Carla Ruffoni Ketzer

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.

School dropout and conduct disorder in brazilian elementary school students

Objectives: To evaluate the association between DSM-IV conduct disorder (CD) and school dropout in a sample of students from the third and fourth elementary grades at state schools in the capital of the southernmost state of Brazil. Methods: In this case-control study, students that dropped out of schools (n = 44) and a control group who continued attending schools (n = 44) were assessed for CD and other prevalent mental disorders, using the Schedule for Affective Disorders and Schizophrenia for School Age Children, Epidemiological Version (K-SADS-E). Results: The prevalence of DSM-IV CD was significantly higher in the school-dropout group than in control subjects (P < 0.001), both in the entire sample and in a subsample including only subjects under age 12 years (P = 0.001). Also, the odds ratio (OR) for school dropout was significantly higher in the presence of DSM-IV CD, even after controlling for potential confounding factors (age, estimated IQ, school repetition, family structure, and income) (P < 0.01). Conclusion: Our results extend to children and young adolescents previous findings from studies of older adolescents, suggesting an association between school dropout and CD.

The acute effect of methylphenidate on cerebral blood flow in boys with attention-deficit/hyperactivity disorder

Methylphenidate (MPH) is the most commonly prescribed treatment for attention-deficit/hyperactivity disorder (ADHD). The therapeutic mechanisms of MPH are not, however, fully understood. We studied the effects of MPH on brain activity in male children and adolescents with ADHD, using the blood flow radiotracer technetium-99m ethyl cysteinate dimer (99mTc-ECD) and single-photon emission tomography (SPET) . The study was randomized, double blind, and placebo controlled (MPH group, n=19; placebo group, n=17), Radiotracer was administered during the performance of the Continuous Performance Test and before and after 4 days of MPH treatment. Statistical parametric mapping (SPM99) analysis showed a significant reduction in regional cerebral blood flow in the left parietal region in the MPH group compared with the placebo group (P<0.05, corrected for multiple comparisons). Our findings suggest that the posterior attentional system, which includes the parietal cortex, may have a role in the mediation of the therapeutic effects of MPH in ADHD.

The acute effect of methylphenidate in Brazilian male children and adolescents with ADHD: A randomized clinical trial

Objective: To evaluate the acute efficacy of methylphenidate (MPH) in Brazilian male children and adolescents with ADHD. Method: In a 4-day, double-blind, placebo-controlled, randomized, fix dose escalating, parallel-group trial, 36 ADHD children and adolescents were allocated to two groups: MPH (n = 19) and placebo (n = 17). Participants were evaluated pre- and posttreatment using the 10-item Conners Abbreviated Rating Scale (ABRS), the Children’s Global Assessment Scale (CGAS), and a simplified version of the Continuous Performance Test (CPT). Results: The MPH group had a significantly greater decrease in ABRS scores and a significantly higher increase in CGAS scores than the placebo group (p < 0.01). The MPH group showed also a significantly higher proportion of patients with a robust improvement (decrement of at least 50% in the ABRS score after the intervention) than the placebo group (p < 0.01). The MPH effect size for the ABRS was 1.05 (95% CI = 0.73-1.37). Conclusion: Our results extend the efficacy of MPH on the ADHD core symptoms extensively demonstrated in clinical trials with samples from some developed countries to a sample from a developing country where a diverse culture may modulate the clinical presentation of the disorder.

Estimated mental retardation and school dropout in a sample of students from state public schools in Porto Alegre, Brazil

OBJECTIVES: To assess the association between estimated Mental Retardation (MR) and school dropout in a sample of students of the third and fourth grades at state schools in Porto Alegre, the capital of the southernmost state of Brazil. METHOD: In this case - control study, students that dropped out from schools (n=44) and a control group who continued attending schools (n=44) had their intelligence quotient (IQ) determined by the vocabulary and cubes subtests of the Wescheler Intelligence Scale ¾ third edition (WISC¾III). Students with IQ lower than 70 were considered as potential cases of MR. Other prevalent mental disorders in this age range were assessed in both groups using the Schedule for Affective Disorders and Schizophrenia for School¾ Age Children, Epidemiological Version (K-SADS-E). RESULTS: The prevalence of potential MR was significantly higher in the dropped out group than in the control group (p<0.001). Odds ratio for school dropout was significantly higher in the presence of MR even after controlling for potentially confounding factors (age, conduct disorder, grade repetition, family structure and income) (p<0.01). CONCLUSION: Children with IQ lower than 70 (potential MR) were at higher risk for school dropout. These children need to be identified at school and specific educational strategies should be implemented to assure their inclusion in the learning process.

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.