Biomedical subjects

Joseph Biederman

Publications and source records attributed to Joseph Biederman.

At least 109 records · Page 6Linked to original sources

PubMed2005

Bupropion SR for the treatment of substance-abusing outpatient adolescents with attention-deficit/hyperactivity disorder and mood disorders.

OBJECTIVE: Few studies exist on pharmacological interventions for adolescents with substance use disorders (SUD). To this end, we evaluated the response of bupropion hydrochloride sustained release (SR) in SUD adolescents with comorbid psychopathology (both attention-deficit/ hyperactivity disorder (ADHD) and a mood disorder). METHODS: Fourteen adolescent outpatients were treated naturalistically and followed openly for 6 months. Adolescents were rated using the Drug Use Screening Inventory--Revised (DUSI-R), ADHD Symptom Checklist, and the Hamilton Rating Scale for Depression (HAM-D). Clinical Global Impression (CGI) Scale scores were obtained for Substance Abuse, ADHD, Anxiety, and Depression. The ratings were completed at baseline, at month 3, and at the 6-month endpoint. Bupropion SR was initiated at 100 mg once-daily and titrated naturalistically to a maximum dose of 400 mg/day. RESULTS: Of the 14 subjects followed, 13 subjects completed 6 months of treatment. At the 6- month endpoint compared to baseline, treatment with bupropion was associated with clinical and significant reductions in DUSI scores (-39%; p < 0.05), ADHD symptom checklist (-43%; p < 0.001), HAM-D (-76%; p < or = 0.001); and reductions in the CGIs for ADHD (p < or = 0.001), depression (p < or = 0.001), and substance abuse (p < 0.05). The mean daily dose of bupropion SR was 315 mg (in divided doses). No significant adverse events were noted during the follow-up period. CONCLUSIONS: These naturalistic data suggest that bupropion is well tolerated and may be an effective medication for the treatment of substance abusing adolescents with comorbid mood disorders and ADHD.

Adolescent↗

PubMed2005

An open trial of adjunctive donepezil in attention-deficit/hyperactivity disorder.

OBJECTIVE: Despite available pharmacotherapeutics, a number of youths with attentiondeficit/ hyperactivity disorder (ADHD) continue to experience residual symptoms and prominent executive function (EF) deficits resulting in impairment in multiple domains. We sought to determine if donepezil, used adjunctively to stimulant medication, would improve residual symptoms of ADHD and EF deficits. METHODS: In a 12-week open trial, we treated 7 children and 6 adults who had ADHD and evidence of further EF deficits with adjunctive donepezil. All subjects were stabilized on stimulants, at which time donepezil was initiated at 2.5 mg daily and increased to a maximum of 10 mg over the 12-week trial. RESULTS: Of 13 subjects receiving medication, 7 completed the trial. There was no clinically or statistically significant improvement in the ADHD Rating Scale and the Executive Function Checklist, our primary outcome measures. A majority of individuals experienced nonserious adverse events. CONCLUSIONS: Results of this small open study suggest that donepezil augmentation of stimulants is not well tolerated and does not appear useful for the treatment of residual ADHD and/or EF deficits.

Adolescent↗

PubMed2005

Atomoxetine treatment in children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder.

OBJECTIVE: To examine (1) moderating effects of oppositional defiant disorder (ODD) on attention-deficit/hyperactivity disorder (ADHD) treatment response and (2) responses of ODD symptoms to atomoxetine. METHOD: Children and adolescents (ages 8-18) with ADHD were treated for approximately 8 weeks with placebo or atomoxetine (fixed dosing: 0.5, 1.2, or 1.8 mg/kg/day, b.i.d.) under randomized, double-blind conditions. Among patients with lifetime diagnostic information (n = 293), 39% were diagnosed with comorbid ODD and 61% were not. Treatment-group differences and differences between patients with and without comorbid ODD were examined post hoc for changes on the Attention-Deficit/Hyperactivity Disorder Rating Scale IV-Parent version, investigator-administered and -scored; Conners' Parent Rating Scale-Revised Short Form; Clinical Global Impressions Severity of ADHD Scale; and the parent-rated Child Health Questionnaire. RESULTS: Youths with ADHD and comorbid ODD showed statistically significant improvement in ADHD, ODD, and quality-of-life measures. Treatment response was similar in youths with and without ODD, except that the comorbid group showed improvement compared with placebo at 1.8 mg/kg/day but not 1.2 mg/kg/day. In contrast, youths without ODD showed improvement at 1.2 mg/kg/day and no incremental benefit at 1.8 mg/kg/day. CONCLUSIONS: Atomoxetine treatment improves ADHD and ODD symptoms in youths with ADHD and ODD, although the comorbid group may require higher doses.

Adolescent↗

PubMed2005

Long-term tolerability and effectiveness of once-daily mixed amphetamine salts (Adderall XR) in children with ADHD.

OBJECTIVE: To evaluate the long-term tolerability and effectiveness of extended-release mixed amphetamine salts (MAS XR; Adderall XR) in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: This was a 24-month, multicenter, open-label extension of TWO placebo-controlled studies of MAS XR in children with ADHD aged 6 to 12 years. Subjects (N=568) began treatment with MAS XR 10 mg once daily, with 10-mg weekly dose increases to optimal effectiveness (maximum dose, 30 mg/d). Effectiveness was assessed with analysis of quarterly Conners Global Index Scale, Parent version (CGIS-P) scores. Tolerability was assessed by monitoring adverse events (AEs), vital signs, physical examinations, and serial laboratory tests. RESULTS: Significant improvements (>30%, p < .001) in CGIS-P scores were maintained during long-term treatment. Treatment was well tolerated, and most AEs were mild. The most frequently reported drug-related AEs included anorexia, insomnia, and headache. The incidence of drug-related AEs increased with increasing MAS XR dose, suggesting a dose relationship. Changes in laboratory values and vital signs were modest and not clinically meaningful. CONCLUSIONS: In children with ADHD, once-daily 10 mg-30 mg MAS XR was well tolerated and significant behavioral improvements were consistently maintained during 24 months of treatment.

Amphetamines↗

PubMed2005

Atomoxetine alone or combined with fluoxetine for treating ADHD with comorbid depressive or anxiety symptoms.

OBJECTIVE: Symptoms of depression and anxiety are commonly comorbid with attention-deficit/hyperactivity disorder (ADHD). The authors assessed the safety and effectiveness of atomoxetine monotherapy compared with combined atomoxetine/fluoxetine therapy in a population of children and adolescents with ADHD and concurrent symptoms of depression or anxiety. METHOD: Patients were randomized to treatment with fluoxetine (n = 127) or placebo (n = 46) under double-blind conditions for 8 weeks, with concomitant atomoxetine use the last 5 weeks. RESULTS: At end point, reductions in ADHD, depressive, and anxiety symptoms were marked for both treatment groups (p < .001 for the relevant scale in each symptom cluster). Some differences between treatment groups for depressive symptoms were significant, but the magnitudes of the differences were small and likely of limited clinical importance. Completion rates for the two groups were similar, as were discontinuation rates for adverse events. The combination group had greater increases in blood pressure and pulse than did the monotherapy group. CONCLUSIONS: In pediatric patients with ADHD and comorbid symptoms of depression or anxiety, atomoxetine monotherapy appears to be effective for treating ADHD. Anxiety and depressive symptoms also improved, but the absence of a placebo-only arm does not allow us to conclude that these effects are specifically the result of treatment with atomoxetine. Combined atomoxetine/fluoxetine therapy was well tolerated.

Adolescent↗

PubMed2005

Cortical gray matter differences identified by structural magnetic resonance imaging in pediatric bipolar disorder.

OBJECTIVE: Few magnetic resonance imaging (MRI) studies of bipolar disorder (BPD) have investigated the entire cerebral cortex. Cortical gray matter (GM) volume deficits have been reported in some studies of adults with BPD; this study assessed the presence of such deficits in children with BPD. METHODS: Thirty-two youths with DSM-IV BPD (mean age 11.2 +/- 2.8 years) and 15 healthy controls (HC) (11.2 +/- 3.0 years) had structured and clinical interviews, neurological examinations, neurocognitive testing, and MRI scanning on a 1.5 T GE Scanner. Image parcellation divided the neocortex into 48 gyral-based units per hemisphere, and these units were combined into frontal (FL), temporal (TL), parietal (PL), and occipital (OL) lobe volumes. Volumetric differences were examined using univariate linear regression models with alpha = 0.05. RESULTS: Relative to controls, the BPD youth had significantly smaller bilateral PL, and left TL. Analysis of PL and TL gyri showed significantly smaller volume in bilateral postcentral gyrus, and in left superior temporal and fusiform gyri, while the parahippocampal gyri were bilaterally increased in the BPD group. Although the FL overall did not differ between groups, an exploratory analysis showed that the right middle frontal gyrus was also significantly smaller in the BPD group. CONCLUSIONS: Children with BPD showed deficits in PL and TL cortical GM. Further analyses of the PL and TL found differences in areas involved in attentional control, facial recognition, and verbal and declarative memory. These cortical deficits may reflect early age of illness onset.

Adolescent↗

PubMed2005

The CBCL predicts DSM bipolar disorder in children: a receiver operating characteristic curve analysis.

BACKGROUND: No clear consensus has been reached yet on how best to characterize children who suffer from pediatric bipolar disorder (PBD). The CBCL-PBD profile on the Child Behavior Checklist (CBCL) has been consistently reported showing deviant findings on the Attention Problems, Aggressive Behavior, and Anxious-Depressed subscales. AIM: To examine the sensitivity and specificity of the proposed CBCL-PBD profile for determining DSM diagnosis of PBD. METHODS: We applied receiver operating characteristic (ROC) curve analysis to data from 471 probands from two family studies of attention-deficit hyperactivity disorder and their 410 siblings. RESULTS: The CBCL-PBD score demonstrated an area under the curve (AUC) of 0.97 for probands and 0.82 for siblings for current diagnosis of PBD, suggesting that the CBCL-PBD provided a highly efficient way of identifying subjects with a current diagnosis of PBD in this sample. CONCLUSIONS: These findings suggest that the CBCL-PBD may provide a highly efficient way of screening for childhood bipolar disorder.

Adolescent↗

PubMed2005

Are endophenotypes based on measures of executive functions useful for molecular genetic studies of ADHD?

BACKGROUND: Behavioral genetic studies provide strong evidence that attention-deficit/hyperactivity disorder (ADHD) has a substantial genetic component. Yet, due to the complexity of the ADHD phenotype, questions remain as to the specific genes that contribute to this condition as well as the pathways from genes to behavior. Endophenotypes, or phenotypes that are more closely linked to the neurobiological substrate of a disorder, offer the potential to address these two issues simultaneously (Freedman, Adler, & Leonard, 1999). Thus far, potential endophenotypes for ADHD have not been systematically studied. METHOD: The current paper reviews evidence supporting the use of deficits on neurocognitive measures of executive functions for this purpose. RESULTS: Such deficits are a correlate of ADHD and show preliminary evidence of heritability and association with relevant candidate genes. Nonetheless, studies that have assessed the familial and genetic overlap of neurocognitive impairments with ADHD have yielded inconsistent results. CONCLUSIONS: In order for executive function deficits to be used as an endophenotype for ADHD, we recommend greater attention to the neurocognitive heterogeneity of this disorder and to the precision of measurement of the neuropsychological tests employed. We also discuss empirical strategies that may be necessary to allow such research to progress prior to full resolution of the pathophysiological basis of ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

Absence of gender effects on attention deficit hyperactivity disorder: findings in nonreferred subjects.

OBJECTIVE: In a previous study, the authors found that, compared with referred boys with attention deficit hyperactivity disorder (ADHD), girls are less likely to manifest comorbid disruptive behavior disorders and learning disabilities--characteristics that could adversely affect identification of ADHD in girls. However, because referral bias can affect outcome, these findings require replication in nonreferred groups of ADHD subjects. METHOD: The authors evaluated gender effects in a large group of nonreferred siblings (N=577) of probands with ADHD and non-ADHD comparison subjects. Ninety-eight of the nonreferred siblings (N=73 males, N=25 females) met the criteria for diagnosis of ADHD, and 479 (N=244 males, N=235 females) did not meet those criteria. All siblings were systematically and comprehensively assessed with measures of emotional, school, intellectual, interpersonal, and family functioning. The assessment battery used for the siblings was the same as that used for the probands. RESULTS: The nonreferred males and females with ADHD did not differ in DSM-IV subtypes of ADHD, psychiatric comorbidity, or treatment history. They also showed similar levels of cognitive, psychosocial, school, and family functioning. CONCLUSIONS: These findings suggest that the clinical correlates of ADHD are not influenced by gender and that gender differences reported in groups of subjects seen in clinical settings may be caused by referral biases.

Adolescent↗

PubMed2005

Structural brain magnetic resonance imaging of limbic and thalamic volumes in pediatric bipolar disorder.

BACKGROUND: Youths with bipolar disorder are ideal for studying illness pathophysiology given their early presentation, lack of extended treatment, and high genetic loading. Adult bipolar disorder MRI studies have focused increasingly on limbic structures and the thalamus because of their role in mood and cognition. On the basis of adult studies, the authors hypothesized a priori that youths with bipolar disorder would have amygdalar, hippocampal, and thalamic volume abnormalities. METHOD: Forty-three youths 6-16 years of age with DSM-IV bipolar disorder (23 male, 20 female) and 20 healthy comparison subjects (12 male, eight female) similar in age and sex underwent structured and clinical interviews, neurological examination, and cognitive testing. Differences in limbic and thalamic brain volumes, on the logarithmic scale, were tested using a two-way (diagnosis and sex) univariate analysis of variance, with total cerebral volume and age controlled. RESULTS: The subjects with bipolar disorder had smaller hippocampal volumes. Further analysis revealed that this effect was driven predominantly by the female bipolar disorder subjects. In addition, both male and female youths with bipolar disorder had significantly smaller cerebral volumes. No significant hemispheric effects were seen. CONCLUSIONS: These findings support the hypothesis that the limbic system, in particular the hippocampus, may be involved in the pathophysiology of pediatric bipolar disorder. While this report may represent the largest MRI study of pediatric bipolar disorder to date, more work is needed to confirm these findings and to determine if they are unique to pediatric bipolar disorder.

Adolescent↗

PubMed2005

A simulated workplace experience for nonmedicated adults with and without ADHD.

Eighteen nonmedicated adults with attention-deficit hyperactivity disorder (ADHD) and 18 who did not have ADHD were evaluated in a full-day simulated workplace experience. It was hypothesized that adults with ADHD would evidence greater impairments on simulated tasks, off-task behavior, and self-reported ADHD symptoms than those without ADHD. Participants were compared on self-reported ADHD symptoms, objective observations, and performance on written tasks. Significant differences were noted in reading comprehension and math fluency as well as observer-rated and self-reported behavior, but not attention. The results of this study suggest that ADHD among adults is associated with significant deficits in performance of workplace tasks, internal experiences, and external observations of core symptoms of ADHD.

Adult↗

PubMed2005

Training raters to assess adult ADHD: reliability of ratings.

The standardization of ADHD ratings in adults is important given their differing symptom presentation. The authors investigated the agreement and reliability of rater standardization in a large-scale trial of atomoxetine in adults with ADHD. Training of 91 raters for the investigator-administered ADHD Rating Scale (ADHDRS-IV-Inv) occurred prior to initiation of a large, 31-site atomoxetine trial. Agreement between raters on total scores was established in two ways: (a) by Kappa coefficient (rater agreement for each item with the percentage of raters that had identical item-by-item scores) and (b) intraclass correlation coefficients (reliability). For the ADHDRS-IV-Inv, rater agreement was moderate, and reliability, as measured by Cronbach's alpha, was substantial. The data indicate that clinicians can be trained to reliably evaluate ADHD in adults using the ADHDRS-IV-Inv.

Adult↗

PubMed2005

Reexamining the familial association between asthma and ADHD in girls.

The objective of this study is to further evaluate the association between asthma and ADHD, addressing issues of familiality in female probands. A case control study of referred ADHD proband girls, controls, and relatives are used. Participants include 140 ADHD proband girls and 122 non-ADHD comparisons, with 417 and 369 first-degree biological relatives, respectively. Relatives are stratified into four groups according to proband ADHD and asthma status. The authors compare rates of asthma and ADHD in relatives. ADHD does not increase the risk for asthma in probands. Patterns of familial aggregation are mostly consistent with independent transmission of ADHD and asthma in families of girl probands. The results extend to female probands' previously reported findings that asthma and ADHD are independently transmitted in families. These findings further support the conclusion that ADHD symptoms should not be dismissed as part of asthma symptomatology or a consequence of its treatment.

Adult↗

PubMed2005

A laboratory school comparison of mixed amphetamine salts extended release (Adderall XR) and atomoxetine (Strattera) in school-aged children with attention deficit/hyperactivity disorder.

Mixed amphetamine salts extended release (MAS XR; Adderall XR) and atomoxetine (Strattera) were compared in children 6 to 12 years old with attention deficit/hyperactivity disorder (ADHD) combined or hyperactive/impulsive type in a randomized, double-blind, multicenter, parallel-group, forced-dose-escalation laboratory school study. Primary efficacy measure was the SKAMP (Swanson, Kotkin, Agler, M-Flynn, and Pelham) behavioral rating scale. Changes in mean SKAMP deportment scores from baseline were significantly greater for MAS XR (n = 102) than for atomoxetine (n = 101) overall (-0.56 and -0.13, respectively; p < .0001) and at each week (p < .001). Adverse events were similar for both treatment groups. The extended time course of action and greater therapeutic efficacy of MAS XR suggests that it is more effective than atomoxetine in children with ADHD.

Amphetamines↗

PubMed2005

What is the prevalence of adult ADHD? Results of a population screen of 966 adults.

To provide a better estimate of the prevalence of ADHD in adulthood, the authors complete a telephone survey of 966 randomly selected adults. They compute two diagnoses from the survey data. Participants meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for both childhood and adulthood are defined as narrow ADHD. Broad ADHD adds to that definition those meeting subthreshold criteria. Cronbach's alpha is .90 for the 18 DSM-IV symptoms in childhood and .88 when rated for current symptoms in adulthood. No one item unduly influences the reliability of the total score. The authors find similar results in separate analyses of hyperactive-impulsive and inattentive symptoms. They estimate prevalences of 2.9% for Narrow ADHD and 16.4% for Broad ADHD. Having ADHD is associated with lower levels of education and employment status. These findings suggest that adult ADHD is a common disorder associated with impaired functioning.

Adult↗

PubMed2005

Impact of gender and age on executive functioning: do girls and boys with and without attention deficit hyperactivity disorder differ neuropsychologically in preteen and teenage years?

ADHD is known to have neuropsychological correlates, characterized mainly by executive function (EF) deficits. However, most available data are based on studies of boys through age 12. Our goal was to assess whether girls with ADHD express neuropsychological features similar to those found in boys, and whether these impairments are found in both preteen and teen samples. Participants were 101 girls and 103 boys with DSM-III-R ADHD, and 109 comparison girls and 70 boys without ADHD, ages 9 to 17 years. Information on neuropsychological performance was obtained in a standardized manner blind to clinical status. Primary regression analyses controlled for age, socioeconomic status, learning disability, and psychiatric comorbidity. Girls and boys with ADHD were significantly more impaired on some measures of EFs than healthy comparisons but did not differ significantly from each other. With the exception of 1 test score there were no significant Sex x Diagnosis interactions. Moreover, there were no more significant interactions among age, gender, and diagnosis than would be expected by chance. Neuropsychological measures of EFs were comparably impaired in girls compared to boys with ADHD, and these impairments are found at ages 9 to 12 and ages 13 to 17. These findings suggest that executive dysfunctions are correlates of ADHD regardless of gender and age, at least through the late teen years.

Adolescent↗

PubMed2005

Effects of atomoxetine on growth after 2-year treatment among pediatric patients with attention-deficit/hyperactivity disorder.

OBJECTIVE: Treatment for attention-deficit/hyperactivity disorder is maintained typically over periods of months or years and, as a result, the potential effects on growth of pharmacotherapy for this disorder have been an area of concern. This meta-analysis examined the effect on growth of atomoxetine, now approved in the United States for the treatment of attention-deficit/hyperactivity disorder. METHODS: Patients (N = 412) were 6 to 16 years of age at the start of the treatment period and received atomoxetine treatment (maximal dose: 1.8 mg/kg per day) for >or=2 years. Weight and height measurements were analyzed both as actual values and after conversion to percentiles and z scores with growth charts from the Centers for Disease Control and Prevention. Expected weight and height at the end point were calculated through extrapolation from patients' baseline percentiles with the growth charts. RESULTS: Results indicated that, after 2 years, observed weight and height were close to those predicted on the basis of the patients' baseline weight and height. Weight increased an average of 10.8 kg, a decrease relative to baseline normative weight of 2.7 percentiles, corresponding to 0.87 kg. Height increased an average of 13.3 cm, a decrease relative to baseline normative heights of 2.2 percentiles, corresponding to 0.44 cm. For both weight and height, the quartile of patients who were smallest at baseline had an increase in end-point percentile, whereas patients in the highest quartile had a decrease. CONCLUSIONS: These findings suggested that, at the group level, there was only a minimal effect on height after 2 years of treatment with atomoxetine and, for patients most at risk (the lowest quartile), there seemed to be no effect.

Adolescent↗

PubMed2005

Efficacy and safety of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder: results of a randomized, double-blind, placebo-controlled, flexible-dose study.

OBJECTIVE: Modafinil, which is structurally and pharmacologically different from other agents that are used for the treatment of children with attention-deficit/hyperactivity disorder (ADHD), selectively activates the cortex and has low potential for abuse. Initial studies of the use of modafinil to treat ADHD showed significant improvements in the core symptoms of the disorder, namely inattention, hyperactivity, and impulsivity. This study evaluated a new formulation of modafinil (modafinil film-coated tablets) in children and adolescents with ADHD. METHODS: This 9-week, multicenter, randomized, double-blind, placebo-controlled, flexible-dose study evaluated the film-coated tablet formulation of modafinil, which was titrated to an optimal dose on the basis of efficacy and tolerability (range: 170-425 mg once daily). Efficacy was assessed by clinicians who completed the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) based on interviews with teachers (School Version) and parents (Home Version) and the Clinical Global Impression of Improvement scale. Safety evaluation was based on assessments of adverse event reports, laboratory tests, vital signs, and body weight. RESULTS: A total of 248 subjects were randomly assigned in a 2:1 ratio, and 246 were treated with modafinil (n = 164) or placebo (n = 82). Treatment groups were comparable with respect to demographics and baseline characteristics. Intention-to-treat analysis (ITT) showed that compared with placebo, treatment with modafinil significantly improved the core symptoms of ADHD as shown by greater reductions in the ADHD-RS-IV School Version total scores from baseline to final visit (mean change [SD]: -15.0 [11.8] vs -7.3 [9.7]) (effect size: 0.69; 95% confidence interval: 0.57-0.82). Significant improvements were observed with modafinil treatment on the ADHD-RS-IV School Version at week 1, with improvements maintained throughout the study. Similar differences in symptom improvements were observed on the ADHD-RS-IV Home Version between modafinil-treated and placebo-treated patients. Treatment with modafinil also significantly reduced subscale scores for inattention and hyperactivity-impulsivity on both School and Home Versions compared with placebo. At the final visit, 48% of modafinil-treated patients were rated as "much" or "very much" improved in overall clinical condition compared with 17% of placebo-treated patients (Clinical Global Impression of Improvement). Most adverse events were mild to moderate in severity, and the majority resolved during treatment. The most commonly reported adverse events in the modafinil group were insomnia (29%), headache (20%), and decreased appetite (16%). Three percent of modafinil-treated patients and 4% of placebo-treated patients discontinued treatment because of adverse events. CONCLUSIONS: Modafinil film-coated tablets significantly improved ADHD symptoms at school and home as evaluated by clinicians, teachers, and parents. Treatment with once-daily modafinil was generally well tolerated, with few discontinuations as a result of adverse events.

Adolescent↗