Pharmacologic Treatments for Pediatric Bipolar Disorder: A Review and Meta-Analysis
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.
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ABSTRACT: Abstract Objective: Little is known regarding demographic and/or clinical characteristics associated with the use of lithium among adolescents with bipolar disorder (BP) in naturalistic clinical settings. We therefore examined factors associated with lithium among adolescents with BP presenting to a tertiary outpatient clinic. Methods: Participants were 100 adolescents 13-19 years of age, with BP-I, BP-II, or BP not otherwise specified (BP-NOS). Diagnoses and lifetime medication exposure were determined using the Schedule for Affective Disorders and Schizophrenia for School Age Children, Present and Lifetime Version (KSADS-PL). Analyses examined for demographic and clinical correlates of lifetime lithium exposure. Results: Twenty percent of participants reported lifetime lithium use. Participants with, versus those without, lifetime lithium use were significantly older and significantly more likely to have BP-I, lifetime history of psychiatric hospitalization, and psychosis. Lithium-treated participants were significantly more likely to report use of second-generation antipsychotics (SGAs) and antimanic anticonvulsants. In contrast, participants with lithium exposure were significantly less likely to have BP-II, self-injurious behavior, and a family history of depression. Adolescents with lithium exposure had significantly less parent-reported family conflict and mood lability, and significantly less self-reported impulsivity, emotional dysregulation, identity confusion, and interpersonal problems. In multivariable analyses, lithium use was associated with greater lifetime SGA use, lower parent-reported family conflict, and lower adolescent-reported interpersonal problems. Conclusions: Lithium was infrequently used among adolescents with BP in this sample. Although constrained by retrospective methodology and a single site, our findings suggest that clinicians may be deferring lithium use until late in treatment. The fact that there are lower rates of lithium use among adolescents with suicidal ideation, impulsivity, mood lability, and family history of depression suggests potential missed opportunities for use of lithium among high-risk adolescents with BP.Journal of Child and Adolescent Psychopharmacology 07/2014; 24(7). DOI:10.1089/cap.2013.0120 · 3.07 Impact Factor
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ABSTRACT: Dramatically increasing prevalence rates of bipolar disorder in children and adolescents in the United States have provoked controversy regarding the boundaries of manic symptoms in child and adolescent psychiatry. The serious impact of this ongoing debate on the treatment of affected children is reflected in the concomitant increase in prescription rates for antipsychotic medication. A key question in the debate is whether this increase in bipolar disorder in children and adolescents is based on a better detection of early-onset bipolar disorder-which can present differently in children and adolescents-or whether it is caused by an incorrect assignment of symptoms which overlap with other widely known disorders. So far, most findings suggest that the suspected symptoms, in particular chronic, non-episodic irritability (a mood symptom presenting with easy annoyance, temper tantrums and anger) do not constitute a developmental presentation of childhood bipolar disorder. Additional research based on prospective, longitudinal studies is needed to further clarify the developmental trajectories of bipolar disorder and the diagnostic status of chronic, non-episodic irritability.12/2014; 6:111. DOI:10.12703/P6-111
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ABSTRACT: Just like children are not small adults, pediatric studies are not just subgroup-adult studies. Clinical pharmacology aims to predict these effects based on drug, population and/or patient-specific pharmacokinetics (concentration-time profiles) and -dynamics (concentration-effect profile). The most essential characteristics of childhood are growth and maturation. Both phenomena are most prominent during infancy making the claim that "an infant is not just a small child" as relevant compared to the paradigm that "a child is not just a small adult". From a clinical pharmacology perspective, the consequence of such a dynamic setting is extensive variability throughout childhood in both the pharmacokinetics and pharmacodynamics. Trial design probably has impact on recruitment to an even greater extent compared to adult studies. In general, if a study is designed well, with a clear clinical question with which parents and children can identify, they are likely to consider participation. Open communication with all stakeholders involved will most likely result in ethically correct, practically feasible, scientifically sound, and economical reasonable studies to provide children with the appropriate treatment. From an academic perspective, feasibility, relevance, applicability and costs of clinical pharmacological studies in children can be significantly improved by new sampling concepts (e.g., saliva, urine, dried spot blood) and the systematic introduction of already known information into the trial design through model based pediatric drug development, that mainly affect feasibility of pharmacokinetic studies. In contrast, for the pharmacodynamic part of pediatric studies, development and validation of population specific biomarkers or robust outcome variables is urgently needed.08/2012; 1(2):3-7. DOI:10.5409/wjcp.v1.i2.3