Korean J Psychopharmacol.  2008 Sep;19(5):276-282.

Lamotrigine Augmentation in Patients with Treatment-Resistant Major Depressive Disorder: A Naturalistic Study

  • 1Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Korea. kyooha@snu.ac.kr
  • 2Department of Psychiatry, Bugok National Hospital, Changnyeong, Korea.
  • 3Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, Seoul, Korea.


Lamotrigine's possible efficacy in the treatment of depressive disorders has been suggested. This naturalistic study investigated clinical response to lamotrigine augmentation in patients with treatment-resistant depression. Characteristics of the lamotrigine-responders were also explored.
Clinical data from 40 lamotrigine- treated patients with treatment-resistant unipolar depression were analyzed. The subjects were diagnosed with DSM-IV major depressive disorder and resistant to at least 2 antidepressants. Efficacy of lamotrigine treatment was measured by the changes in mean scores of the Clinical Global Impression Severity subscale (CGI-S), which were extracted from the prospective mood chart and structured interviews. Response was defined as a decrease of at least 2 or more from baseline on the CGI-S. Untoward effects associated with lamotrigine treatment were also assessed through medical records.
Significant reduction in the CGI-S mean score was observed from baseline through 8 week lamotrigine augmentation in 40 patients with treatment-resistant unipolar depression (t=5.7, df=39, p<.01), and the magnitude of treatment effect was large (r(effect size)=0.68). Drop-outs were mainly attributable to lamotrigine-associated rash (N=5). Greater rate of improvement was associated with responder group (N=14) compared to non-responder group (N=17) from week 3 onward.
The results of current study lend support to the potential benefit of lamotrigine augmentation in a subpopulation of patients with treatmentresistant unipolar depression. Continuation of lamotrigine add-on for more than 3 weeks may be needed to assess clinical outcome. Lamotrigine augmentation was generally well-tolerated. Large scale, double-blind studies are necessary to confirm its use as an augmentation agent.


Lamotrigine; Augmentation; Treatment-resistant depression
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