Lam+Div group (χ2=4.51, P=0.03). Among BD I patients assigned to Lam+placebo, 71.4% (25/35) had at least one visit with MADRS score≥15 compared with 36.7% (11/30) among Lam+Div patients (χ2=7.89, df=1, P=0.005).

Conclusion: Lam+Div generally provided greater maintenance efficacy than Lam alone for depressive indices in recently depressed BD patients.