Bipolar Disorder: McClellan J

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.

Findling RL, Frazier JA, Kafantaris V, Kowatch R, McClellan J, Pavuluri M, Sikich L, Hlastala S, Hooper SR, Demeter CA, Bedoya D, Brownstein B, Taylor-Zapata P. · Department of Psychiatry, University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, OH, USA. · Child Adolesc Psychiatry Ment Health. · Pubmed #18700004 links to  free full text

Abstract: ABSTRACT: BACKGROUND: Lithium is a benchmark treatment for bipolar illness in adults. However, there has been relatively little methodologically stringent research regarding the use of lithium in youth suffering from bipolarity. METHODS: Under the auspices of the Best Pharmaceuticals for Children Act (BPCA), a Written Request (WR) pertaining to the study of lithium in pediatric mania was issued by the United States Food and Drug Administration (FDA) to the National Institute of Child Health and Human Development (NICHD) in 2004. Accordingly, the NICHD issued a Request for Proposals (RFP) soliciting submissions to pursue this research. Subsequently, the NICHD awarded a contract to a group of investigators in order to conduct these studies. RESULTS: The Collaborative Lithium Trials (CoLT) investigators, the BPCA-Coordinating Center, and the NICHD developed protocols to provide data that will: (1) establish evidence-based dosing strategies for lithium; (2) characterize the pharmacokinetics and biodisposition of lithium; (3) examine the acute efficacy of lithium in pediatric bipolarity; (4) investigate the long-term effectiveness of lithium treatment; and (5) characterize the short- and long-term safety of lithium. By undertaking two multi-phase trials rather than multiple single-phase studies (as was described in the WR), the feasibility of the research to be undertaken was enhanced while ensuring all the data outlined in the WR would be obtained. The first study consists of: (1) an 8-week open-label, randomized, escalating dose Pharmacokinetic Phase; (2) a 16-week Long-Term Effectiveness Phase; (3) a 28-week double-blind Discontinuation Phase; and (4) an 8-week open-label Restabilization Phase. The second study consists of: (1) an 8-week, double-blind, parallel-group, placebo-controlled Efficacy Phase; (2) an open-label Long-Term Effectiveness lasting either 16 or 24 weeks (depending upon blinded treatment assignment during the Efficacy Phase); (3) a 28-week double-blind Discontinuation Phase; and (4) an 8-week open-label Restabilization Phase. In December of 2006, enrollment into the first of these studies began across seven sites. CONCLUSION: These innovative studies will not only provide data to inform the labeling of lithium in children and adolescents with bipolar disorder, but will also enhance clinical decision-making regarding the use of lithium treatment in pediatric bipolar illness. TRIAL REGISTRATION: NCT00442039.

Hlastala SA, McClellan J. · Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA. · J Child Adolesc Psychopharmacol. · Pubmed #16092913 No free full text.

Abstract: OBJECTIVE: This study aimed to better characterize the phenomenology and diagnostic stability of youths that report atypical psychotic symptoms. METHOD: In a 2-year longitudinal follow-up study, youths reporting atypical psychotic symptoms (n = 20) were compared with youths with schizophrenia (n = 27) and youths with bipolar disorder with psychotic features (n = 22) on psychotic, dissociative, and general symptomatology, comorbid diagnoses, previous abuse, and overall functioning. Diagnoses were obtained using structured diagnostic interviews (i.e., the Structured Clinical Interview for DSM-IV and the Diagnostic Interview for Children and Adolescents). RESULTS: None of the subjects reporting atypical psychotic symptoms went on to develop a classic psychotic illness by the year 2 follow-up. These subjects had significantly higher rates of abuse and dissociative symptoms, and were significantly more likely to receive a diagnosis of posttraumatic stress disorder (PTSD) or a depressive disorder than youths with schizophrenia or bipolar disorder. CONCLUSION: Our findings suggest that youths with atypical, fleeting, or situationally specific hallucinations are more likely to have a mood or anxiety disorder (such as PTSD) than a current or prodromal psychotic illness.

McClellan J. · Department of Psychiatry, University of Washington, Seattle 98195, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #15725967 No free full text.

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McClellan J, Prezbindowski A, Breiger D, McCurry C. · Department of Psychiatry CH-13, University of Washington, Seattle, WA 98195, USA. · Schizophr Res. · Pubmed #15037336 No free full text.

Abstract: This paper examines whether neuropsychological profiles of youth with early onset psychotic disorders predicted diagnostic or clinical status. Youth with schizophrenia (n=27), bipolar disorder (n=22), and psychosis NOS (n=20) were included. Subjects received an extensive neuropsychological evaluation, including measures of general cognition, attention, memory, and executive functioning. Medication status was not controlled. No statistically significant neurocognitive differences across diagnostic groups were found. Compared to standardized norms, youth with schizophrenia demonstrated deficits in general cognition, verbal learning, recall, sustained effort, and social knowledge. Subjects with bipolar disorder and psychosis NOS exhibited deficits on measures of verbal learning, recall, and sustained effort similar to those of youth with schizophrenia. Neurocognitive deficits in memory and attention appeared to be common among youth with psychotic illnesses, regardless of diagnosis. Those with schizophrenia may have greater global cognitive deficits and problems with social knowledge. Across diagnoses, subjects demonstrated relative strengths on tests that provided them with immediate feedback, and performed most poorly on tests requiring delayed recall.

McClellan J, Breiger D, McCurry C, Hlastala SA. · Department of Psychiatry, University of Washington, Seattle 98195, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #12921474 No free full text.

Abstract: OBJECTIVE: To examine the premorbid characteristics of youths with early-onset psychotic disorders. METHOD: Subjects with early-onset psychotic disorders received an extensive diagnostic evaluation upon entry into the study, including a historic review of premorbid functioning using the Premorbid Adjustment Scale. RESULTS: Youths with schizophrenia (n = 27), bipolar disorder (n = 22), and psychosis not otherwise specified (NOS) (n = 20) were included. High rates of premorbid behavioral problems and academic difficulties were noted across all subjects. Youths with schizophrenia had higher rates of premorbid social withdrawal and global impairment. They also tended to have fewer friends. The psychosis NOS group had significantly higher rates of abuse histories and posttraumatic stress disorder. CONCLUSIONS: Premorbid abnormalities are common features of early-onset psychotic disorders. The social withdrawal and peer problems specific to youths with schizophrenia likely represent early manifestations of negative symptoms. The abuse histories in the psychosis NOS group may explain the atypical nature of their reported psychotic symptoms, which in many cases are likely posttraumatic phenomena.

McClellan J, McCurry C, Speltz ML, Jones K. · Department of Psychiatry, University of Washington, Seattle, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #12108803 No free full text.

Abstract: OBJECTIVE: To examine the factor structure of symptom ratings in early-onset psychotic illnesses. METHOD: Subjects were drawn from a 2-year prospective study of early onset psychotic disorders. Principal components analysis with orthogonal (varimax) rotation was used to create factors from baseline ratings on the Schedule for Positive Symptoms, the Schedule for Negative Symptoms, and the Brief Psychiatric Rating Scale for Children. RESULTS: Youths with schizophrenia (n = 27), bipolar disorder (n = 22), and psychosis not otherwise specified (n = 20) were included. Four symptom factors were identified: negative symptoms, positive symptoms, behavioral problems, and dysphoria. Negative symptoms were predictive of the diagnosis of schizophrenia and treatment with antipsychotic medications. Neither behavior problems nor dysphoria were predictive of diagnosis. In subjects who completed follow-up assessments at year 1 (n = 49) and year 2 (n = 39), negative symptoms and behavioral problems predicted poorer functioning. CONCLUSIONS: The four factors are clinically relevant, with both treatment planning and prognostic implications. Negative symptoms best differentiated schizophrenia from the other disorders. Behavior problems and dysphoria were nonspecific problems that occurred in all three disorders, which likely leads to misdiagnosis in community settings.

McClellan J, McCurry C, Snell J, DuBose A. · Department of Psychiatry, University of Washington, Seattle 98195, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #10560224 No free full text.

Abstract: OBJECTIVE: To examine the course and outcome of early-onset psychotic disorders. METHOD: These are data from a longitudinal, prospective study of youths with psychotic disorders. Standardized diagnostic and symptom rating measures were used. RESULTS: Fifty-five subjects with the following disorders have been recruited: schizophrenia (n = 18), bipolar disorder (n = 15), psychosis not otherwise specified (n = 15), schizoaffective disorder (n = 6), and organic psychosis (n = 1). Follow-up assessments were obtained on 42 subjects at year 1 and 31 subjects at year 2. Youths with schizophrenia had more chronic global dysfunction, whereas subjects with bipolar disorder overall had better functioning, with a cyclical course of illness. However, according to results of a regression model, premorbid functioning and ratings of negative symptoms, but not diagnosis, significantly predicted the highest level of functioning over years 1 and 2. CONCLUSIONS: Course and level of functioning differentiated bipolar disorder from schizophrenia. However, premorbid functioning and ratings of negative symptoms were the best predictors of functioning over the follow-up period. These findings are consistent with the adult literature, and they further support that psychotic illnesses in young people are continuous with the adult-onset forms.

McClellan J, McCurry C. · University of Washington's Department of Psychiatry, Seattle 98195, USA. · Eur Child Adolesc Psychiatry. · Pubmed #10546979 No free full text.

Abstract: OBJECTIVES: To examine the clinical features and diagnostic stability of early-onset psychotic disorders. METHODS: These data are from a two-year longitudinal prospective study of youth with psychotic disorders. Standardized diagnostic assessments are administered at baseline and at one and two-year's follow-up. RESULTS: Fifty-one subjects have been recruited to date; 18 with schizophrenia, 14 with bipolar disorder, 7 with schizoaffective disorder, 1 with an organic psychosis, and 11 subjects whose symptoms where either questionable and/or did not meet diagnostic criteria for another disorder (classified as psychosis nos). Thirty-nine subjects were reassessed at year one, twenty-four at year two. Three subjects have been lost to follow-up. The study diagnosis was the same as the first onset diagnosis (prior to entering the study) in 50% of subjects. Over the two-year period of the study, the diagnosis remained unchanged in over 90% of subjects. Subjects with schizophrenia had higher ratings of premorbid impairment, including social withdrawal and dysfunctional peer relationships, than those with bipolar disorder. At the one-year follow-up, subjects with schizophrenia and schizoaffective disorder had significantly higher rates of delusions, bizarre behavior, and negative symptoms than those with bipolar disorder. Subjects with bipolar disorder tended to have cyclical courses, whereas those with schizophrenia and schizoaffective disorder were often chronically impaired. Subjects with psychosis nos had higher rates of dissociative symptoms and histories of child maltreatment. CONCLUSIONS: Early-onset psychotic disorders can be reliably diagnosed using standardized assessments and are stable over a two-year period. Compared to bipolar disorder, schizophrenia is associated with a poorer premorbid history, and persistent positive and negative symptoms.