Bipolar Disorder: Wagner KD

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.

Wagner KD. · No affiliation provided · J Clin Psychiatry. · Pubmed #19552868 No free full text.

This publication has no abstract.

Wagner KD. · · J Clin Psychiatry. · Pubmed #19203477 No free full text.

This publication has no abstract.

Wagner KD. · Departmetn of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston, TX 77555-0188, USA. · J Clin Psychiatry. · Pubmed #15554794 No free full text.

Abstract: Bipolar disorder is a serious illness in children that adversely affects social, academic, emotional, and family functioning. Its prevalence in adolescents is estimated to be as high as 1%. The diagnosis of bipolar disorder in young children is often a challenge, largely because the symptoms may differ from those exhibited in late adolescence and adulthood. The occurrence of comorbid disorders such as attention-deficit/hyperactivity disorder also may complicate the diagnosis. Despite the significant severity and chronicity of this disorder in youths, very few controlled data are available to guide treatment decisions in children and adolescents. The treatment literature consists largely of open studies, case series, and case reports. Therefore, a pressing need exists for controlled trials to determine whether medications commonly used to treat the disorder in children are significantly superior to placebo, as well as to determine whether initial monotherapy or combination treatment is warranted. This article will review the epidemiology, diagnosis, course of illness, and treatment of bipolar disorder in children and adolescents.

Wolf DV, Wagner KD. · Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston, Texas 77555-0188, USA. · CNS Spectr. · Pubmed #14978470 No free full text.

Abstract: There is increased recognition that bipolar disorder has an early age of onset. The prevalence of bipolar disorder in prepubertal children has not been determined, however the prevalence in adolescence is approximately 1%. Bipolar disorder in children poses a diagnostic challenge since the symptoms may differ from those in late adolescence and adulthood. Comorbid disorders, such as attention-deficit/hyperactivity disorder, further complicate both the diagnosis and course of the disorder. There is increasing evidence of the chronicity and severity of this disorder in youths. Bipolar disorder significantly disrupts a child's psychosocial development including impairments in academic functioning, family functioning, and relationship with peers. Although this disorder has significant morbidity in children and adolescents, there is a paucity of controlled studies to assess the efficacy and safety of mood stabilizers in the treatment of this disorder in youths. The treatment literature consists largely of case studies, retrospective chart reviews, and open-label studies. There is a compelling need for double-blind, placebo-controlled trials to determine whether commonly used medications to treat this disorder are significantly superior to placebo. Since many children in clinical practice require more than one psychotropic medication to adequately manage this disorder, studies of combination treatments are warranted. This review will provide an overview of the literature of bipolar disorder in children and adolescents, including discussion of the prevalence, diagnosis, epidemiology, course of the illness, and treatment issues.

Redden L, DelBello M, Wagner KD, Wilens TE, Malhotra S, Wozniak P, Vigna NV, Greco N, Kovacs X, Abi-Saab W, Saltarelli M, Anonymous00046. · Abbott, Abbott Park, Illinois 60064, USA. · J Child Adolesc Psychopharmacol. · Pubmed #19232026 No free full text.

Abstract: OBJECTIVE: The objective of this open-label study was to assess the safety of divalproex sodium extended-release in the treatment of children and adolescents with acute mania associated with bipolar I disorder. METHODS: This was a 6-month, Phase 3, open-label study in healthy subjects aged 9-17 years with a current Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition, Text Revision (DSM-IV-TR) diagnosis of bipolar I disorder manic or mixed episode. Divalproex sodium extended-release (DVPX-ER) was initiated at 15 mg/kg per day on day 1 (not to exceed 750 mg/day) with increases allowed to a maximum of 35 mg/kg per day. Study visits were conducted on day 1 and at months 1, 2, 3, and 6. Assessments included standard safety evaluations and appropriate rating scales for clinical effect. RESULTS: A total of 226 subjects were enrolled; 109 subjects completed the study. The most common adverse events were weight gain (16%), nausea (9%), and increased appetite (8%). Nonsymptomatic elevations of mean ammonia levels in plasma were observed. The mean Young Mania Rating Scale (YMRS) decreased 12.4 from baseline to final visit; small improvements were seen in behavior and caregiver stress ratings. CONCLUSIONS: DVPX-ER was generally well tolerated in children and adolescents with acute mania, with a side-effect profile similar to that observed in adults.

Wagner KD, Weller EB, Carlson GA, Sachs G, Biederman J, Frazier JA, Wozniak P, Tracy K, Weller RA, Bowden C. · University of Texas Medical Branch, Galveston, TX 77555-0188, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #12364844 No free full text.

Abstract: OBJECTIVE: This study evaluated the safety and effectiveness of divalproex sodium (Depakote ) in the treatment of youths with bipolar disorder. METHOD: Forty bipolar disorder patients aged 7 to 19 years, with a manic, hypomanic, or mixed episode, enrolled in an open-label study of divalproex (2-8 weeks), followed by a double-blind, placebo-controlled period (8 weeks). RESULTS: Twenty-two subjects (61%) showed > or =50% improvement in Mania Rating Scale (MRS) scores during the open-label period. Significant ( <.001) improvements from baseline were seen for mean scores of all efficacy measures, including the MRS, Manic Syndrome Scale, Behavior and Ideation Scale, Brief Psychiatric Rating Scale, Clinical Global Impressions Severity scale, and Hamilton Rating Scale for Depression. Of the 23 subjects who discontinued the study during the open-label period, 6 (15%) discontinued for ineffectiveness, 6 (15%) for intolerance, 6 (15%) for noncompliance, and 6 (15%) for other reasons. Adverse events were generally mild or moderate in severity, with the most common being headache, nausea, vomiting, diarrhea, and somnolence. Laboratory data results were unremarkable. Too few subjects participated in the double-blind period for statistical analysis. CONCLUSION: This study provides preliminary support for the safety and effectiveness of divalproex in the treatment of bipolar disorder in youths.

Wagner KD, Redden L, Kowatch RA, Wilens TE, Segal S, Chang K, Wozniak P, Vigna NV, Abi-Saab W, Saltarelli M. · University of Texas Medical Branch, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #19325497 No free full text.

Abstract: OBJECTIVE: To compare the efficacy and safety of divalproex extended-release (ER) to placebo in a 28-day double-blind study of bipolar disorder in children and adolescents and evaluate the safety of divalproex ER in a 6-month open-label extension study. METHOD: In the double-blind study, 150 patients (manic or mixed episode, aged 10-17 years) with baseline Young Mania Rating Scale (YMRS) score of 20 or higher were randomized to once-daily placebo or divalproex ER, which was titrated to clinical response or serum valproate concentration of 80 to 125 microg/mL. Sixty-six patients enrolled in the extension study. RESULTS: In the double-blind study, a treatment effect was not observed with divalproex ER based on change in mean YMRS score (divalproex ER -8.8 [n = 74]; placebo -7.9 [n = 70]) or secondary measures. Divalproex was similar to placebo based on incidence of adverse events. Four subjects treated with divalproex ER and three treated with placebo discontinued because of adverse events. Mean ammonia levels increased in the divalproex ER group, but only one patient was symptomatic. In the long-term study, YMRS scores decreased modestly (2.2 points from baseline). The most common adverse events were headache and vomiting. CONCLUSIONS: The results of the study do not provide support for the use of divalproex ER in the treatment of youths with bipolar I disorder, mixed or manic state. Further controlled trials are required to confirm or refute the findings from this study.

Carlson GA, Findling RL, Post RM, Birmaher B, Blumberg HP, Correll C, DelBello MP, Fristad M, Frazier J, Hammen C, Hinshaw SP, Kowatch R, Leibenluft E, Meyer SE, Pavuluri MN, Wagner KD, Tohen M. · Department of Child and Adolescent Psychiatry, Stony Brook University School of Medicine, Stony Brook, New York, USA. · J Child Adolesc Psychopharmacol. · Pubmed #19232018 No free full text.

Abstract: OBJECTIVE: The 2006 Research Forum addressed the goal of formulating a research agenda for early-onset bipolar disorder (EOBP) and improving outcome by understanding the risk and protective factors that contribute to its severity and chronicity. METHOD: Five work groups outlined barriers and research gaps in EOBP genetics, neuroimaging, prodromes, psychosocial factors, and pharmacotherapy. RESULTS: There was agreement that the lack of consensus on the definition and diagnosis of EOBP is the primary barrier to advancing research in BP in children and adolescents. Related issues included: the difficulties in managing co-morbidity both statistically and clinically; acquiring adequate sample sizes to study the genetics, biology, and treatment; understanding the EOBP's developmental aspects; and identifying environmental mediators and moderators of risk and protection. Similarly, both psychosocial and medication treatment strategies for children with BP are hamstrung by diagnostic issues. To advance the research in EOBP, both training and funding mechanisms need to be developed with these issues in mind. CONCLUSIONS: EOBP constitutes a significant public health concern. Barriers are significant but identifiable and thus are not insurmountable. To advance the understanding of EOBP, the field must be committed to resolving diagnostic and assessment issues. Once achieved, with adequate personnel and funding resources, research into the field of EOBP will doubtless be advanced at a rapid pace.

Hirschfeld RM, Calabrese JR, Frye MA, Lavori PW, Sachs G, Thase ME, Wagner KD. · Psychiatry and Behavioral Sciences, The University of Texas Medical Branch, Galveston, TX. · Psychopharmacol Bull. · Pubmed #18007564 No free full text.

Abstract: Objective: This manuscript presents working definitions for key clinical course indicators for bipolar disorder, including response, remission, relapse, recurrence, and roughening. Method: A work group of experts in bipolar disorder reviewed prior efforts to define clinical course indicators for unipolar depression and for schizophrenia. Using these efforts as templates, the work group developed consensus operational definitions. The rationale for each of the definitions was a point of time when a treatment decision needed to be made. Results: The group defined response as a 50% reduction in a score from a standard rating scale of symptomatology from an appropriate baseline, regardless of index episode type (manic, depressed, or mixed). In addition, the other pole cannot be significantly worsened during response. Remission was defined as absence or minimal symptoms of both mania and depression for at least 1 week. Sustained remission requires at least eight consecutive weeks of remission, and perhaps as many as 12 weeks. A relapse/recurrence was defined as a return to the full syndrome criteria of an episode of mania, mixed episode, or depression following a remission of any duration. Roughening was defined as a return of symptoms at a subsyndromal level, perhaps representing a prodrome of an impending episode. Conclusions: The work group recommends that all reports of clinical trials in bipolar disorder include results using these definitions. This will introduce standards for such reports. Hopefully, the definitions will be revised and improved over time.

Wagner KD, Hirschfeld RM, Emslie GJ, Findling RL, Gracious BL, Reed ML. · Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston 77555-0188, USA. · J Clin Psychiatry. · Pubmed #16841633 No free full text.

Abstract: OBJECTIVE: The study was designed to determine the validity of the Mood Disorder Questionnaire-Adolescent Version (MDQ-A) as a screening instrument for bipolar disorders (I, II, not otherwise specified, and cyclothymia) in an adolescent outpatient psychiatric population. METHOD: 104 adolescents and their parents completed the MDQ-A. Three versions of the MDQ-A were compared: (1) self report of symptoms by adolescent, (2) attributional report-how the adolescent believed teachers or friends would report his/her symptoms, and (3) parent report of adolescent's symptoms. DSM-IV diagnosis was made based upon the clinician-administered Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), a semistructured diagnostic interview. MDQ-A items were summed, yielding a score for each adolescent ranging from 0 to 13 on each of the 3 MDQ-A versions. Each possible scoring threshold, in combination with co-occurrence of symptoms and behaviors and with moderate to serious problems caused by symptoms, was crossed with the results of the K-SADS-PL diagnostic interview to assess sensitivity and specificity. The study was conducted from April 2002 to September 2003. RESULTS: A score of 5 or more items on the parent version yielded a sensitivity of 0.72 and specificity of 0.81, which were superior to self and attributional versions. CONCLUSIONS: The MDQ-A completed by parents about their adolescents' symptoms may be a useful screening instrument for bipolar disorders in an adolescent psychiatric outpatient population.

Wagner KD, Kowatch RA, Emslie GJ, Findling RL, Wilens TE, McCague K, D'Souza J, Wamil A, Lehman RB, Berv D, Linden D. · Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77755-0188, USA. · Am J Psychiatry. · Pubmed #16816222 links to  free full text

Abstract: OBJECTIVE: This multicenter trial examined the efficacy and safety of oxcarbazepine in the treatment of bipolar disorder in children and adolescents. METHOD: A total of 116 outpatients 7 to 18 years of age with bipolar I disorder, manic or mixed, were recruited at 20 centers in the United States and randomly assigned to receive 7 weeks of double-blinded, flexibly dosed treatment with oxcarbazepine (maximum dose 900-2400 mg/day) or placebo. The primary efficacy measure was the mean change from baseline to endpoint in the Young Mania Rating Scale (YMRS), using the last-observation-carried-forward method. RESULTS: Oxcarbazepine (mean dose=1515 mg/day) did not significantly improve YMRS scores at endpoint compared with placebo [adjusted mean change: oxcarbazepine, -10.90 (N=55); placebo, -9.79 (N=55)]. Dizziness, nausea, somnolence, diplopia, fatigue, and rash were each reported in at least 5% of the patients in the oxcarbazepine group with an incidence at least twice that of the placebo group. The majority of adverse events were mild to moderate and occurred during the titration period. Eleven patients (19%) in the oxcarbazepine group discontinued the study because of adverse events, compared with two (4%) in the placebo group. CONCLUSIONS: Oxcarbazepine is not significantly superior to placebo in the treatment of bipolar disorder in youths. While the overall adverse event profile was similar to that reported for patients with epilepsy, the incidence of psychiatric adverse events for both the oxcarbazepine and placebo groups was higher than that reported for the epilepsy population.

Frye MA, Calabrese JR, Reed ML, Wagner KD, Lewis L, McNulty J, Hirschfeld RM. · Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, 300 UCLA Medical Plaza, Suite 1544, Los Angeles, California 90095, USA. · Psychiatr Serv. · Pubmed #16339614 links to  free full text

Abstract: OBJECTIVE: This study examined patterns of diagnosis, consultation, and treatment of persons who screened positive for bipolar disorder. METHODS: An impact survey was mailed to a representative subset of 3,059 individuals from a large U.S.-population-based study that utilized the Mood Disorder Questionnaire (MDQ). RESULTS: Respondents who screened positive on the MDQ (reported the presence of seven of 13 symptoms of bipolar disorder, the co-occurrence of at least two symptoms, and moderate or severe symptom-related impairment) (N=1,167) had consulted a health care provider more often in the previous year than those who screened negative (reported six or fewer symptoms regardless of symptom co-occurrence or impairment) (N=1,283). Psychiatrists and primary care physicians failed to detect or misdiagnosed bipolar disorder among 53 percent and 78 percent of patients, respectively, who screened positive for bipolar disorder. The most commonly used psychotropic medications during the previous 12 months among those who screened positive were antidepressants alone (32 percent), followed by lithium and anticonvulsant mood stabilizers (20 percent), antidepressants in combination with other psychotropics (19 percent), hypnotics (19 percent), and antipsychotics (9 percent). In the preceding 12 months, respondents who screened positive on the MDQ had greater use of psychiatric hospitals, emergency departments, and urgent care centers and also had more outpatient visits to primary care physicians, psychiatrists, and alcohol treatment centers than those who screened negative. CONCLUSIONS: The results of this study suggest that bipolar disorder is an underdiagnosed and often inappropriately treated illness associated with significant use of health care resources.

Calabrese JR, Hirschfeld RM, Reed M, Davies MA, Frye MA, Keck PE, Lewis L, McElroy SL, McNulty JP, Wagner KD. · Department of Psychiatry, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, Ohio 44106, USA. · J Clin Psychiatry. · Pubmed #12716245 No free full text.

Abstract: BACKGROUND: Bipolar disorder is a chronic psychiatric illness characterized by depression and at least 1 manic or hypomanic episode during the lifetime of the illness. Bipolar symptoms have been associated with significant functional impairment. We conducted a study to determine the psychosocial impact of bipolar disorder in a U.S. community sample. METHOD: 3059 subjects were selected from a large epidemiologic study of bipolar prevalence that used the Mood Disorder Questionnaire (MDQ) to screen for bipolar I and II disorder. Subjects were surveyed from April 24, 2001, to August 6, 2001, using the Sheehan Disability Scale and the Social Adjustment Scale-Self Report. Comorbid disease data were also collected. RESULTS: Of the 3059 subjects surveyed, 2450 (80%) returned completed surveys: 1167 (48%) subjects screened positive for bipolar disorder based on MDQ scores; 1283 (52%) screened negative. MDQ-positive subjects reported significantly (p <.0001) more difficulties with work-related performance, social/leisure activities, and social/family interactions compared with MDQ-negative subjects. Younger subjects, aged 18 to 34 years, reported significantly (p =.003) more symptom days than did older MDQ-positive subjects. MDQ-positive women reported more disruption in social and family life, while MDQ-positive men reported being jailed, arrested, and convicted for crimes. Anxiety (30% vs. 6%), panic attacks (18% vs. 4%), migraine (24% vs. 11%), asthma (17% vs. 10%), and allergies (42% vs. 29%) were significantly (p <.05) more common in MDQ-positive versus MDQ-negative subjects. CONCLUSION: Bipolar disorder, as identified in a community sample using the Mood Disorder Questionnaire, was significantly associated with negative impact on the performance of work-related, leisure, and interpersonal activities.

Hirschfeld RM, Calabrese JR, Weissman MM, Reed M, Davies MA, Frye MA, Keck PE, Lewis L, McElroy SL, McNulty JP, Wagner KD. · Department of Psychiatry & Behavioral Sciences, University of Texas Medical Branch, Galveston, 77555-188, USA. · J Clin Psychiatry. · Pubmed #12590624 No free full text.

Abstract: BACKGROUND: Our goal was to estimate the rate of positive screens for bipolar I and bipolar II disorders in the general population of the United States. METHOD: The Mood Disorder Questionnaire (MDQ), a validated screening instrument for bipolar I and II disorders, was sent to a sample of 127,800 people selected to represent the U.S. adult population by demographic variables. 85,358 subjects (66.8% response rate) that were 18 years of age or above returned the survey and had usable data. Of the nonrespondents, 3404 subjects matched demographically to the 2000 U.S. Census data completed a telephone interview to estimate nonresponse bias. RESULTS: The overall positive screen rate for bipolar I and II disorders, weighted to match the 2000 U.S. Census demographics, was 3.4%. When adjusted for the nonresponse bias, the rate rose to 3.7%. Only 19.8% of the individuals with positive screens for bipolar I or II disorders reported that they had previously received a diagnosis of bipolar disorder from a physician, whereas 31.2% reported receiving a diagnosis of unipolar depression. An additional 49.0% reported receiving no diagnosis of either bipolar disorder or unipolar depression. Positive screens were more frequent in young adults and low income households. The rates of migraine, allergies, asthma, and alcohol and drug abuse were substantially higher among those with positive screens. CONCLUSION: The positive MDQ screen rate of 3.7% suggests that nearly 4% of American adults may suffer from bipolar I and II disorders. Young adults and individuals with lower income are at greater risk for this largely underdiagnosed disorder.

Hirschfeld RM, Holzer C, Calabrese JR, Weissman M, Reed M, Davies M, Frye MA, Keck P, McElroy S, Lewis L, Tierce J, Wagner KD, Hazard E. · Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, 1.302 Rebecca Sealy, 301 University Blvd., Galveston, TX 77555-0188, USA. · Am J Psychiatry. · Pubmed #12505821 links to  free full text

Abstract: OBJECTIVE: This study tested the validity in the adult general population of the Mood Disorder Questionnaire, a screening instrument for bipolar I and II disorders. The Mood Disorder Questionnaire has been validated in a psychiatric outpatient study group. METHOD: A total of 711 subjects (stratified by Mood Disorder Questionnaire score) were randomly selected from a group of 85,358 adult respondents in a nationwide epidemiological general population sample that was balanced for key demographic variables. Of these, 695 subjects received a telephone interview involving an abbreviated version of the Structured Clinical Interview for DSM-IV. RESULTS: A sensitivity of 0.281 and a specificity of 0.972 were obtained for the Mood Disorder Questionnaire. CONCLUSIONS: The Mood Disorder Questionnaire is a useful screening instrument for bipolar I and II disorders in the community. The operating characteristics of the Mood Disorder Questionnaire in the general population differ substantially from its characteristics in outpatient psychiatric settings.