Bipolar Disorder: Findling RL

McClellan J, Kowatch R, Findling RL, Anonymous00074. · AACAP Communications Department, Washington, DC 20016, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #17195735 No free full text.

Abstract: This practice parameter reviews the literature on the assessment and treatment of children and adolescents with bipolar disorder. The parameter focuses primarily on bipolar 1 disorder because that is the type most often studied in juveniles. The presentation of bipolar disorder in youth, especially children, is often considered atypical compared with that of the classic adult disorder, which is characterized by distinct phases of mania and depression. Children who receive a diagnosis of bipolar disorder in community settings typically present with rapid fluctuations in mood and behavior, often associated with comorbid attention-deficit/hyperactivity disorder and disruptive behavior disorders. Thus, at this time it is not clear whether the atypical forms of juvenile mania and the classic adult form of the disorder represent the same illness. The question of diagnostic continuity has important treatment and prognostic implications. Although more controlled trials are needed, mood stabilizers and atypical antipsychotic agents are generally considered the first line of treatment. Although patients may respond to monotherapy, combination pharmacotherapy is necessary for some youth. Behavioral and psychosocial therapies are also generally indicated for juvenile mania to address disruptive behavior problems and the impact of the illness on family and community functioning.

Kowatch RA, Fristad M, Birmaher B, Wagner KD, Findling RL, Hellander M, Anonymous00051. · Department of Psychiatry, Cincinnati Children's Hospital Medical, OH 45267-0559, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #15725966 No free full text.

Abstract: Clinicians who treat children and adolescents with bipolar disorder desperately need current treatment guidelines. These guidelines were developed by expert consensus and a review of the extant literature about the diagnosis and treatment of pediatric bipolar disorders. The four sections of these guidelines include diagnosis, comorbidity, acute treatment, and maintenance treatment. These guidelines are not intended to serve as an absolute standard of medical or psychological care but rather to serve as clinically useful guidelines for evaluation and treatment that can be used in the care of children and adolescents with bipolar disorder. These guidelines are subject to change as our evidence base increases and practice patterns evolve.

Mao AR, Findling RL. · No affiliation provided · Aust N Z J Psychiatry. · Pubmed #17620159 No free full text.

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Post RM, Chang KD, Findling RL, Geller B, Kowatch RA, Kutcher SP, Leverich GS. · No affiliation provided · J Clin Psychiatry. · Pubmed #15291676 No free full text.

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Demeter CA, Townsend LD, Wilson M, Findling RL. · Department of Psychiatry, University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, Ohio 44106-5080, USA. · Dialogues Clin Neurosci. · Pubmed #18689291 No free full text.

Abstract: Although recently more research has considered children with bipolar disorder than in the past, much controversy still surrounds the validity of the diagnosis. Furthermore, questions remain as to whether or not childhood expressions of bipolarity are continuous with adult manifestations of the illness. In order to advance current knowledge of bipolar disorders in children, researchers have begun to conduct phenomenological, longitudinal, treatment, and neuroimaging studies in youths who exhibit symptoms of bipolar illness, as well as offspring of parents with bipolar disorders. Regardless of the differences between research groups regarding how bipolar disorder in children is defined, it is agreed that pediatric bipolarity is a serious and pernicious illness. With early intervention during the period of time in which youths are exhibiting subsyndromal symptoms of pediatric bipolarity, it appears that the progression of the illness to the more malignant manifestation of the disorder may be avoided. This paper will review what is currently known and what still is left to learn about clinically salient topics that pertain to bipolar disorder in children and adolescents.

Townsend LD, Demeter CA, Wilson M, Findling RL. · Child and Adolescent Psychiatry, University Hospitals Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106-5080, USA. · Curr Psychiatry Rep. · Pubmed #18221635 No free full text.

Abstract: Children and adolescents with a bipolar disorder experience mood dysregulation that is often chronic with little interepisodic recovery. Although bipolar disorder in youth is recognized by more and more clinicians, much is still not known regarding how best to accurately diagnose and effectively treat it. As a result, children and adolescents with bipolar disorder are often symptomatic for long periods of time before receiving appropriate treatment. In this review of the pediatric bipolar disorder literature, the phenomenology, longitudinal course, and risk factors associated with the illness' development are discussed. Also, recent research pertaining to neuroimaging and pharmacologic and psychological treatments are considered. Because pediatric bipolar disorder is such a pernicious condition, it is recommended that clinicians complete a careful assessment of mood symptoms and comorbid conditions when this illness is suspected so that they can provide treatments with the best chance of benefit in a timely manner.

Youngstrom EA, Birmaher B, Findling RL. · Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3270, USA. · Bipolar Disord. · Pubmed #18199237 No free full text.

Abstract: OBJECTIVE: To find, review, and critically evaluate evidence pertaining to the phenomenology of pediatric bipolar disorder and its validity as a diagnosis. METHODS: The present qualitative review summarizes and synthesizes available evidence about the phenomenology of bipolar disorder (BD) in youths, including description of the diagnostic sensitivity and specificity of symptoms, clarification about rates of cycling and mixed states, and discussion about chronic versus episodic presentations of mood dysregulation. The validity of the diagnosis of BD in youths is also evaluated based on traditional criteria including associated demographic characteristics, family environmental features, genetic bases, longitudinal studies of youths at risk of developing BD as well as youths already manifesting symptoms on the bipolar spectrum, treatment studies and pharmacologic dissection, neurobiological findings (including morphological and functional data), and other related laboratory findings. Additional sections review impairment and quality of life, personality and temperamental correlates, the clinical utility of a bipolar diagnosis in youths, and the dimensional versus categorical distinction as it applies to mood disorder in youths. RESULTS: A schema for diagnosis of BD in youths is developed, including a review of different operational definitions of 'bipolar not otherwise specified.' Principal areas of disagreement appear to include the relative role of elated versus irritable mood in assessment, and also the limits of the extent of the bipolar spectrum--when do definitions become so broad that they are no longer describing 'bipolar' cases? CONCLUSIONS: In spite of these areas of disagreement, considerable evidence has amassed supporting the validity of the bipolar diagnosis in children and adolescents.

Azorin JM, Findling RL. · Hôpital de Sainte-Marguerite, Marseille, France. · CNS Drugs. · Pubmed #18020481 No free full text.

Abstract: This review aims to provide an update on valproate use in children and adolescents with bipolar disorder by summarising currently available clinical trials results. Guidelines for the treatment of type I bipolar disorder in children and adolescents, with or without psychotic features, recommend valproate, alone or in combination with an atypical antipsychotic, as a first-line treatment option; however, most randomised and open-label studies investigating valproate in paediatric populations have only evaluated a small number of participants. Therefore, the data from these studies need to be interpreted cautiously. A further complicating issue is the controversy surrounding the definition and diagnosis of bipolar disorders in this age group. Data suggest that valproate may be particularly useful for patients whose symptoms have not been responsive to lithium, or as part of combination therapy. Evidence from randomised controlled trials show that valproate monotherapy is associated with a Young Mania Rating Scale (YMRS) response rate (percentage of patients with a reduction in YMRS score from baseline to endpoint of >/=50%) of 53%, while combination therapy with valproate plus quetiapine is associated with a YMRS response rate of 87%; however, placebo response rates were high, emphasising the need for caution when interpreting data from open-label trials. At present, data supporting the efficacy and safety of mood stabilisers for the treatment of bipolar disorders in children and adolescents are limited; therefore, well designed, randomised controlled clinical studies are needed to identify and confirm the potential roles of valproate in children and adolescents with bipolar disorders, particularly in those with psychiatric co-morbidities. Furthermore, clinical studies are required to clarify the efficacy and tolerability profile of valproate in comparison with other agents used in paediatric and adolescent bipolar disorder.

Wilson MS, Findling RL. · Case Western Reserve University/University Hospitals Case Medical Center, Division of Child & Adolescent Psychiatry, Department of Psychiatry, 11100 Euclid Ave, Cleveland, OH 44106-5080, USA. · Expert Opin Pharmacother. · Pubmed #17163811 No free full text.

Abstract: In recent years, research into bipolar depression has increased. Each year, more studies are published using different agents to treat this condition. In addition to effectiveness and tolerability, bipolar depression research has sought agents that do not induce cycling or mania. This paper evaluates an open-label pilot study on zonisamide for bipolar depression that examined the effectiveness and tolerability of this agent while observing for any switch to mania. Zonisamide was found to have a very low switch rate and modest effectiveness. However, a high dropout rate was observed--mostly due to side effects. Until further research is available, zonisamide is not recommended as a first-line treatment for bipolar depression.

Smarty S, Findling RL. · Child and Adolescent Psychiatry, University Hospitals of Cleveland/Case Western Reserve University, 11100 Euclid Ave., Cleveland, OH 44106, USA. · Psychopharmacology (Berl). · Pubmed #17093980 No free full text.

Abstract: RATIONALE: Pediatric bipolar disorder (PBD) is a chronic and debilitating psychiatric illness. It is associated with many short-term and long-term complications including poor academic and social performance, legal problems and increased risk of suicide. Moreover, it is often complicated by other serious psychiatric disorders including attention deficit hyperactivity disorder, oppositional defiant disorder, conduct disorder and substance use disorders. For these reasons, there is a need for effective treatment for PBD. OBJECTIVES: To review available data from published reports of the treatment of PBD, highlighting those treatment practices for which there is scientific evidence. To suggest directions for future research. MATERIALS AND METHODS: A comprehensive Medline search was performed to identify published reports from 1995 to 2006. Reports with the greatest methodological stringency received greater focus. RESULTS: There is limited evidence from double-blind, placebo-controlled trials regarding the treatment of PBD. Available data suggests that lithium, some anticonvulsants and second-generation antipsychotics may be equally beneficial in the acute monotherapy for youth with mixed or manic states. However, because of limited response to acute monotherapy, there is increased justification for combination therapy. There is very limited data on the treatment of the depressed phase of bipolar illness in the youth. Also, very few studies have addressed the treatment of comorbidities and maintenance/relapse prevention in PBD. CONCLUSION: Although significant progress was made in the treatment of youth with bipolar disorder, there is a need for more methodologically stringent research to more precisely define evidence-based treatment strategies for PBD.

Youngstrom E, Meyers O, Youngstrom JK, Calabrese JR, Findling RL. · Department of Psychology, University of North Carolina, Chapel Hill, NC 27599, USA. · Dev Psychopathol. · Pubmed #17064426 No free full text.

Abstract: The goal of this paper is to review assessment research of bipolar disorder in children and adolescents. The review addresses numerous themes: the benefits and costs of involving clinical judgment in the diagnostic process, particularly with regard to diagnosis and mood severity ratings; the validity of parent, teacher, and youth self-report of manic symptoms; how much cross-situational consistency is typically shown in mood and behavior; the extent to which a parent's mental health status influences their report of child behavior; how different measures compare in terms of detecting bipolar disorder, the challenges in comparing the performance of measures across research groups, and the leading candidates for research or clinical use; evidence-based strategies for interpreting measures as diagnostic aids; how test performance changes when a test is used in a new setting and what implications this has for research samples as well as clinical practice; the role of family history of mood disorder within an assessment framework; and the implications of assessment research for the understanding of phenomenology of bipolar disorder from a developmental framework.

Kowatch RA, Youngstrom EA, Danielyan A, Findling RL. · Department of Psychiatry, Cincinnati Children's Hospital Medical Center/University of Cincinnati Medical Center, Cincinnati, OH 45267, USA. · Bipolar Disord. · Pubmed #16403174 No free full text.

Abstract: OBJECTIVE: Using predetermined criteria for study quality and methods, a literature review and meta-analysis of seven reports about pediatric bipolar disorder (BPD) was conducted to determine if there is a consistent picture of the phenomenology and clinical characteristics of BPD in children and adolescents. METHODS: Searches were conducted in MedLine and PsycINFO using the terms mania, BPD, children and adolescents, and was limited to published articles in peer-reviewed journals. Seven reports were selected that met the following criteria: a systematic method for the elicitation and reporting of symptoms and clinical characteristics of subjects; subjects were interviewed by a trained researcher or clinician; ages 5-18 years; use of a diagnostic system, either DSM or RDC for categorization; a consensus method for the establishment of the diagnosis of BPD. RESULTS: Most DSM-IV symptoms of mania were common in the children and adolescents with BPD with the most common symptoms being increased energy, distractibility, and pressured speech. On average, four of five bipolar cases also showed threshold levels of irritable mood and grandiosity, and more than 70% of all cases showed elated/euphoric mood, decreased need for sleep, or racing thoughts. Roughly 69% of cases also showed poor judgment, whereas only half of bipolar cases demonstrated flight of ideas, and slightly more than one-third showed hypersexuality or psychotic features. CONCLUSIONS: The clinical picture that emerges is that of children or adolescents with periods of increased energy (mania or hypomania), accompanied by distractibility, pressured speech, irritability, grandiosity, racing thoughts, decreased need for sleep and euphoria/elation.

Findling RL, Steiner H, Weller EB. · Department of Psychiatry, University Hospitals of Cleveland, Cleveland, Ohio 44106-5080, USA. · J Clin Psychiatry. · Pubmed #16124839 No free full text.

Abstract: The comparable efficacy and improved safety of the atypical antipsychotics compared with the traditional antipsychotic agents in the treatment of schizophrenia and other disorders in adults have prompted the use of these agents in children and adolescents. The atypical antipsychotics are increasingly being used in children and adolescents with a variety of different psychiatric diagnoses, including schizophrenia, bipolar disorder, autism/pervasive developmental disorders, conduct disorder, depression, anxiety disorders, tic disorders, delirium, and eating disorders. Unfortunately, clinical use of these agents in pediatric patients has far exceeded the limited evidence from randomized controlled trials. This article reviews the available evidence from the published literature on the use of the atypical antipsychotics in children and adolescents with schizophrenia, bipolar disorder, and maladaptive aggression associated with autism/pervasive developmental disorders and conduct disorder/disruptive behavior disorders.

Youngstrom EA, Findling RL, Youngstrom JK, Calabrese JR. · Department of Psychology, Case Western Reserve University, Cleveland, OH 44106-7123, USA. · J Clin Child Adolesc Psychol. · Pubmed #16026213 No free full text.

Abstract: This article outlines a provisional evidence-based approach to the assessment of pediatric bipolar disorder (PBD). Public attention to PBD and the rate of diagnosis have both increased substantially in the past decade. Accurate diagnosis is crucial to avoid harm due to mislabeling or unnecessary medication exposure. Because there are no proven efficacious or effective treatments for PBD, the role of assessment is heightened to demonstrate efficacy in individual cases as well as to identify cases for participation in clinical trials. This review discusses (a) the state of psychopathology research regarding PBD; (b) the likely base rate of PBD in multiple clinical settings; (c) the diagnostic value of family history; (d) challenges to differential diagnosis, including comorbidity and symptom overlap with other diagnoses, shortcomings in contemporary assessment methods, and the cyclical nature of PBD; (e) practical methods for improving diagnosis, focusing on the most discriminative symptoms, extending the temporal window of assessment to capture mood changes, and using screening tools within an actuarial framework; and (f) monitoring response to treatment using a variety of assessment methods. Twelve recommendations are offered to move toward an evidence-based assessment model for PBD.

Calabrese JR, Rapport DJ, Youngstrom EA, Jackson K, Bilali S, Findling RL. · Case Western Reserve University School of Medicine, University Hospitals of Cleveland, 11400 Euclid Avenue, Suite 200, Cleveland, OH 44106, USA. · Eur Psychiatry. · Pubmed #15797691 No free full text.

Abstract: The rapid cycling variant of bipolar disorder is defined as the occurrence of four periods of either manic or depressive illness within 12 months. Patients suffering from this variant of bipolar disorder have an unmet need for effective treatment. This review examines two major studies in an attempt to update understanding of the current therapies available to treat rapid cycling patients. The first trial compares lamotrigine versus placebo in 182 patients studied for 6 months. The second is a recently completed, 20-month trial comparing divalproate and lithium in 60 patients. Both trials had a double-blind, randomized parallel-group design. The data from the latter study indicate that there are no large differences in efficacy between lithium and divalproate in the long-term treatment of rapid cycling bipolar disorder. In addition, lamotrigine has the potential to complement the spectrum of lithium and divalproate through its greater efficacy for depressive symptoms.

Findling RL. · Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, OH 44106-5080, USA. · Eur Psychiatry. · Pubmed #15797690 No free full text.

Abstract: As the phenomenology of pediatric bipolar disorder has become better delineated, clinicians are now able to more accurately assess and treat young people suffering from this condition. For pediatric patients with bipolar I disorder and symptoms of mania, medication monotherapy has been shown to lead to symptom amelioration. However, this treatment modality oftentimes does not lead to full symptom remission. In an attempt to address this observation, combination treatment strategies have recently been investigated. Recently, a maintenance study has shown that in youths who achieved remission on a combination of lithium and divalproate therapy, either of these agents alone was equally effective as a treatment strategy. In youths identified as being at genetic high risk for bipolarity who also had problematic affective symptomatology, treatment with divalproate was not found to be superior to placebo; however, those with the greatest degree of genetic risk for familial psychopathology remained in the trial longer than those with more modest amounts of familial psychopathology. These data suggest that intervention in youths with only one affected parent may not be a rational prevention strategy for pharmacological intervention in bipolar disorder, and that cohorts more genetically at risk may be a more appropriate group for preventative pharmacotherapy.

Calabrese JR, Vieta E, El-Mallakh R, Findling RL, Youngstrom EA, Elhaj O, Gajwani P, Pies R. · Case University School of Medicine, University Hospitals of Cleveland, 11400 Euclid Avenue, Suite #200, Cleveland, OH 44106, USA. · Biol Psychiatry. · Pubmed #15601606 No free full text.

Abstract: Of the placebo-controlled maintenance studies conducted in bipolar disorder, few have enrolled patients who present depressed. In fact, only lithium and lamotrigine have been studied over the long term with placebo-controlled designs in recently manic and recently depressed bipolar patients. Given the magnitude of the unmet medical need and the data suggesting that symptomatic patients with bipolar disorder spend the majority of their time depressed, this is unfortunate. Our review of the pre-lithium literature and more recent publications suggests that mood state at study entry predicts the polarity of relapse and the response to treatment. Accordingly, a need exists to enroll recently depressed patients in maintenance studies to elucidate the complete spectrum of efficacy of putative mood stabilizers and improve the long-term treatment of bipolar depression. Patients presenting depressed for a maintenance study tend to relapse into depression; those presenting manic, into hypomania/mania/mixed states. This is particularly true during the first several months of the randomized treatment. The polarity of the index episode tends to predict the polarity of relapse into a subsequent episode in a ratio of about 2:1 to 3:1. We conclude that putative mood stabilizers must be tested in recently manic and recently depressed patients to determine their spectrum of prophylactic efficacy.

Findling RL, McNamara NK. · Department of Psychiatry, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, Ohio 44106-5080, USA. · J Clin Psychiatry. · Pubmed #15104524 No free full text.

Abstract: Atypical antipsychotics offer superior safety and similar efficacy compared with conventional agents in adults with psychotic disorders. Consequently, atypical antipsychotics have been increasingly used in children and adolescents. Because most information now available on pediatric use comes from case reports and small open-label studies rather than large controlled trials, treatment in pediatric patients is often guided by experience with adults or based on limited evidence in youths. Although the literature contains reports on the use of each agent in this class in children, risperidone has been the focus of the greatest number of reports. However, the atypical antipsychotics are not interchangeable; each has a unique pharmacologic profile and may differ considerably in terms of adverse effects. Evidence on the use of atypical antipsychotics in children and adolescents is summarized in this review.

Carlson GA, Jensen PS, Findling RL, Meyer RE, Calabrese J, DelBello MP, Emslie G, Flynn L, Goodwin F, Hellander M, Kowatch R, Kusumakar V, Laughren T, Leibenluft E, McCracken J, Nottelmann E, Pine D, Sachs G, Shaffer D, Simar R, Strober M, Weller EB, Wozniak J, Youngstrom EA. · Department of Psychiatry, Stony Brook University-Putnam Hall, Stony Brook, NY 11794-8790, USA. · J Child Adolesc Psychopharmacol. · Pubmed #12804123 No free full text.

Abstract: OBJECTIVE: To achieve consensus among researchers, pharmaceutical industry representatives, federal regulatory agency staff, and family advocates on a template for clinical trials of acute mania/bipolar disorder in children and adolescents. METHOD: The American Academy of Child and Adolescent Psychiatry, in collaboration with Best Practice, convened a group of experts from the key stakeholder communities (including adult psychiatrists with expertise in bipolar disorder) and assigned them to workgroups to examine core methodological issues surrounding the design of clinical trials and, ultimately, to generate a consensus statement encompassing: (1) inclusion/exclusion criteria, (2) investigator training needs and site selection, (3) assessment and outcome measures, (4) protocol design and ethical issues unique to trials involving children/adolescents, and (5) regulatory agency perspectives on these deliberations. RESULTS: Conference participants reached agreement on 18 broad methodological questions. Key points of consensus were to assign priority to placebo-controlled studies of acute manic episodes in children and adolescents aged 10-17 years, who may or may not be hospitalized, and who may or may not suffer from common comorbid psychiatric disorders; to require that specialist diagnostic "gatekeepers" screen youths' eligibility to participate in trials; to monitor interviewer and rater competency over the course of the trial using agreed upon standards; and to develop new tools for assessment, including scales to measure aggression/rage and cognitive function, while using the best available instruments (e.g., Young Mania Rating Scale) in the interim. CONCLUSIONS: Methodologically rigorous, large-scale clinical trials of treatment of acute mania are urgently needed to provide information regarding the safety and efficacy, in youth, of diverse agents with potential mood-stabilizing properties.

Townsend LD, Demeter CA, Youngstrom E, Drotar D, Findling RL. · Case Western Reserve University, Cleveland, 11400 Euclid Avenue, OH 44106, USA. · J Child Adolesc Psychopharmacol. · Pubmed #18315455 No free full text.

Abstract: OBJECTIVE: Family conflict affects the expression of psychopathology in youth. This study investigated whether family conflict moderates response to medication in youth with bipolar disorder. METHODS: Youth ages 5-17 years diagnosed with bipolar I or II disorder were recruited from a trial of combination therapy with divalproex and lithium. Mania and depression were assessed at baseline and after 8 weeks of treatment using the Young Mania Rating Scale (YMRS) and the Children's Depression Rating Scale-Revised (CDRS-R). Parents completed the Family Assessment Device (FAD). Ordinary least-squares regression evaluated whether family conflict contributed to YMRS/CDRS-R outcomes controlling for severity of baseline mood. RESULTS: In 55 youths, the model examining family conflict and CDRS-R outcomes showed that family conflict variables accounted for 10% of the variance in CDRS-R scores after 8 weeks of treatment. The final model was statistically significant. The FAD Problem Solving subscale was the only uniquely significant predictor of CDRS-R scores after 8 weeks of treatment. Family conflict did not predict YMRS outcomes. CONCLUSION: There is a significant relationship between family problem solving and depressive symptoms that persist despite pharmacotherapy. Although depression severity was mild at baseline, it persisted despite pharmacological treatment in youths whose families endorsed higher levels of conflict.

Findling RL, McNamara NK, Stansbrey R, Gracious BL, Whipkey RE, Demeter CA, Reed MD, Youngstrom EA, Calabrese JR. · Department of Psychiatry, Case Western Reserve University, University Hospitals, Cleveland, OH 44106, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #16429084 No free full text.

Abstract: OBJECTIVE: It has been reported that bipolar disorder may become less responsive to previously effective treatment with each symptomatic relapse. The primary goal of this study was to assess the rate of re-stabilization after the resumption of lithium (Li) plus divalproex (DVPX) following relapse on either agent as monotherapy. METHOD: This is a prospective, 8-week, open-label outpatient Li/DVPX combination therapy trial. Patients ages 5 to 17 years with bipolar disorder type I or II, who had achieved symptom remission with Li/DVPX combination therapy and subsequently relapsed during treatment with Li or DVPX monotherapy were enrolled between January 1999 and January 2003. RESULTS: Thirty-eight patients with a mean age of 10.5 years entered the study. Thirty-four (89.5%) patients responded to treatment with Li/DVPX mood stabilizer therapy alone, but four patients required adjunctive antipsychotic treatment to address residual symptomatology. Overall, reinitiation of Li/DVPX combination therapy was well tolerated with no subjects discontinuing because of a medication-related adverse event. CONCLUSIONS: It appears that most youths with bipolar disorder who stabilize on combination Li/DVPX therapy and subsequently relapse during monotherapy can safely and effectively be re-stabilized with the reinitiation of Li/DVPX combination treatment.

Delbello MP, Findling RL, Kushner S, Wang D, Olson WH, Capece JA, Fazzio L, Rosenthal NR. · Center for Bipolar Disorders Research, Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0559, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #15908836 No free full text.

Abstract: OBJECTIVE: To assess the efficacy of topiramate monotherapy for acute mania in children and adolescents with bipolar disorder type I. METHOD: This double-blind, placebo-controlled study was discontinued early when adult mania trials with topiramate failed to show efficacy. Efficacy end points included the Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale for Children, Children's Depression Rating Scale, Children's Global Assessment Scale, and Clinical Global Impressions-Improvement. RESULTS: Fifty-six children and adolescents (6-17 years) with a diagnosis of bipolar disorder type I received topiramate (n=29, 52%) or placebo (n=27, 48%). The only statistically significant differences in efficacy measures between treatment groups were the difference between slopes of the linear mean profiles of the YMRS (p=.003) using a post hoc repeated measures regression and the change in Brief Psychiatric Rating Scale for Children at day 28 (-14.9 versus-5.9, p=.048) using observed data. Adverse events with topiramate included decreased appetite, nausea, diarrhea, and paresthesia. CONCLUSIONS: Topiramate was well tolerated; however, the results are inconclusive because of premature termination resulting in a limited sample size. Adequately powered controlled trials are necessary to determine whether topiramate has efficacy in reducing symptoms of acute mania in children and adolescents.

Findling RL, McNamara NK, Youngstrom EA, Stansbrey R, Gracious BL, Reed MD, Calabrese JR. · Department of Psychiatry, Case Western Reserve University, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #15843762 No free full text.

Abstract: OBJECTIVE: To determine whether divalproex sodium (DVPX) was superior to lithium carbonate (Li+) in the maintenance monotherapy treatment of youths diagnosed with bipolar disorder who had been previously stabilized on combination Li+ and DVPX (Li+/DVPX) pharmacotherapy. METHOD: Youths ages 5-17 years with bipolar I or II disorder were initially treated with Li /DVPX. Patients meeting remission criteria for four consecutive weeks were then randomized in a double-blind fashion to treatment with either Li+ or DVPX for up to 76 weeks. Study participation ended if the subject required additional clinical intervention or if the subject did not adhere to study procedures. RESULTS: Patients were recruited between July 1998 and May 2002. One hundred thirty-nine youths with a mean (SD) age of 10.8 (3.5) years were initially treated with Li+/DVPX for a mean (SD) duration of 10.7 (5.4) weeks. Sixty youths were then randomized to receive monotherapy with Li+ (n = 30) or DVPX (n = 30). The Li+ and DVPX treatment groups did not differ in survival time until emerging symptoms of relapse (p = .55) or survival time until discontinuation for any reason (p = .72). CONCLUSIONS: DVPX was not found to be superior to Li+ as maintenance treatment in youths who stabilized on combination Li+/DVPX pharmacotherapy.

Kahana SY, Youngstrom EA, Findling RL, Calabrese JR. · Case Western Reserve University, Cleveland, Ohio 44106, USA. · J Child Adolesc Psychopharmacol. · Pubmed #14977460 No free full text.

Abstract: The diagnosis of bipolar spectrum disorders (BPSD) is difficult to evaluate in child and adolescent populations. The current study examines whether commonly used behavior checklists- the Child Behavior Checklist, Teacher Report Form, and the Youth Self-Report form-are clinically useful in making a differential diagnosis between BPSD and other disorders. This study is the first to investigate the validity of integrating pairs of informants using these instruments to differentiate individuals with BPSD from those with disruptive behavior disorders, major depressive disorder, and any child or adolescent not meeting criteria for BPSD. Parent report best predicted diagnostic status, yet diagnostic efficiency statistics associated with these checklists were relatively poor. Results indicate that the Child Behavior Checklist has limited utility when attempting to derive clinically meaningful information about the presentation of juvenile BPSD.

Gracious BL, Findling RL, Seman C, Youngstrom EA, Demeter CA, Calabrese JR. · Strong Memorial Hospital, University of Rochester Medical Center, Rochester, NY 14642, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #14726729 No free full text.

Abstract: OBJECTIVE: To examine the effect of combined lithium and divalproex sodium on thyroid-stimulating hormone (TSH) levels in children and adolescents with bipolar disorders and to identify risk factors for lithium-induced hypothyroidism. METHOD: Bipolar youths aged 5 to 17 years participating in an open-label clinical trial received treatment with lithium and divalproex sodium for up to 20 weeks. TSH levels were measured at baseline and at the end of the study. Subjects were divided into two groups for analysis: group 1 had TSH levels of less than 10.0 mU/L at the end of the study and group 2 had TSH levels of 10.0 mU/L or more at end of the study. RESULTS: Twenty of the 82 subjects (24.4%) showed TSH elevations of at least 10 mU/L within an average exposure of less than 3 months. The mean baseline TSH level for group 2 was significantly higher than for group 1 (2.97 [SD = 1.48] versus 2.05 [SD = 0.89], p <.05). Mean lithium levels at the end of the study were 1.00 mEq/L for group 2 compared to 0.76 mEq/L for group 1 (t = -2.41, p =.019). CONCLUSIONS: Lithium is associated with significant rates of thyrotropin elevation in bipolar youths. Factors associated with elevation in TSH in lithium-treated subjects include a higher baseline TSH level and a higher lithium level. Close monitoring of thyroid function in children and adolescents taking lithium is recommended.