The research described in this manuscript was funded by GlaxoSmithKline. JRC has received grant research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Otsuka, the Cleveland Foundation, the Department of Defense, Eli Lilly & Co., GlaxoSmithKline, the Health Resources Services Administration, Janssen, Merck, the National Alliance for Research in Schizophrenia and Affective Disorders, the National Institute of Mental Health, Pfizer, the Stanley Medical Research Institute, and Wyeth; and has served as a consultant to or on the advisory boards of Abbott, AstraZeneca, Bristol-Myers Squibb, Otsuka, Eli Lilly & Co., GlaxoSmithKline, Janssen, Servier, Solvay/Wyeth and Teva. RFH, RLW, SE, TRT, JAA, ETM and RAL are employees of GlaxoSmithKline.
Lamotrigine in the acute treatment of bipolar depression: results of five double-blind, placebo-controlled clinical trials
Article first published online: 6 FEB 2008
© 2008 Blackwell Munksgaard
Volume 10, Issue 2, pages 323–333, March 2008
How to Cite
Calabrese, J. R., Huffman, R. F., White, R. L., Edwards, S., Thompson, T. R., Ascher, J. A., Monaghan, E. T. and Leadbetter, R. A. (2008), Lamotrigine in the acute treatment of bipolar depression: results of five double-blind, placebo-controlled clinical trials. Bipolar Disorders, 10: 323–333. doi: 10.1111/j.1399-5618.2007.00500.x
- Issue published online: 6 FEB 2008
- Article first published online: 6 FEB 2008
- Received 1 September 2006, revised and accepted for publication 13 February 2007
- bipolar depression;
- bipolar disorder;
Objectives: The efficacy of lamotrigine as maintenance treatment for bipolar disorder (BD), particularly for delaying depressive episodes, is well established, but its efficacy in the acute treatment of bipolar depression is less clear. This paper reports the results of five randomized, double-blind, placebo-controlled trials of lamotrigine monotherapy for the acute treatment of bipolar depression.
Methods: Adult subjects with bipolar I or II disorder experiencing a depressive episode were randomized to placebo or lamotrigine monotherapy (after titration, at a fixed dose of 50 mg or 200 mg daily in Study 1; a flexible dose of 100–400 mg daily in Study 2; or a fixed dose of 200 mg daily in Studies 3, 4 and 5) for 7–10 weeks.
Results: Lamotrigine did not differ significantly from placebo on primary efficacy endpoints [17-item Hamilton Depression Rating Scale in Studies 1 and 2; Montgomery–Asberg Depression Rating Scale (MADRS) in Studies 3, 4 and 5]. In Study 1, lamotrigine significantly separated from placebo on some secondary measures of efficacy, including the MADRS, the Clinical Global Impressions-Severity (CGI-S) and the CGI-Improvement (CGI-I), but seldom differed on secondary efficacy endpoints for the other studies.
Conclusions: Lamotrigine monotherapy did not demonstrate efficacy in the acute treatment of bipolar depression in four out of five placebo-controlled clinical studies. Lamotrigine was well tolerated in the acute treatment of bipolar depression.