Maintenance treatment of adolescent bipolar disorder: open study of the effectiveness and tolerability of quetiapine

<p>Abstract</p> <p>Background</p> <p>The purpose of the study was to determine the effectiveness and tolerability of quetiapine as a maintenance treatment preventing against relapse or recurrence of acute mood episodes in adolescent patients diagnosed with bipolar disorder.</p> <p>Methods</p> <p>Consenting patients meeting DSM-IV lifetime criteria for a bipolar disorder and clinically appropriate for maintenance treatment were enrolled in a 48-week open prospective study. After being acutely stabilized (CGI-S ≤ 3 for 4 consecutive weeks), patients were started or continued on quetiapine and other medications were weaned off over an 8-week period. Quetiapine monotherapy was continued for 40-weeks and other mood stabilizers or antidepressants were added if clinically indicated. A neurocognitive test battery assessing the most reliable findings in adult patients was administered at fixed time points throughout the study to patients and matched controls.</p> <p>Results</p> <p>Of the 21 enrolled patients, 18 completed the 48-week study. Thirteen patients were able to be maintained without relapse or recurrence in good quality remission on quetiapine monotherapy, while 5 patients required additional medication to treat impairing residual depressive and/or anxiety symptoms. According to symptom ratings and global functioning scores, the quality of remission for all patients was very good.</p> <p>Neurocognitive test performance over treatment was equivalent to that of a matched control group of never ill adolescents. Quetiapine was generally well tolerated with no serious adverse effects.</p> <p>Conclusion</p> <p>This study suggests that a proportion of adolescent patients diagnosed with bipolar disorder can be successfully maintained on quetiapine monotherapy. The good quality of clinical remission and preserved neurocognitive functioning underscores the importance of early diagnosis and effective stabilization.</p> <p>Clinical Trials Registry</p> <p>D1441L00024</p

Pharmacotherapy of bipolar disorder in children and adolescents: an update

Objective: 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). Methods: 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. Results: 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. Conclusions: 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

Database analysis of children and adolescents with Bipolar Disorder consuming a micronutrient formula

<p>Abstract</p> <p>Background</p> <p>Eleven previous reports have shown potential benefit of a 36-ingredient micronutrient formula (known as EMPowerplus) for the treatment of psychiatric symptoms. The current study asked whether children (7-18 years) with pediatric bipolar disorder (PBD) benefited from this same micronutrient formula; the impact of Attention-Deficit/Hyperactivity Disorder (ADHD) on their response was also evaluated.</p> <p>Methods</p> <p>Data were available from an existing database for 120 children whose parents reported a diagnosis of PBD; 79% were taking psychiatric medications that are used to treat mood disorders; 24% were also reported as ADHD. Using Last Observation Carried Forward (LOCF), data were analyzed from 3 to 6 months of micronutrient use.</p> <p>Results</p> <p>At LOCF, mean symptom severity of bipolar symptoms was 46% lower than baseline (effect size (ES) = 0.78) (<it>p </it>< 0.001). In terms of responder status, 46% experienced >50% improvement at LOCF, with 38% still taking psychiatric medication (52% drop from baseline) but at much lower levels (74% reduction in number of medications being used from baseline). The results were similar for those with both ADHD and PBD: a 43% decline in PBD symptoms (ES = 0.72) and 40% in ADHD symptoms (ES = 0.62). An alternative sample of children with just ADHD symptoms (n = 41) showed a 47% reduction in symptoms from baseline to LOCF (ES = 1.04). The duration of reductions in symptom severity suggests that benefits were not attributable to placebo/expectancy effects. Similar findings were found for younger and older children and for both sexes.</p> <p>Conclusions</p> <p>The data are limited by the open label nature of the study, the lack of a control group, and the inherent self-selection bias. While these data cannot establish efficacy, the results are consistent with a growing body of research suggesting that micronutrients appear to have therapeutic benefit for children with PBD with or without ADHD in the absence of significant side effects and may allow for a reduction in psychiatric medications while improving symptoms. The consistent reporting of positive changes across multiple sites and countries are substantial enough to warrant a call for randomized clinical trials using micronutrients.</p

Can emotional and behavioral dysregulation in youth be decoded from functional neuroimaging?

Introduction High comorbidity among pediatric disorders characterized by behavioral and emotional dysregulation poses problems for diagnosis and treatment, and suggests that these disorders may be better conceptualized as dimensions of abnormal behaviors. Furthermore, identifying neuroimaging biomarkers related to dimensional measures of behavior may provide targets to guide individualized treatment. We aimed to use functional neuroimaging and pattern regression techniques to determine whether patterns of brain activity could accurately decode individual-level severity on a dimensional scale measuring behavioural and emotional dysregulation at two different time points. Methods A sample of fifty-seven youth (mean age: 14.5 years; 32 males) was selected from a multisite study of youth with parent-reported behavioral and emotional dysregulation. Participants performed a block-design reward paradigm during functional Magnetic Resonance Imaging (fMRI). Pattern regression analyses consisted of Relevance Vector Regression (RVR) and two cross-validation strategies implemented in the Pattern Recognition for Neuroimaging toolbox (PRoNTo). Medication was treated as a binary confounding variable. Decoded and actual clinical scores were compared using Pearson's correlation coefficient (r) and mean squared error (MSE) to evaluate the models. Permutation test was applied to estimate significance levels. Results Relevance Vector Regression identified patterns of neural activity associated with symptoms of behavioral and emotional dysregulation at the initial study screen and close to the fMRI scanning session. The correlation and the mean squared error between actual and decoded symptoms were significant at the initial study screen and close to the fMRI scanning session. However, after controlling for potential medication effects, results remained significant only for decoding symptoms at the initial study screen. Neural regions with the highest contribution to the pattern regression model included cerebellum, sensory-motor and fronto-limbic areas. Conclusions The combination of pattern regression models and neuroimaging can help to determine the severity of behavioral and emotional dysregulation in youth at different time points. Copyright: &copy; 2016 Portugal et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Controversies concerning the diagnosis and treatment of bipolar disorder in children

This commentary grows out of an interdisciplinary workshop focused on controversies surrounding the diagnosis and treatment of bipolar disorder (BP) in children. Although debate about the occurrence and frequency of BP in children is more than 50 years old, it increased in the mid 1990s when researchers adapted the DSM account of bipolar symptoms to diagnose children. We offer a brief history of the debate from the mid 90s through the present, ending with current efforts to distinguish between a small number of children whose behaviors closely fit DSM criteria for BP, and a significantly larger number of children who have been receiving a BP diagnosis but whose behaviors do not closely fit those criteria. We agree with one emerging approach, which gives part or all of that larger number of children a new diagnosis called Severe Mood Dysregulation or Temper Dysregulation Disorder with Dysphoria

Early stages of bipolar disorder: characterization and strategies for early intervention

Objective: To characterize the early stages of bipolar disorder (BD), defined as the clinical prodrome/subsyndromal stage and first-episode phase, and strategies for their respective treatment. Methods: A selective literature search of the PubMed, Embase, PsycINFO, and ISI databases from inception until March 2014 was performed. Included in this review were articles that a) characterized prodromal and first-episode stages of BD or b) detailed efficacy and safety/tolerability of interventions in patients considered prodromal for BD or those with only one episode of mania/hypomania. Results: As research has only recently focused on characterization of the early phase of BD, there is little evidence for the effectiveness of any treatment option in the early phase of BD. Case management; individual, group, and family therapy; supportive therapy; and group psychoeducation programs have been proposed. Most evidence-based treatment guidelines for BD do not address treatment specifically in the context of the early stages of illness. Evidence for pharmacotherapy is usually presented in relation to illness polarity (i.e., manic/mixed or depressed) or treatment phase. Conclusions: Although early recognition and treatment are critical to preventing unfavorable outcomes, there is currently little evidence for interventions in these stages of BD