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Lamotrigine as an Augmentation Agent in Treatment-Resistant Depression

James G. Barbee, M.D., and Nowal J. Jamhour, M.A.


Background: The anticonvulsant lamotrigine has been reported to be efficacious and well tolerated as monotherapy in the treatment of bipolar patients as well as in treatment-refractory bipolar disorder. However, there is a paucity of research on the use of lamotrigine as an augmentation agent in treatment-refractory unipolar major depressive disorder.

Method: This study was a retrospective chart review on the efficacy of lamotrigine augmentation in 37 individuals diagnosed with chronic or recurrent major depressive disorder (DSM-IV) who had failed to respond adequately to at least 2 previous trials of antidepressants. Thirty-one patients who were on lamotrigine treatment for at least 6 weeks (6 discontinued prematurely due to adverse events) took a mean dose of 112.90 mg/day for a mean of 41.80 weeks. The primary efficacy parameter for this study was the Clinical Global Impressions scale, which was retrospectively applied. In addition, these data were supplemented by an analysis of prospectively rated Global Assessment of Functioning scores.

Results: On the basis of intent-to-treat analysis, response rates were as follows: 40.5% (15/37) much improved or very much improved, 21.6% (8/37) mildly improved, and 37.8% (14/37) unchanged. The percentage of patients who were rated much or very much improved and completed 6 weeks on the drug was 48.4% (15/31). No differences were found in the doses of lamotrigine given to responders and nonresponders.

Conclusion: Analyses revealed that lamotrigine treatment was most effective for patients who had been depressed for shorter periods of time and had failed fewer previous trials of antidepressants. Data also suggested a trend toward increased response for patients with comorbid anxiety disorders and/or chronic pain syndromes.

(J Clin Psychiatry 2002;63:737-741)


Received July 10, 2001; accepted Nov. 29, 2001. From the Department of Psychiatry, Louisiana State University Health Sciences Center, New Orleans.

Dr. Barbee has been a consultant for Wyeth, Pfizer, and Upjohn; has received grant/research support from Forest, GlaxoSmithKline, Pharmacia, Wyeth, Bristol-Myers, Pfizer, and SANO; and has been a member of the speakers' or advisory boards for GlaxoSmithKline, Lilly, Organon, Pfizer, and Wyeth. Mr. Jamhour reports no financial affiliation or other relationship relevant to the subject of this article.

Corresponding author and reprints: James G. Barbee, M.D., Department of Psychiatry, Louisiana State University Health Sciences Center, 1542 Tulane Ave., Box T4-6, New Orleans, LA 70122 (e-mail:jbarbe@lsuhsc.edu).