Cesar A. Soutullo

Diagnostic Characteristics of 93 Cases of a Prepubertal and Early Adolescent Bipolar Disorder Phenotype by Gender, Puberty and Comorbid Attention Deficit Hyperactivity Disorder

OBJECTIVE Etiopathogenetic and treatment studies require homogeneous phenotypes. Therefore, effects of gender, puberty, and comorbid attention deficit hyperactivity disorder (ADHD) on DSM-IV mania criteria and other characteristics of a prepubertal and early adolescent bipolar disorder (PEA-BP) phenotype were investigated. METHOD Consecutively ascertained PEA-BP (with or without comorbid ADHD) outpatients (n = 93) were blindly assessed by research nurses with comprehensive instruments given to mothers and children separately, consensus conferences, and offsite blind best estimates of both diagnoses and mania items. To fit the study phenotype, subjects needed to have current DSM-IV mania or hypomania with elated mood and/or grandiosity as one criterion and to be definite cases by severity ratings. RESULTS Subjects were aged 10.9 +/- 2.6 years, had current episode length of 3.6 +/- 2.5 years, and had early age of onset at 7.3 +/- 3.5 years. No significant differences were found by gender, puberty, or comorbid ADHD on rates of mania criteria (e.g., elation, grandiosity, racing thoughts), mixed mania, psychosis, rapid cycling, suicidality, or comorbid oppositional defiant disorder (ODD), with few exceptions. Subjects with comorbid ADHD were more likely to be younger and male. Pubertal subjects had higher rates of hypersexuality. CONCLUSIONS These findings support that the PEA-BP phenotype is homogeneous except for differences (hyperactivity, hypersexuality) that mirror normal development.

Worse Quality of Life for Children With Newly Diagnosed Attention-Deficit/Hyperactivity Disorder, Compared With Asthmatic and Healthy Children

Objective. To evaluate the quality of life (QOL) of untreated children with newly diagnosed attention-deficit/hyperactivity disorder (ADHD), compared with asthmatic and healthy children. Methods. This prospective, case-control study included a group of 120 children, 6 to 12 years of age, with newly diagnosed ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Subjects were matched according to age, gender, and health care area with 2 control groups, ie, 93 asthmatic children and 120 healthy children. Sociodemographic characteristics and Child Health Questionnaire scores were collected. Results. The QOL of children with ADHD was rated worse than that of asthmatic or healthy children for most Child Health Questionnaire domains. The greatest differences were found in behavior, social limitations attributable to physical problems, emotional impact on parents, and family activities. Almost every psychosocial domain was more affected in comparison with asthmatic children and both psychosocial and physical domains in comparison with healthy children. Conclusions. ADHD interferes with the daily lives of children, parents, and families even more than asthma, primarily in areas related to psychosocial functioning, although evidence of impaired physical functioning also emerged. Delays in recognition, assessment, and management of ADHD may affect negatively the QOL of those children.

Impact of attention-deficit/hyperactivity disorder on the patient and family: results from a European survey

BackgroundChildren with attention-deficit/hyperactivity disorder (ADHD) often experience problems with education, interaction with others and emotional disturbances. Families of ADHD children also suffer a significant burden, in terms of strain on relationships and reduced work productivity. This parent survey assessed daily life for children with ADHD and their families.MethodThis pan-European survey involved the completion of an on-line questionnaire by parents of children (6–18 years) with ADHD (ADHD sample) and without ADHD (normative population sample). Parents were questioned about the impact of their childs ADHD on everyday activities, general behaviour and family relationships.ResultsThe ADHD sample comprised 910 parents and the normative population sample 995 parents. 62% of ADHD children were not currently receiving medication; 15% were receiving 6–8 hour stimulant medication and 23% 12-hour stimulant medication. Compared with the normative population sample, parents reported that ADHD children consistently displayed more demanding, noisy, disruptive, disorganised and impulsive behaviour. Significantly more parents reported that ADHD children experienced challenges throughout the day, from morning until bedtime, compared with the normative population sample. Parents reported that children with ADHD receiving 12-hour stimulant medication experienced fewer challenges during early afternoon and late afternoon/early evening than children receiving 6–8 hour stimulant medication; by late evening and bedtime however, this difference was not apparent. ADHD was reported to impact most significantly on activities such as homework, family routines and playing with other children. All relationships between ADHD children and others were also negatively affected, especially those between parent and child (72% of respondents). Parents reported that more children with ADHD experienced a personal injury in the preceding 12 months, including those requiring the attention of healthcare professionals. Although 68% of parents were satisfied with their childs current treatment, 35–40% stated that their childs ADHD symptoms needed to be more effectively treated during the afternoon and evening.ConclusionThis parent survey highlights the breadth of problems experienced by ADHD children and the impact throughout the day on both activities and relationships. Therefore, there is a need for treatment approaches that take into account the 24-hour impact of the disorder and include all-day coverage with effective medication.

Six-Month Stability and Outcome of a Prepubertal and Early Adolescent Bipolar Disorder Phenotype

OBJECTIVE Six-month follow-up data are provided on a prepubertal and early adolescent bipolar disorder phenotype (PEA-BP). Stabilities were defined as continuous presence of PEA-BP and of individual mania criteria between baseline and 6 months. METHOD Baseline and 6-month assessments of consecutively ascertained PEA-BP outpatients (n = 91) included comprehensive instruments given to mothers and children, separately, by research nurses; consensus conferences; and offsite blind best estimates of both diagnoses and mania items. To fit the study phenotype, subjects needed to have current DSM-IV mania or hypomania with elated mood and/or grandiosity as one mania criterion and to be definite cases by severity ratings. RESULTS Of the 93 baseline subjects, 91 completed the 6-month assessment, for a retention rate of 97.8%. Baseline age was 10.9 +/- 2.7 years, and age of onset of current episode was 7.3 +/- 3.5 years. At 6 months, 85.7% still had full criteria and severity for mania or hypomania, and only 14.3% had recovered. Six-month stabilities of elated mood and grandiosity were high. Cox modeling and logistic regression did not show any significant effect of multiple covariates (e.g., gender, puberty, psychosis, mixed mania, rapid cycling, or naturalistic treatment). CONCLUSIONS These longitudinal stability findings provide validation of a PEA-BP phenotype. Poor outcome was consistent with similarity of PEA-BP baseline characteristics to those of treatment-resistant adult-onset mania.

A pilot trial of adjunctive gabapentin in the treatment of bipolar disorder.

Several antiepileptic drugs (AEDs) have documented efficacy in the manic phase of bipolar disorder. To investigate the efficacy, tolerability, and safety of the new AED, gabapentin, in mania, we treated nine consecutive outpatients with bipolar I or II disorder by DSM-IV criteria who were experiencing hypomanic, manic, or mixed states inadequately responsive to standard mood stabilizers with open-label, adjunctive gabapentin. Response of manic symptoms was assessed monthly as none, minimal, moderate, or marked. Of the nine patients, seven displayed a moderate or marked reduction in manic symptoms by 1 month after addition of gabapentin, and an additional patient displayed moderate improvement after 3 months. Of these eight patients, six displayed continued antimanic responses for follow-up periods ranging from 1 to 7 months. Side effects were most commonly neurological, mild, and transient. Adjunctive gabapentin may have antimanic and mood-stabilizing effects in some patients with bipolar disorder and is generally well tolerated. Controlled studies of gabapentin in bipolar disorder appear to be warranted.

Reduced antioxidant defense in early onset first-episode psychosis: a case-control study

BackgroundOur objective is to determine the activity of the antioxidant defense system at admission in patients with early onset first psychotic episodes compared with a control group.MethodsTotal antioxidant status (TAS) and lipid peroxidation (LOOH) were determined in plasma. Enzyme activities and total glutathione levels were determined in erythrocytes in 102 children and adolescents with a first psychotic episode and 98 healthy controls.ResultsA decrease in antioxidant defense was found in patients, measured as decreased TAS and glutathione levels. Lipid damage (LOOH) and glutathione peroxidase activity was higher in patients than controls. Our study shows a decrease in the antioxidant defense system in early onset first episode psychotic patients.ConclusionsGlutathione deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in early-onset schizophrenia. Oxidative damage is present in these patients, and may contribute to its pathophysiology.

The child and adolescent first-episode psychosis study (CAFEPS): Design and baseline results ☆

OBJECTIVE The child and adolescent first-episode psychosis study (CAFEPS) is a multicenter, two-year, longitudinal project aiming to evaluate different clinical, neuropsychological, neuroimaging, biochemical, immunological, and genetic variables and treatment and prognostic factors in these patients. This paper describes the methods and rationale behind the study and the general characteristics of the sample. METHOD At six different centers, from March 2003 through November 2005, we consecutively recruited 110 patients, ages 9-17 years, who presented with a first psychotic episode. Controls were recruited from the same geographic areas and were matched for gender and age. RESULTS Patients had lower socioeconomic status (SES) (p=0.018) and parental years of education (p<0.001) than controls. The percentage of patients recruited increased with age (p<0.001) and there was a higher percentage of males (p<0.001). The total mean PANSS score was 89.03+/-20.1, the positive score 23.8+/-6.5 and the negative score 20.02+/-8.8. There were no significant differences between the genders with respect to age, parental years of education, SES, or scores in premorbid adjustment or general functioning. There were statistically significant positive correlations between age and positive symptoms and between all PANSS subscales and the Disability Assessment Schedule, and negative correlations between positive symptoms and global functioning. Diagnoses after the baseline evaluation were: psychotic disorder not otherwise specified (NOS) 35.5%, schizophreniform disorder 24.5%, mood disorder with psychotic symptoms 22.7%, schizophrenia 10%, schizoaffective disorder 2.7%, and other psychotic disorders 4.5%. Patients had worse premorbid adjustment (p<0.001) and global functioning (p<0.001) than controls after controlling for SES. CONCLUSIONS Infancy and adolescence adjustment and global functioning are lower in children and adolescents with psychotic disorders than in controls, severity of symptoms are related to general disability, and the most frequent diagnoses are psychotic disorders NOS.

Olanzapine in the treatment of adolescent acute mania: a report of seven cases

BACKGROUND Clozapine may be effective in adults and adolescents with treatment-resistant bipolar disorder. Olanzapine has a receptor affinity profile similar to that of clozapine. METHODS The responses of seven consecutive adolescents (ages 12-17) with DSM-IV bipolar disorder, manic episode, treated with olanzapine were evaluated. Response to olanzapine was rated as marked, moderate, minimal, none or worse. RESULTS Five (71%) adolescents showed a marked or moderate response. The mean+/-SD olanzapine dose was 0.146+/-0.086 mg/kg/day (11+/-6 mg/day). CONCLUSION Olanzapine may have antimanic effects in some adolescents with acute mania. Controlled studies of olanzapine in adolescent bipolar disorder appear to be warranted.

European, randomized, phase 3 study of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder

This study evaluated the efficacy and safety of lisdexamfetamine dimesylate (LDX) compared with placebo in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in Europe. Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference arm. Patients (6-17 years old) with a baseline ADHD Rating Scale version IV (ADHD-RS-IV) total score ≥ 28 were randomized (1:1:1) to dose-optimized LDX (30, 50, or 70 mg/day), OROS-MPH (18, 36, or 54 mg/day) or placebo for 7 weeks. Primary and key secondary efficacy measures were the investigator-rated ADHD-RS-IV and the Clinical Global Impressions-Improvement (CGI-I) rating, respectively. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs. Of 336 patients randomized, 196 completed the study. The difference between LDX and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -18.6 (95% confidence interval [CI]: -21.5 to -15.7) (p<0.001; effect size, 1.80). The difference between OROS-MPH and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -13.0 (95% CI: -15.9 to -10.2) (p<0.001; effect size, 1.26). The proportions (95% CI) of patients showing improvement (CGI-I of 1 or 2) at endpoint were 78% (70-86), 14% (8-21), and 61% (51-70) for LDX, placebo, and OROS-MPH. The most common TEAEs for LDX were decreased appetite, headache, and insomnia. Mean changes in vital signs were modest and consistent with the known profile of LDX. LDX was effective and generally well tolerated in children and adolescents with ADHD.

A prospective, multicenter, open-label assessment of atomoxetine in non-North American children and adolescents with ADHD.

Abstract.Objective:The aim of this study was to study treatment response to atomoxetine in a large, multicenter study of non-North American patients with ADHD.Methods:A total of 604 children and adolescents with ADHD were enrolled in a 10-week open-label trial with atomoxetine prior to randomization to a double-blind relapse prevention phase at 33 sites in the United Kingdom, continental Europe, Israel, South Africa, and Australia. All patients had ADHD symptom severity at least 1.5 standard deviations above United States age and gender norms for their diagnostic subtype as measured by the investigator-scored ADHD Rating Scale (ADHD RS). Outcomes were assessed by analysis of change in the ADHD RS; functional and psychosocial outcomes were assessed using the Child Health Questionnaire (CHQ).Results:At endpoint, ADHD RS total scores decreased by an average of 56.7%, and 69% of patients were rated as having no or minimal symptoms. Significant improvement was observed in psychosocial and functional outcomes. Discontinuations attributed to adverse events were < 4%.Conclusion:These open-label data, gathered in an international setting, add to our knowledge of the value of atomoxetine in treating ADHD symptoms, as well as its safety and tolerability.