31.12b Early-Onset Bipolar Disorder
1241
a greater likelihood is seen of mixed states and rapid cycling,
and higher rates of polarity changes compared with those who
develop bipolar disorders in late adolescence or early adulthood.
Treatment
Treatment of early onset bipolar disorder incorporates multi-
modal interventions including pharmacotherapy, psychoeduca-
tion, psychosocial intervention with the family and the child,
and school interventions to optimize a child’s school adjustment
and achievement.
Pharmacotherapy
Two classes of medications—atypical antipsychotics and mood
stabilizing agents—are the most well-studied agents that pro-
vide efficacy in the treatment of early-onset bipolar disorders.
Eight randomized controlled trials have shown efficacy of atypi-
cal antipsychotic agents in the treatment of bipolar disorder
in youth between the ages of 10 and 17 years. These studies
compared an atypical antipsychotic to placebo, or compared an
atypical antipsychotic to a mood stabilizer, or added an anti-
psychotic to a mood-stabilizing agent. The atypical antipsychot-
ics included olanzapine, quetiapine, risperidone, aripiprazole,
and ziprasidone. All five of the atypical antipsychotic stud-
ies demonstrated significant efficacy in the treatment of early
onset bipolar manic or mixed states. A recent trial comparing
quetiapine and valproate found that both were efficacious, but
the quetiapine was superior in the speed of its effect. In another
trial comparing risperidone and divalproex treatment for bipolar
disorder in youth, risperidone was found to have a more rapid
improvement and a greater final reduction in manic symptoms
compared to divalproex.
Mood-stabilizing agents have been used in open trials and
anecdotally with early onset bipolar illness with little evidence of
efficacy at this time. In trials using lithium or divalproex for treat-
ment of early onset bipolar disorder, responses were less robust
compared to results with atypical antipsychotics. Controlled
trials have provided some evidence suggesting that lithium is
efficacious in the management of aggression behavior disorders.
Although lithium has been approved for use in adolescent mania,
more research is needed to know if lithium is effective for more
classic forms of mania in adolescents. The Collaborative Lith-
ium Trials (CoLT) established a set of protocols to establish the
safety and potential efficacy of lithium in youth, and to develop
studies to provide evidence-based dosing of lithium for youth.
A group of researchers recently studied the first-dose pharma-
cokinetics of lithium carbonate in youth and found that clear-
ance and volume are correlated with total body weight in youth,
and particularly with fat-free mass. Difference in body size was
consistent with the pharmacokinetics of lithium metabolism in
children and adults. An open-label trial of lamotrigine (Lamictal)
in the treatment of bipolar depression among youth provides pos-
sible support for its use in children and adolescents.
Current evidence suggests a faster response and more robust
effect with atypical antipsychotics compared to mood-stabiliz-
ing agents in the treatment of early-onset bipolar disorder. How-
ever, given the severity and impairment of bipolar disorder in
youth, when only partial recovery is achieved, consideration of
adding an additional agent may be necessary.
Psychosocial Treatment
Psychosocial treatment interventions for early onset bipolar ill-
ness have included a family-focused treatment. This treatment
consists of several sessions of psychoeducation, then sessions
focusing on current stressors and mood management plan, and
then several sessions of communication enhancement train-
ing and problem-solving skills training. The use of this type
of intervention for youth diagnosed with bipolar disorder as
well as youth at risk for the disorder by virtue of their family
history or subthreshold conditions has been of value. Adjunc-
tive family-focused psychoeducational treatment modified for
children and adolescents has been shown to reduce relapse rate.
Children and adolescents treated with mood-stabilizing agents
in addition to a psychosocial intervention showed improvement
in depressive symptoms, manic symptoms, and behavioral dis-
turbance over 1 year.
A year-long trial of a modified Family Focused Treatment-
High Risk in youth with bipolar disorder showed significant
improvement in mood disturbance, especially depressive mood
and hypomania, and improved psychosocial functioning. Fam-
ily-focused treatment for high-risk youth is a promising inter-
vention that deserves further investigation as a longitudinal
follow-up to determine the course of youth at risk to develop
bipolar disorder.
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