Lamotrigine adjunct or monotherapy for the treatment of adolescents with bipolar depression.

Title
An open-label study of lamotrigine adjunct or monotherapy for the treatment of adolescents with bipolar depression.
Source
Journal of the American Academy of Child & Adolescent Psychiatry. 45(3):298-304, 2006 Mar.


OBJECTIVE:

The treatment of pediatric bipolar depression has not been well studied. The authors wished to prospectively study the efficacy of lamotrigine as adjunctive or monotherapy in adolescents with bipolar disorder who were experiencing a depressive episode.




Depressive symptoms commonly occur either as part of a first depressive mood episode or as part of a mixed episode. Four-year follow-up of a cohort of 86 youths with BD found that polarity switch into a depressive episode occurred 1.1 times per year. Suicidality appears at any given time in up to 25% of children with BD. Thus, effective and safe treatments for pediatric bipolar depression are greatly needed. SRIs have been reported through retrospective case reviews to cause or exacerbate manic symptoms in children and adolescents with BD. Most of these manic reactions occurred within 1 month of beginning antidepressant treatment. In this study, lamotrigine was an efficacious treatment for adolescents with bipolar depression without causing worsening of manic symptoms over the course of 2 months. Full resolution of depressive symptoms was seen as early as 1 month in 4 subjects and by 2 months in 11 of 19 subjects (58%), with effective doses ranging from 100 to 175 mg/day.

By gradual titration of lamotrigine and implementation of antigen precautions, the risk of serious rash may be largely minimized. This is in contrast to reports before 1998, in which children were commonly prescribed lamotrigine beginning at relatively high doses (e.g., 100 mg/day) and increasing the dose quickly. This quick titration may have led to the prior high rate of rash necessitating cessation of lamotrigine therapy. Current guidelines for children and adolescents, based on epilepsy data, recommend much more gradual titration, especially in the presence of adjunctive valproate therapy. Nevertheless, it is still recommended that any child or adolescent with a new rash appearing within the first 2 months of initiation or a dose increase of lamotrigine be evaluated, with probable subsequent discontinuation of lamotrigine therapy if there is no alternate reason for the rash. Most rashes caused by lamotrigine appear to be benign and resolve upon lamotrigine discontinuation. Any child with a serious rash, especially involving mucous membranes, should be immediately referred to an emergency treatment center for further treatment.



This is the first prospective trial of an agent for the treatment of adolescent bipolar depression. Given the robust efficacy of lamotrigine in adults with bipolar depression and these promising open data, further controlled studies should be conducted in this population as well as in younger children with bipolar depression.

CONCLUSIONS:

Adolescents with bipolar depression appeared to respond to lamotrigine treatment, whether as adjunctive therapy or monotherapy, with decreases in depression, mania, and aggression. Larger, placebo-controlled studies of lamotrigine are needed in this population.