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

Acta Psychiatr Scand. 2012 Nov;126(5):342-50. doi: 10.1111/j.1600-0447.2012.01890.x. Epub 2012 Jun 18.


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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antimanic Agents / therapeutic use*
  • Bipolar Disorder / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lamotrigine
  • Male
  • Middle Aged
  • Treatment Outcome
  • Triazines / therapeutic use*
  • Valproic Acid / therapeutic use*


  • Antimanic Agents
  • Triazines
  • Valproic Acid
  • Lamotrigine