Gabriel Ferreira Pheula

Aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder: a pilot randomized clinical trial.

OBJECTIVE To assess response to treatment with aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder (ADHD). METHOD Children and adolescents were extensively assessed according to DSM-IV criteria for bipolar disorder comorbid with ADHD (n = 710). Those with this comorbidity who were acutely manic or in mixed states were randomly assigned in a 6-week double-blind, placebo-controlled trial to aripiprazole (n = 18) or placebo (n = 25). Primary outcome measures were assessed weekly and included the Young Mania Rating Scale; the Swanson, Nolan, and Pelham Scale-Version IV; and weight. Secondary outcome measures were the Clinical Global Impressions-Severity of Illness scale, the Child Mania Rating Scale-Parental Version (CMRS-P), the Childrens Depression Rating Scale-Revised, the Kutcher Adolescent Depression Scale, and adverse events. The trial was conducted at the Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil, from January 2005 to November 2007. RESULTS The group receiving aripiprazole showed a significantly greater reduction in YMRS scores (P = .02, effect size [ES] = 0.80), CMRS-P scores (P = .02; ES = 0.54), and CGI-S scores (P = .04; ES = 0.28) from baseline to endpoint than the placebo group. In addition, higher rates of response (P = .02) and remission (P = .01) were found for the aripiprazole group. No significant between-group differences were found in weight, ADHD symptoms, and depressive symptoms. Adverse events significantly more frequent in the aripiprazole group were somnolence and sialorrhea. CONCLUSION Aripiprazole was effective in reducing manic symptoms and improving global functioning without promoting severe adverse events or weight gain. No significant treatment effect in ADHD symptoms was observed. Studies are needed to assess psychopharmacologic interventions for improving ADHD symptoms in juvenile bipolar disorder comorbid with ADHD. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00116259.

Methylphenidate Combined with Aripiprazole in Children and Adolescents with Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder: A Randomized Crossover Trial

In clinical samples, juvenile bipolar disorder (JBPD) is frequently accompanied by co-morbid attention-deficit/hyperactivity disorder (ADHD). Clinical trials assessing combined psychopharmacological interventions in this population are scarce, and methylphenidate (MPH) may worsen manic symptoms. We conducted a randomized crossover trial with MPH and placebo (2 weeks each) combined with aripiprazole in children and adolescents (n = 16; 8-17 years old) with JBPD and ADHD who had a significant response in manic symptoms with aripiprazole but still presented clinically significant symptoms of ADHD. ADHD, manic, and depressive symptoms were assessed by means of standard scales. Fourteen out of the 16 subjects completed the trial. No significant differences between the effects of methylphenidate and placebo were detected in ADHD (F(1, 43.22) = 0.00; p = 0.97) or manic (F(1, 40.19) = 0.93; p = 0.34) symptoms. Significant improvement in depressive symptoms was observed in the MPH group (F(1,19.03) = 7.75; p = 0.01) according to a secondary self-reported outcome measure. One patient using aripiprazole and MPH discontinued the trial due to the onset of a severe mixed episode. No other significant adverse events were observed. Although MPH did not worsen manic symptoms, it was not more effective than placebo in improving ADHD symptoms in children and adolescents with JBPD co-morbid with ADHD stabilized with aripiprazole. Further investigations are warranted. This study is registered at www.clinicaltrials.gov under the identifier NCT00305370.

An open-label trial of escitalopram in children and adolescents with social anxiety disorder.

Social anxiety disorder (SAD) is a highly prevalent and disabling disorder in children and adolescents. This study was designed to evaluate the efficacy and safety of a highly potent and selective serotonin reuptake inhibitor, escitalopram, in the treatment of SAD in children and adolescents. Twenty outpatients with a primary diagnosis of SAD were treated in a 12-week open trial with escitalopram. The primary outcome variable was the change from baseline to end point in Clinical Global Impression-Improvement scale (CGI-I). Secondary efficacy measures included the CGI-Severity scale (CGI-S), the Social Phobia and Anxiety Inventory for Children (SPAI-C), the Screen for Child and Anxiety Related Emotional Disorders (SCARED)-Child and Parent version, and The Youth Quality of Life Instrument-Research Version (Y-QOL-R). On the CGI-I scale, 13 of 20 patients (65%) had a score < or =2, meaning response to treatment. All symptomatic and quality of life measures showed improvements from baseline to week 12, with large effect sizes ranging from 0.9 to 1.9 (all p < 0.001). Escitalopram was generally well-tolerated. These results suggest that escitalopram may be an effective and safe treatment for pediatric SAD. Future double-blind, placebo-controlled, randomized clinical trials are warranted.

An Open-Label Trial of Risperidone in Children and Adolescents with Severe Mood Dysregulation

OBJECTIVE The diagnosis and treatment of youth with severe nonepisodic irritability and hyperarousal, a syndrome defined as severe mood dysregulation (SMD), has been the focus of increasing concern and debate among clinicians and researchers. Our main objective was to assess the effectiveness of risperidone for youths with SMD. METHODS An 8-week open label trial with risperidone was conducted. We extensively assessed 97 subjects with semistructured and clinical interviews and enrolled 21 patients in the study. Risperidone was titrated from 0.5 to 3 mg/day in the first 2 weeks. Evaluations were performed at baseline and weeks 2, 4, 6, and 8. Clinical outcome measures were (1) Aberrant Behavior Checklist-Irritability Subscale, (2) Clinical Global Impressions, and (3) severity of co-morbid conditions. RESULTS We found a significant reduction of the Aberrant Behavior Checklist-Irritability scores during the trial after risperidone use (p < 0.001). The scores at week 2 (mean = 12.03; standard error [SE] = 2.94), week 4 (mean = 15.48; SE = 2.93), week 6 (mean = 12.29; SE = 2.86), and week 8 (mean = 11.28; SE = 3.06) were significantly reduced compared with the baseline mean score (mean = 25.89; SE = 2.76) (p < 0.001). We also found an improvement in attention-deficit/hyperactivity disorder, depression, and global functioning (p < 0.001). CONCLUSION Risperidone was effective in reducing irritability in SMD youth. To the best of our knowledge, this is the first psychopharmacological trial in this group of patients with positive results. Further randomized, controlled studies are needed.

Psicoterapia baseada em evidências em crianças e adolescentes

BACKGROUND: Evidence-based treatments refer to interventions that have empirical research on their behalf. Evidence-based psychological therapy have been identified as a national goal in United States, and there is now clear guidance regarding referral for major mental health conditions. OBJECTIVE: Review the effectiveness of psychosocial interventions for all major forms of mental health problems in childhood and adolescence, and the challenges to research Evidence-Based treatments. METHODS: Computerized search of Medline database from 1985 to 2005 and review bibliographies of book chapters and review articles. RESULTS: We present empirically based psychological treatments for depression, anxiety, disruptive behavior disorder, attention deficit hyperactivity and autism. CONCLUSION: Considerable progress has been made in child and adolescent psychotherapy research, as reflected in the quantity of studies and the identification of evidence-based treatments. The actual challenge include generalization to clinical practice.

BDNF Val66Met polymorphism and peripheral protein levels in pediatric bipolar disorder and attention-deficit/hyperactivity disorder.

Frontiers between pediatric bipolar disorder (PBD) and attention‐deficit/hyperactivity disorder (ADHD) are not well defined. Few studies have addressed potentially different neurobiological factors between the two disorders. Brain‐derived neurotrophic factor (BDNF) has been increasingly recognized for its etiologic and prognostic role in adult bipolar disorder (BD) studies. This study aimed to examine the BDNF gene polymorphism and potential alterations in BDNF serum levels in the pediatric ADHD patients with or without comorbid BD illness.

Does comorbid bipolar disorder increase neuropsychological impairment in children and adolescents with ADHD

OBJECTIVE To assess differences in executive functioning between children and adolescents with attention-deficit/hyperactivity disorder (ADHD) comorbid or not with bipolar disorder (BD), and to study the neuropsychological profile of subjects with the comorbidity in a clinical sample from a developing country. METHOD Case-control study comparing 23 participants with BD + ADHD and 85 ADHD-only subjects aged 6 to 17 years old. Both groups were drug-free. Executive function domains were assessed with the Stroop Test, the Wisconsin Card Sorting Test, and the Continuous Performance Test II. RESULTS The group with juvenile BD + ADHD showed a significantly worse performance on the Stroop task, including time in color (p = 0.002), time in color-word (p < 0.001), interference, number or errors in color and color-word (p = 0.001), and number of errors in word cards (p = 0.028). No between-group differences were found in other tests. CONCLUSIONS Our findings suggest that ADHD-only and ADHD + BD do not show differences in inhibitory control and set-shifting domains. However, children and adolescents with BD and comorbid ADHD show greater impairment in processing speed and interference control. This suggests a potentially higher impairment in the dorsolateral prefrontal cortex and may be a potential neuropsychological signature of juvenile BD comorbid with ADHD.