Integrating Pharmacotherapy and Psychotherapy for Paediatric Bipolar Disorder: Translating Science to Service

Objective: For comprehensive management of paediatric bipolar disorder (PBD), it is imperative to combine psychopharmacotherapy with specific psychotherapy. This article proposes a model that incorporates (1) an overview of psychopathology, (2) a review of outcomes in psychopharmacotherapy trials, and (3) a summary of evidence-based forms of psychotherapy to complement pharmacotherapy. Results: The psychopathology of PBD is unique compared to that of adult bipolar disorder with prominent irritability, rapid cycling, high rates of co-morbid attention deficit hyperactivity disorder, mixed episodes and chronicity. Combination therapy with a second generation antipsychotic and a mood stabilizer is proving to be more effective than monotherapy with a mood stabilizer. Empirical findings for the support of family-focused, cognitive behavioral therapies with individual family or multifamily psychoeducation groups suggest that these psychosocial treatments are valuable complementary tools for clinicians who treat youths diagnosed with PBD. Conclusion: As pharmacotherapy and psychotherapy are most beneficial when applied together, the clinician’s understanding of the science behind these forms of treatment is likely to be of great value in effectively providing services to youths diagnosed with PBD

Review of risperidone for the treatment of pediatric and adolescent bipolar disorder and schizophrenia

Risperidone is a commonly used medication for the treatment of bipolar disorder and schizophrenia in children and adolescents. It has been studied as a monotherapy treatment in early onset schizophrenia and as both monotherapy and combination therapy for pediatric bipolar disorder. Studies to date indicate that risperidone is an effective treatment for positive and negative symptoms of schizophrenia and mania symptoms of bipolar disorder. In young patient populations, side effects such as weight gain, extrapyramidal side effects, and prolactin elevation require consideration when evaluating the risk benefit ratio for individual patients. Here we review published studies of risperidone for the treatment of bipolar disorder and schizophrenia in children and adolescents to provide practitioners with an overview of published data on the efficacy and safety of risperidone in these patient populations

AACAP 2006 Research Forum--Advancing research in early-onset bipolar disorder: barriers and suggestions

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\u27s 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

Meta-Analyses of Developing Brain Function in High-Risk and Emerged Bipolar Disorder

Objectives: Identifying early markers of brain function among those at high risk for pediatric bipolar disorder (PBD) could serve as a screening measure when children and adolescents present with sub-syndromal clinical symptoms prior to the conversion to bipolar disorder. Studies on the offspring of patients with bipolar disorder who are genetically at high risk (HR) have each been limited in establishing a biomarker, while an analytic review in summarizing the findings offers an improvised opportunity towards that goal. Methods: An activation likelihood estimation meta-analysis of mixed cognitive and emotional activities using the GingerALE software from the BrainMap Project was completed. The meta-analysis of all fMRI studies contained a total of 29 reports and included PBD, HR and typically developing (TD) groups.Results: The HR group showed significantly greater activation relative to the TD group in the right DLPFC-insular-parietal-cerebellar regions. Similarly, the HR group exhibited greater activity in the right DLPFC and insula as well as the left cerebellum compared to patients with PBD. Patients with PBD, relative to TD, showed greater activation in regions of the right amygdala, parahippocampal gyrus, medial PFC, left ventral striatum, and cerebellum and lower activation in the right VLPFC and the DLPFC.Conclusions: The HR population showed increased activity, presumably indicating greater compensatory deployment, in relation to both the TD and the PBD, in the key cognition and emotion processing regions, such as the DLPFC, insula and parietal cortex. In contrast, patients with PBD, relative to HR and TD, showed decreased activity, which could indicate a decreased effort in multiple PFC regions in addition to widespread subcortical abnormalities, which are suggestive of a more entrenched disease process

Fronto-limbic Dysfunction in Mania Pre-Treatment and Persistent Amygdala Over-activity Post-Treatment in Pediatric Bipolar Disorder

Rationale. Neural deficits at the interface of affect and cognition may improve with pharmacotherapy in pediatric bipolar disorder (PBD). Objectives. We examined lamotrigine treatment impact on the neural interface of working memory and affect in PBD. Methods. Un-medicated, acutely-ill, patients with mania and hypomania (n=17) and healthy controls (HC; n=13) (mean age = 13.36 ± 2.55) performed an affective 2-back fMRI task with blocks of angry vs neutral faces (i.e., angry face condition) or happy vs neutral faces (i.e., happy face condition) before treatment and at follow-up, after 8-week treatment with second generation antipsychotics (SGAs) followed by 6 weeks of lamotrigine monotherapy. Results. At baseline, for the angry face condition, PBD, relative to HC, showed reduced activation in left ventrolateral prefrontal cortex (VLPFC) and right caudate; for the happy face condition, they showed increased activation in bilateral PFC, and right amygdala and middle temporal gyrus. Post treatment, PBD showed greater activation in right amygdala relative to HC, for both conditions. Patients, relative to HC, exhibited greater changes over time in right VLPFC and amygdala, left subgenual anterior cingulated cortex (ACC) and left caudate for the angry face condition, and in right middle temporal gyrus for the happy face condition. Conclusions. Pharmacotherapy resulted in symptom improvement and normalization of higher cortical emotional and cognitive regions in patients relative to HC, suggesting that VLPFC dysfunction may be state-specific in PBD. Amygdala was overactive in PBD, relative to HC, regardless of reduction in manic symptoms, and may be a trait marker of PBD