Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar depression: a multicenter, double-blind, placebo-controlled trial.

Objective: Lamotrigine is one of the pharmacologic options for the treatment of bipolar depression but has only been studied as monotherapy. This study compared the acute effects of lamotrigine and placebo as add-on therapy to ongoing treatment with lithium in patients with bipolar depression.
Method: Outpatients (N = 124) aged 18 years and older with a DSM-IV bipolar I or II disorder and a major depressive episode (Montgomery-Asberg Depression Rating Scale [MADRS] score > or = 18 and Clinical Global Impressions-Bipolar Version [CGI-BP] severity of depression score > or = 4) while receiving lithium treatment (0.6-1.2 mmol/L) were randomly assigned to 8 weeks of double-blind treatment with lamotrigine (titrated to 200 mg/d) or placebo. The primary outcome measure was mean change from baseline in total score on the MADRS at week 8. Secondary outcome measures were response (defined as a reduction of > or = 50% on the MADRS and/or change of depression score on the CGI-BP of "much improved" or "very much improved" compared to baseline) and switch to mania or hypomania (defined as a CGI-BP severity of mania score of at least mildly ill at any visit). Patients were included in the study between August 2002 (Spain started in October 2003) and May 2005.
Results: Endpoint mean change from baseline MADRS total score was -15.38 (SE = 1.32) points for lamotrigine and -11.03 (SE = 1.36) points for placebo (t = -2.29, df = 104, p = .024). Significantly more patients responded to lamotrigine than to placebo on the MADRS (51.6% vs. 31.7%, p = .030), but not on the CGI-BP change of depression (64.1% vs. 49.2%, p = .105). Switch to mania or hypomania occurred in 5 patients (7.8%) receiving lamotrigine and 2 patients (3.3%) receiving placebo (p = .441).
Conclusion: Lamotrigine was found effective and safe as add-on treatment to lithium in the acute treatment of bipolar depression.
Trial Registration: clinicaltrials.gov Identifier: NCT00224510.
(Copyright 2009 Physicians Postgraduate Press, Inc.)