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: 6.35). 08/2011; 50(8):749-62.e39. DOI: 10.1016/j.jaac.2011.05.011
Source: PubMed

ABSTRACT 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.

1 Follower
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The past 25 years has witnessed significant advances in our knowledge of Bipolar Spectrum Disorders (BPSD) in youth. Cross-sectional and longitudinal studies are clarifying the unique features of its pediatric presentation, including continuities and discontinuities across the spectrum of severity. Advances have been made, both in the pharmacological and psychological management of BPSD in youth. Current investigations may ultimately shed light on new treatment strategies. Future research is anticipated to be influenced by NIMH's Research Domain Criteria (RDoC). With this article, we summarize what is currently known about the basic phenomenology of pediatric BPSD, its clinical course, assessment and treatment, beginning with a summary of the major studies that have shed light on the topic. Next, we present a tally and content review of current research as an indicator of trends for the future. Then, we describe what we believe are important future directions for research. Finally, we conclude with implications for contemporary clinicians and researchers.
    Journal of Clinical Child & Adolescent Psychology 08/2013; DOI:10.1080/15374416.2013.817312 · 1.92 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Since little is known as to whether sex differences affect the clinical presentation of pediatric BP-I disorder, it is an area of high clinical, scientific and public health relevance. METHODS: Subjects are 239 BP-I probands (65 female probands, 174 male probands) and their 726 first-degree relatives, and 136 non-bipolar, non-ADHD control probands (37 female probands, 99 male probands) and their 411 first-degree relatives matched for age and sex. We modeled the psychiatric and cognitive outcomes as a function of BP-I status, sex, and the BP-I status-gender interaction. RESULTS: BP-I disorder was equally familial in both sexes. With the exception of duration of mania (shorter in females) and number of depressive episodes (more in females), there were no other meaningful differences between the sexes in clinical correlates of BP-I disorder. With the exception of a significant sex effect for panic disorder and a trend for substance use disorders (p=0.05) with female probands being at a higher risk than male probands, patterns of comorbidity were similar between the sexes. Despite the similarities, boys with BP-I disorder received more intensive and costly academic services than girls with the same disorder. LIMITATIONS: Since we studied children referred to a family study of bipolar disorder, our findings may not generalize to clinic settings. CONCLUSIONS: We found more similarities than differences between the sexes in the personal and familial correlates of BP-I disorder. Clinicians should consider bipolar disorder in the differential diagnosis of both boys and girls afflicted with symptoms suggestive of this disorder.
    Journal of Affective Disorders 02/2013; 149(1-3). DOI:10.1016/j.jad.2013.01.040 · 3.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Treatments for Pediatric Bipolar Disorder To the Editor: I read with interest the recent Journal article by Liu et al. 1 on pharmacologic treatments for pediatric bipolar disorder. I would like to note that two studies that were published within the time frame of 1989 to 2010 were, unfortunately, not included in the article. The first study is an open-label trial of lamotrigine in pediatric mania. 2 This study illustrated lamotrigi-ne's dosing strategies, the need for a slow upward titration, and the role of acute antipsychotics in the early phase of illness. The portal of entry for lam-otrigine use can be during acute illness, and the pharmacotherapy can then sustain symptom control. Also discussed were the optimization of its use in pediatric bipolar disorder and the mechanisms of the associated rash. Chang et al. 3 also published a lam-otrigine add-on study for depressive symptoms in pediatric bipolar disorder and reported decreases in manic, depressive, and aggressive symptoms. 3 The second study is a double-blinded random-ized trial that compared risperidone with dival-proex sodium. 4 The results suggested that risperi-done is associated with more rapid improvement and greater decrease in manic symptoms com-pared with divalproex sodium. In the context of deciphering the findings of clini-cal trials, regardless of the disorder, there appear to be several possibilities that remain unmentioned. There is a self-selection bias in placebo-controlled trials, in which a large proportion of parents do not consent for their children to participate; using rescue medications may mask the real efficacy of the study drug; un-treated comorbidities can interfere with the outcome ratings of the primary disorder; and highly specific side-effect profiles can potentially break the blind. These issues represent some of the imperfections of clinical trials, and they can skew evidence. Given the breadth and variance of pharmacologic studies, the periodic publication of evidence based on meta-analysis is necessary to offer the big picture of common trends. Liu et al. pro-vide us with such a welcome addition.
    Journal of the American Academy of Child and Adolescent Psychiatry 12/2011; 50(12):1290; author reply 1290-1. DOI:10.1016/j.jaac.2011.09.002 · 6.35 Impact Factor
Show more