Pharmacologic Treatments for Pediatric Bipolar Disorder: A Review and Meta-Analysis

University of Nebraska Medical Center, Omaha, USA.
Journal of the American Academy of Child and Adolescent Psychiatry (Impact Factor: 7.26). 08/2011; 50(8):749-62.e39. DOI: 10.1016/j.jaac.2011.05.011
Source: PubMed


A growing body of literature has documented pediatric bipolar disorder to be a severely impairing form of psychopathology. However, concerns remain as to the inadequacy of the extant literature on its pharmacotherapy. Furthermore, treatment studies have not been systematically reviewed for treatment effects on core and associated symptoms. Thus, a systematic evaluation and synthesis of the available literature on the efficacy of antimanic pharmacotherapy for pediatric bipolar disorder on symptoms of mania, depression, and attention-deficit/hyperactivity disorder was undertaken.
A systematic search was conducted through PubMed from 1989 through 2010 for open-label and randomized controlled trials published in English on the pharmacotherapy of pediatric mania.
There have been 46 open-label (n = 29) and randomized (n = 17) clinical trials of antimanic agents in pediatric bipolar disorder encompassing 2,666 subjects that evaluated a range of therapeutic agents, including traditional mood stabilizers, other anticonvulsants, second-generation antipsychotics, and naturopathic compounds. This literature has documented that the available armamentarium has different levels of efficacy in the treatment of pediatric mania. Because all psychotropic classes are associated with important adverse effects, a careful risk-benefit analysis is warranted when initiating pharmacologic treatment with any of these compounds. In the limited data available, the effects of antimanic agents on depression and symptoms of attention-deficit/hyperactivity disorder have been, in general, modest. Few studies have evaluated the effects of antimanic agents in children younger than 10 years.
A substantial body of scientific literature has evaluated the safety and efficacy of various medicines and drug classes in the treatment of mania in pediatric bipolar disorder. More work is needed to assess the safety and efficacy of psychotropic drugs in children younger than 10 years, to further evaluate the efficacy of naturopathic compounds, and to further evaluate the effects of antimanic treatments for the management of depression and attention-deficit/hyperactivity disorder.

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    • "Data are emerging from multiple large cross-sectional and longitudinal studies. Most influential are the ''EDSP-Bavarian Catchment'' study (Beesdo et al., 2009), the Course of Bipolar Youth study (Birmaher et al., 2006), the ''Stanley'' study (Findling et al., 2005), the Longitudinal Assessment of Manic Symptoms study (Findling et al., 2010), the Prepubertal and Early Adolescent Bipolar Disorder study (Geller et al., 1998), the Oregon Adolescent Depression Project (Lewinsohn, Klein, & Seeley, 1995), the ''Boston'' study (Wozniak et al., 2011), and the Assessing Bipolar Disorder: A Community-Academic Blend study (Youngstrom et al., 2005). Table 1 provides an overview of these studies' methodologies. "
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    Journal of Clinical Child & Adolescent Psychology 08/2013; 42(5). DOI:10.1080/15374416.2013.817312 · 1.92 Impact Factor
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    • "Family and other studies document robust patterns of familiality (Schulze et al., 2006, Wozniak et al., 2010, Wozniak et al., 2012), a protracted course (Wozniak et al., 2011) and selective responsivity to antimanic agents (Smith et al., 2007, Correll et al., 2010, Liu et al., 2011). While it clearly affects both sexes, very few studies have addressed whether the sex of the proband influences the clinical presentation of pediatric bipolar disorder. "
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    • "Interestingly, these effects were absent in cre-positive GSK3βflox mice. This observation is concordant with recent data showing an antidepressant-like effect of lentiviral vectors expressing siRNA targeted against GSK3β transcripts in the hippocampal dentate gyrus of stressed mice using these same behavioural paradigms [74]. Therefore, it seems possible that the overall antidepressant-like effects of systemic GSK3β inhibition can be explained, at least in part, by an inhibition of this kinase in the dentate gyrus. "
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