Treatment Of Pediatric Bipolar Disorder Research Articles

Evidence-based Psychopharmacological Treatments for Pediatric Bipolar Disorder

Evidence-based Psychopharmacological Treatments for Pediatric Bipolar Disorder

Assessing change in suicidal ideation intensity for youth in treatment for pediatric bipolar disorder.

Suicidal ideation (SI) is significantly higher for youth with pediatric bipolar disorder (PBD), yet clinical correlates of suicidality remain poorly understood in this population. The current study investigates how change in risk factors for SI relate to change in SI intensity over a 6-month period of treatment. Children ages 9 to 13 (N = 71; 41% female; 54% Caucasian; Mean age = 9.17) engaged in one of two psychotherapy treatment conditions and completed assessments of SI risk factors and psychopathology symptoms at baseline (pre-treatment), 4 and 8 weeks (during treatment), 12 weeks (post-treatment), and 39 weeks (follow-up assessment at 6 months post-treatment). Children also completed assessments of SI intensity at baseline, post-treatment (12 weeks), and 6 months post-treatment. Mixed-effects regression models indicate that increases in health-related quality of life in the family, mobilization of the family to acquire/accept help for PBD, and child self-concept were associated with decreased SI intensity over time. Findings highlight the importance of family and child level factors in influencing longitudinal change in SI intensity in youth with PBD. Clinical implications and future directions are discussed.

More than medication: The importance of family treatments for pediatric bipolar disorder

Pediatric bipolar disorder (PBD) is a chronic and debilitating illness characterized by episodic mood disturbance (e.g., extreme irritability, euphoria, and/or depression), accompanying symptoms (e.g., energy shifts, sleep disruption, cognitive disturbance of self/abilities, suicidality), high rates of comorbidities, and considerable functional impairment. Although PBD has biological underpinnings, cognitive, behavioral, and environmental stressors can trigger or exacerbate depressive and manic symptoms. Thus, while pharmacotherapy is effective for controlling biological contributions to mood episodes, psychotherapy is also necessary to target psychosocial factors that may activate or worsen symptoms in PBD, and to address associated academic, interpersonal, and functional impairment.

Using Lithium in Children and Adolescents with Bipolar Disorder: Efficacy, Tolerability, and Practical Considerations.

Lithium has been an intriguing treatment option in psychiatry for over a century. While seemingly just a simple elemental compound, it has powerful treatment effects for both depression and bipolar disorder. The evidence base for treatment of pediatric bipolar disorder is relatively small, but, in recent years, additional clinical trial data have enabled lithium to re-emerge as a valuable and, in many cases, preferred treatment. Pharmacologically, lithium is complex, with varied effects at both intracellular and extracellular levels. As a treatment for bipolar disorder in pediatrics, lithium is challenging, given its narrow therapeutic window and myriad of potential side effects. However, the efficacy of lithium continues to match that of newer pharmacologic agents, and its tolerability has been shown to be comparable with more commonly prescribed medications. Lithium is still one of few drugs that have been proven to reduce the risk of suicidality, and it may have utility in illnesses beyond affective disorders. Practically, as a primary agent or as an adjunct, lithium continues to claim a rightful place in the treatment armamentarium of child psychiatry. New dosing paradigms have improved tolerability and reduced potential side effects. Recent evidence affirms that lithium is effective for pediatric bipolar disorder in multiple phases of the illness.

Improving the Diagnosis and Treatment of Pediatric Bipolar Disorder

Awareness of the prevalence and impact of bipolar disorder in pediatric patients has grown in recent years. Youths with this disorder are at risk for poor long-term outcomes, but with careful screening, clinicians may be able to detect early signs or subthreshold symptoms and provide a timely diagnosis and effective treatment. Although several pharmacologic options are available for patients aged 10 years and up, they differ in their safety and tolerability profiles. Clinicians should select the agent that best balances benefit and risk-at the lowest efficacious dose-and provide careful monitoring for adverse events throughout treatment.

Early-Onset Bipolar Disorder: Characteristics and Outcomes in the Clinic.

To assess patient characteristics and clinician-rated outcomes for children diagnosed with early-onset bipolar disorder in comparison to a depressive disorders cohort from a single clinic site. To assess predictors of bipolar treatment response. Medical records from 714 consecutive pediatric patients evaluated and treated at an academic tertiary child and adolescent psychiatry clinic between 2006 and 2012 were reviewed. Charts of bipolar children (n = 49) and children with depressive disorders (n = 58) meeting study inclusion/exclusion criteria were compared on variables assessing clinical characteristics, treatments, and outcomes. Outcomes were assessed by using pre- and post-Clinical Global Impressions (CGI)-Severity and Children's Global Assessment Scale (CGAS) scores, and a CGI-Improvement score ≤2 at final visit determined responder status. Bipolar outcome predictors were assessed by using multiple linear regression. Clinic prevalence rates were 6.9% for early-onset bipolar disorder and 1.5% for very early-onset bipolar disorder. High rates of comorbid diagnoses, symptom severity, parental stress, and child high-risk behaviors were found in both groups. The bipolar cohort had higher rates of aggression and higher lifetime systems of care utilization. The final CGI and CGAS outcomes for unipolar depression patients differed statistically significantly from those for the bipolar cohort, reflecting better clinical status and more improvement at outcome for the depression patients. Both parent-reported Child Behavior Checklist total T-score at clinic admission and the number of lifetime systems-of-care for the child were significantly and inversely associated with improvement for the bipolar cohort. Early-onset bipolar disorder is a complex and heterogeneous psychiatric disorder. Evidence-based treatment should emphasize psychopharmacology with adjunctive family and individual psychotherapy. Strategies to improve engagement in treatment may be especially important. Given high rates of high-risk behaviors in these youth, regular mental health follow-up to assess safety is important. Additional evidence-based treatments for pediatric bipolar disorder are needed.

Infections and Childhood Psychiatric Disorders: Tick-Borne Illness and Bipolar Disorder in Youth

Objective: To explore possible links between tick-borne illness (TBI) and pediatric bipolar disorder (PBD) in a retrospective series of youth from a Northeast U.S. psychiatric private practice. Methods: PBD diagnosis in 27 youth (15 Bipolar I and 12 Bipolar II) was based on DSM-IV TR criteria following interviews with parents and children, questionnaires and school reports. Testing for Borrelia burgdorferi (Lyme disease), Babesia, Bartonella, Mycoplasma pneumoniae, Anaplasma and Ehrlichia occurred between February 2013 and July 2015. Lyme testing included an ELISA and Western Blot IgM/IgG and cultures; Babesia and Bartonella were ascertained by IgM/IgG antibody titers and fluorescent in-situ hybridization (FISH) tests. Other pathogen exposure was determined by IgM/IgG antibody titers. Testing was performed at LabCorp, Mayo Medical, IgeneX, Advanced Labs and/or Galaxy Diagnostics Laboratories. Clinical diagnoses were confirmed by physicians familiar with TBI. Data was summarized using descriptive statistics. Results: Eighty-one percent of the sample was male and 19% was female. Mean age at PBD diagnosis was 7.3 years. Exposure to one or more pathogens was found in 24/27 (89%) of the patients. Frequency of positive serology included: Babesia (n=16), Mycoplasma pneumoniae (n=11), Bartonella (N=8), and Lyme (n=6). Twenty-two of these 24 agreed to clinical evaluation and 92% (20/22) were diagnosed with TBI. Conclusion: The high rate of TBI in PBD patients presented here is provocative. If confirmed, this association may suggest gene-environment interactions and has implications for the prevention and treatment of PBD. Research evaluating TBI in bipolar cases vs. matched controls with other psychopathology and without psychiatric disease using standardized serological testing is needed.

Evidence-Based Pharmacologic Treatment of Pediatric Bipolar Disorder.

Pharmacotherapy is an important component of treatment for children and adolescents with bipolar disorder. The body of evidence supporting safe and effective treatments in this population is growing. Available data provide information on the risks and benefits of pharmacologic agents used for acute manic, mixed, and depressive episodes as well as for maintenance treatment. Lithium, anticonvulsants, and antipsychotics comprise the armamentarium for treating pediatric bipolar disorder. When selecting treatment, clinicians must consider the efficacy and side effect profile of potential pharmacotherapies, as well as the patient's history, including the presence of comorbidities, in order to develop a treatment plan that will ensure optimal outcomes.

Mediators in the randomized trial of Child- and Family-Focused Cognitive-Behavioral Therapy for pediatric bipolar disorder

Mediation analyses can identify mechanisms of change in Cognitive-Behavioral Therapy (CBT). However, few studies have analyzed mediators of CBT for youth internalizing disorders; only one trial evaluated treatment mechanisms for youth with mixed mood diagnoses. This study evaluated mediators in the randomized trial of Child- and Family-Focused CBT (CFF-CBT) versus Treatment As Usual (TAU) for pediatric bipolar disorder (PBD), adjunctive to pharmacotherapy. Sixty-nine children ages 7–13 with PBD were randomly assigned to CFF-CBT or TAU. Primary outcomes (child mood, functioning) and candidate mediators (family functioning, parent/child coping) were assessed at baseline and 4-, 8-, 12- (post-treatment), and 39-weeks (follow-up). Compared with TAU, children receiving CFF-CBT exhibited greater improvement in mania, depression, and global functioning. Several parent and family factors significantly improved in response to CFF-CBT versus TAU, and were associated with the CFF-CBT treatment effect. Specifically, parenting skills and coping, family flexibility, and family positive reframing showed promise as mediators of child mood symptoms and global functioning. Main or mediating effects for youth coping were not significant. CFF-CBT may impact children's mood and functioning by improving parenting skills and coping, family flexibility, and family positive reframing. Findings highlight the importance of parent coping and family functioning in the treatment of PBD.

Long-Term Treatment Strategies for Pediatric Bipolar Disorder

Bipolar disorder is a serious psychiatric disorder that frequently begins in childhood and lasts a lifetime. In the last 10–15 years, many advances have been made in the short-term treatment of bipolar disorder in children and adolescents, especially mixed and manic episodes. Less is known about long-term treatment and treatment of depressive episodes. This paper reviews recent literature on long-term treatment strategies for pediatric bipolar disorder. Pharmacologically, several second generation antipsychotics and mood stabilizers were recently studied in long-term treatment trials. These agents showed comparable effectiveness in reducing manic symptoms. Most benefits were attained early in treatment. The majority of patients did not complete the studies. The agents varied in their side effect profiles. Based on these findings, we recommend (1) maximizing treatment benefits during acute phase, (2) choosing a pharmacological agent on the basis of side effect profile, and (3) using the lowest effective dose to minimize side effect burden. Despite the benefits of medications, a majority of patients will not adhere to permanent medication regimen. Thus, psychosocial treatments can theoretically fill the gap and complement pharmacological treatments. No definitive psychosocial treatment for pediatric bipolar disorder has been developed. However, psychosocial treatments can facilitate medication adherence and early symptom recognition through psychoeducation. Dialectical Behavioral Therapy can assist with emotional regulation and reduce suicidality, and cognitive behavioral therapy can improve adherence and satisfaction with treatment.

Asenapine for the Acute Treatment of Pediatric Manic or Mixed Episode of Bipolar I Disorder

To evaluate asenapine versus placebo in 403 patients aged 10 to 17 years with bipolar I disorder currently in manic or mixed episodes. In this double-blind, placebo-controlled, international trial, patients were randomized 1:1:1:1 to placebo, asenapine 2.5, 5, or 10 mg b.i.d. (twice daily). Primary efficacymeasure was change from baseline in Young-Mania Rating Scale (YMRS) total score at day 21. Analyses of patients with/without attention-deficit/hyperactivity disorder (ADHD) and with/without stimulant use were performed. The mean difference in asenapine versus placebo in YMRS was -3.2 (p= .0008), -5.3 (p< .001), and -6.2 (p<.001) for asenapine 2.5, 5, and 10 mg b.i.d., respectively. Treatment-emergent adverse events with an incidence ≥5% and at least twice placebo were somnolence, sedation, hypoesthesia oral, paresthesia oral, and increased appetite. The asenapine groups had a higher incidence of≥7% weight gain (range, 8.0%-12.0%) versus placebo (1.1%; p< .05). The mean change from baseline in fasting insulin was larger for patients treated with asenapine thanthose with placebo (asenapine 2.5 mg b.i.d.: 73.375 pmol/L; asenapine 5 mg b.i.d.: 114.042 pmol/L; asenapine 10 mg b.i.d.: 59.846 pmol/L; placebo: 3.690 pmol/L). The mean changes from baseline for lipid parameters and glucose were also larger in asenapine groups than in the placebo group. No safety differences were observed with respect to ADHD and stimulant use. All asenapine doses versus placebo were superior based on change in YMRS at day 21. Asenapine was generally well tolerated in patients aged 10 to 17 years with bipolar I disorder in manic or mixed states. Increases in weight and fasting insulin were associated with asenapine. Clinical trial registration information-Efficacy and Safety of Asenapine Treatment for Pediatric Bipolar Disorder; http://clinicaltrials.gov; NCT01244815.

Management of Bipolar Disorder in Children and Adolescents

Treatment options for bipolar disorder have been primarily studied in adults. However, there is a growing body of research of these treatments in youths with bipolar disorder. Despite this there is still a huge gap in clinical trials performed on adults and children and as this manuscript will show, extrapolating results of adult studies doesn't necessarily translate to successful treatment in youths. Furthermore, although medication is the cornerstone of treatment in children and adolescents with bipolar disorder, psychosocial interventions are of paramount importance. The current manuscript will review the empirical evidence available for both pharmacological and psychosocial treatment strategies. In addition, evidence for the use of medications in different stages of bipolar disorder, including acute manic and mixed states and bipolar depression is addressed. The use of combination therapy, the treatment of pediatric bipolar disorder comorbid with other psychiatric conditions and the management of treatment resistant mania is also discussed.

Differential Treatment of Pediatric Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder

This article offers a pragmatic model of conceptualizing attention deficit hyperactivity disorder and pediatric bipolar disorder when they present alone, together, or as overlapping subsyndromes. Evidence-based findings from the US Food and Drug Administration-approved medications and randomized controlled trials of psychotherapy are quilted together to design a personalized treatment model. The treatment paradigm consists of an “ABCD” model of components: (A) Assessment of psychopathology toward individual diagnosis or comorbidity, (B) Brain circuitry function offering explanatory power for the phenomenology that includes affective and cognitive domain difficulties common in both the disorders, (C) Chemical imbalance addressed through pharmacotherapy for mania, mixed mania, depression, and attention deficit hyperactivity disorder, and (D) Delivery of proven psychosocial treatment coupled with addressing the key dynamics of interpersonal relationships. This intervention, based on empirical findings, is applicable to clinical practice. Identifying the neurocircuitry of cognitive and emotional impairment in pediatric bipolar disorder and attention-deficit/hyperactivity disorder guides the application of targeted treatments: a paradigm of translating science to clinical service. [ Psychiatr Ann . 2014; 44(10):471–480.]

Practitioner review: Long-term pharmacological treatment of pediatric bipolar disorder.

Although long-term treatment is a core aspect of the management of children and adolescents with bipolar disorder (BD), most clinical recommendations are based on results from short-term studies or adult data. In order to guide clinical practice, we review the efficacy and safety profile of mood stabilizers, antipsychotics, and other pharmacological strategies for the long-term treatment of BD in pediatric patients. A MEDLINE, EMBASE, Cochrane and PsycInfo search (inception through November 2013) was performed to identify prospective studies longer than 12weeks assessing the use of pharmacological strategies for the long-term treatment of BD in pediatric patients (0-18years of age). Four randomized controlled trials (RCT) [three placebo-controlled (assessing aripiprazole (2) and flax oil), and one head-to-head comparison of lithium vs. divalproex], and thirteen noncontrolled studies (six open-label studies assessing lithium or anticonvulsants, five assessing second-generation antipsychotics (SGAs) and four assessing combination strategies) were included in the review. Aripiprazole has shown efficacy for relapse prevention in children with pediatric bipolar disorder (PBD) 4-9years of age in one placebo-controlled RCT. Positive results have been reported in noncontrolled studies with quetiapine and lithium for relapse prevention, as well as with lithium, quetiapine, ziprasidone, and the combination of risperidone and divalproex or lithium for long-term symptom reduction in PBD. The most frequently reported adverse events in children and adolescents treated with lithium and anticonvulsants are gastrointestinal and neurological, whereas use of SGAs is mainly related to weight gain and sedation. According to the limited empirical evidence, aripiprazole can be useful for relapse prevention in children with PBD. Given the lack of consistent efficacy data, clinical decision making should be based on individual clinical aspects and safety concerns.

Treatment of Pediatric Bipolar Disorder

Onceleri pediatrik bipolar bozukluk cok nadir gorulen bir psikiyatrik bozukluk olarak dusunulse de, son 20 yildaki arastirmalar bozuklugun sanilandan cok daha yaygin oldugunu ortaya koymustur. Cocuk ve ergenlik baslangicli bipolar bozukluk ciddi ailesel ve akademik sorunlara, daha sik madde kullanimina, riskli cinsel iliskilere, ergen gebeligi ve suca yatkinliga neden olmaktadir. Eriskin baslangicliya gore yasam boyu daha kotu bir islevsellik soz konusudur. Tani konulmasi daha guc olabilmekte ve tani konulana kadar gecen sure eriskin bipolar bozukluguna gore daha uzun olabilmektedir. Bu yas grubunun ozelliklerinden dolayi tedavi uyumu ile iliskili problemlere daha sik rastlanmaktadir. Pediatrik bipolar bozukluktaki bu tani ile ilgili karmasa, tedavi konusunda da anlasmazliklara yol acmistir. Bu gozden gecirmede cocuk ve ergenlik baslangicli bipolar bozukluktaki tedavi yaklasimlari ele alinmistir.

Pharmacotherapy of bipolar disorder in children and adolescents: an update

To review the options for acute and maintenance pharmacological treatment of bipolar disorder in children and adolescents, including the treatment of bipolar depression and comorbid attention deficit/hyperactivity disorder (ADHD). Narrative review of randomized clinical trials and open-label studies published from 2000 to 2012. The PubMed and PsycINFO websites were queried. Case series were included when a higher level of evidence was not available. Published data from randomized controlled trials (RCTs) in acute mania/hypomania with significant responses are available for lithium, topiramate, risperidone, olanzapine, and aripiprazole. Open trials of lithium and lamotrigine show that these drugs may be effective in the treatment of depressive episodes. No trials of selective serotonin reuptake inhibitors (SSRIs) have been conducted. In the treatment of comorbid ADHD, there are encouraging findings with mixed amphetamine salts and atomoxetine; conflicting results are observed with methylphenidate. Published RCTs of traditional mood stabilizers are scarce, but the best available evidence (results from meta-analytic regression) suggests that second-generation antipsychotics (SGAs) as a group are more effective in reducing manic symptoms. Risperidone was the only one included in head-to-head comparisons (vs. lithium and divalproex), showing superiority in terms of efficacy, but with more metabolic side effects, which were also more common in most of the SGAs. There are few studies addressing the treatment of ADHD and depression. Brazilian guidelines for the treatment of pediatric bipolar disorder should also include some SGAs (especially risperidone and aripiprazole) as first-line treatment, and these drugs should be provided by the public health services.

Post-Acute Effectiveness of Lithium in Pediatric Bipolar I Disorder

This study examined the long-term effectiveness of lithium for the treatment of pediatric bipolar disorder within the context of combination mood stabilizer therapy for refractory mania and pharmacological treatment of comorbid psychiatric conditions. Outpatients, ages 7-17 years, meeting American Psychiatric Association, diagnostic and statistical manual of mental disorders, 4th ed. (DSM-IV) diagnostic criteria for bipolar disorder I (BP-I) (manic or mixed) who demonstrated at least a partial response to 8 weeks of open-label treatment with lithium (phase I) were eligible to receive open-label lithium for an additional 16 weeks (phase II). Up to two adjunctive medications could be prescribed to patients experiencing residual symptoms of mania or comorbid psychiatric conditions, following a standardized algorithm. Forty-one patients received continued open-label long-term treatment with lithium for a mean of 14.9 (3.0) weeks during phase II. The mean weight-adjusted total daily dose at end of phase II was 27.8 (6.7) mg/kg/day, with an average lithium concentration of 1.0 (0.3) mEq/L. Twenty-five of the 41 patients (60.9%) were prescribed adjunctive psychotropic medications for residual symptoms. The most frequent indications for adjunctive medications were refractory mania (n=13; 31.7%) and attention-deficit/hyperactivity disorder (ADHD) (n=15; 36.6%). At the end of this phase 28 (68.3%) patients met a priori criteria for response (≥50% reduction from phase I baseline in young mania rating scale [YMRS] summary score and a clinical global impressions-improvement [CGI-I] score of 1 or 2), with 22 (53.7%) considered to be in remission (YMRS summary score≤12 and CGI-severity score of 1 or 2). These data suggest that patients who initially responded to lithium maintained mood stabilization during continuation treatment, but partial responders did not experience further improvement during Phase II, despite the opportunity to receive adjunctive medications. The most commonly reported (≥20%) adverse events associated with lithium treatment were vomiting, headache, abdominal pain, and tremor. Lithium may be a safe and effective longer-term treatment for patients with pediatric bipolar disorder who respond to acute treatment with lithium. Partial responders to acute lithium did not appear to experience substantial symptom improvement during the continuation phase, despite the possibility that adjunctive medications could be prescribed.

CoLT and TEAM: What Do the Results Tell Clinicians about Rational Treatment for Pediatric Bipolar Disorder?

Free AccessCoLT and TEAM: What Do the Results Tell Clinicians about Rational Treatment for Pediatric Bipolar Disorder?Helen Burton and Adelaide RobbHelen BurtonAddress correspondence via email to [email protected]Search for more papers by this author and Adelaide RobbChildren's National Medical Center.Address correspondence via email to [email protected]Search for more papers by this authorPublished Online:September 2012https://doi.org/10.1521/capn.2012.17.4.1PDFPDF PLUS ShareShare onFacebookTwitterLinkedInRedditEmail ToolsAdd to favoritesDownload CitationsTrack Citations About Next article FiguresReferencesRelatedDetails Cited byCited byJess Levy and Vijayabharathi Ekambaram1. New ResearchOnline publication date: 16 August 2016. Go to citation Crossref Volume 17Issue 4Aug 2012 Information© 2012 Guilford Publications Inc.PDF download

P-197 - Risperidone and divalproex influence brain function networks in pediatric mania

Introduction There is accumulating evidence for the efficacy and effectiveness of divalproex sodium (divalproex) and risperidone in the treatment of pediatric bipolar disorder (PBD). Objectives Clinical neuroimaging studies using appropriate challenge paradigms are a promising strategy for investigating how these medications influence brain function to provide therapeutic benefit. Aims Given that affect regulation is influenced by cognitive operations and vice versa, the current study of pediatric mania adopted a mechanistic orientation in comparing the action of two types of medications on brain function while engaged in memory operations, executive function, and response inhibition. Methods This was a double-blind 6-week fMRI trial with 24 unmedicated manic patients randomized to risperidone or divalproex, and 14 healthy controls (HCs) (mean age: 13.1 ± 3.3years). Response inhibition, affective N back, and affective colormatching fMRI tasks were completed pre- and post-treatment. Results Risperidone, a serotonin dopamine antagonist, impacted frontostriatal circuitry while divalproex, a mood stabilizer, worked on frontotemporal circuitry. This finding was replicated across paradigms. In conjunction, across medication types, increased VLPFC at baseline timepoint predicted better treatment outcome. Conversely, increased amygdala activity at baseline predicted poorer treatment outcome. Conclusions Our study demonstrated how the neural networks were engaged in PBD patients during both cognitive and affective paradigms and while under the influence of an SGA and an anti-epileptic. When risperidone and divalproex are directly compared, there was significantly greater engagement of the frontostriatal regions with risperidone and in the frontotemporal regions with divalproex across all tasks.

Translational neuroscience in pediatric bipolar disorder

Evaluation of: Pavuluri MN, Passarotti AM, Lu LH, Carbray JA, Sweeney JA. Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder: fMRI outcomes. Psychiatric Res. 193(1), 28–37 (2011).While controversial and often confounded with other forms of psychopathology, recent studies have shown that bipolar disorder (BD) is on the rise in children and adolescents. Research has made important strides in advancing our understanding of the phenomenology, neural underpinnings and treatment outcomes for BD youths. However, there is an increasing need to unite these domains to identify potential neural effects and predictors of treatment outcome. Pavuluri et al. have conducted such a study, evaluating the neural effects of divalproex or risperidone for pediatric BD. The future is likely to bring more of such studies, potentially resulting in a biomarker augmented approach to the diagnosis and treatment of pediatric BD.