Lamotrigine for BP II depression: Not FDA-Approved, but Likely Effective

January 31, 2011 · Posted in Potential Treatments 

At the 4th Biennial Conference of the International Society for Bipolar Disorders in Sao Paulo, Brazil in March, Jae Seung Chang of South Korea reported that in a year-long naturalistic, open label study of long-term adjunctive lamotrigine therapy in 109 patients with bipolar II depression, depression severity decreased when lamotrigine was added to patients’ regular treatment with mood stabilizers.


Interestingly, in addition to the data on lamotrigine, these investigators also found that having had a higher number of prior episodes was associated with a decreased response to lithium, a finding that has often been reported in the literature. Another finding was that a history that included a serious suicide attempt was associated with a decreased lamotrigine response.

Editor’s Note: The data on lamotrigine recall related findings by Mark Frye and Gabriela Obrocea in a study (in which this editor also participated) at the National Institute of Mental Health. In a six-week double-blind triple-crossover study between lamotrigine, gabapentin, and placebo, lamotrigine was more effective than gabapentin or placebo in reducing depression, as measured by Clinical Global Impression (CGI) scale scores.  In that study, a greater number of prior episodes was associated with decreased clinical responsiveness to lamotrigine.

Lamotrigine is only FDA-approved in bipolar I disorder for the prevention of depressed, manic and mixed episodes, and while it has some efficacy in preventing mania and mixed states, it is not effective in the acute treatment of mania.

Given this efficacy profile, lamotrigine (while not FDA approved for BP II disorder) appears to be a useful treatment option for BP II illness, where depressions are the central problem and hypomanias are typically of lesser concern.

Lamotrigine’s side effects are typically well-tolerated.  While the incidence of a severe rash in about 1 of 5,000 patients is a concern, very slow dose titration can prevent the emergence of this serious side effect, and lamotrigine does not cause weight gain, sexual dysfunction, or much sedation. This last is important since hypersomnia is a common presentation of BP II depression.


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