Biomedical subjects

Joseph Biederman

Publications and source records attributed to Joseph Biederman.

At least 199 records · Page 11Linked to original sources

PubMed2002

Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial.

OBJECTIVE: To assess the comparability of atomoxetine, a new therapy for attention-deficit/hyperactivity disorder (ADHD) and methylphenidate. (Atomoxetine was originally called tomoxetine. The name was recently changed in order to avoid any potential confusion with tamoxifen that might lead to errors in dispensing drug.) METHOD: Children with ADHD were randomized to open-label atomoxetine or methylphenidate for 10 weeks. Response was assessed with the ADHD-IV Rating Scale. RESULTS: Two hundred twenty-eight patients were randomized (atomoxetine n = 184, methylphenidate n = 44). Both drugs were associated with marked improvement in inattentive and hyperactive-impulsive symptom clusters as assessed by parents and investigators. No statistically significant differences between treatment groups were observed on the primary outcome measure (investigator-rated ADHD-IV Rating Scale total score: atomoxetine baseline: 39.4 [8.5], endpoint: 20.0 [13.9]; methylphenidate baseline: 37.6 [9.7], endpoint: 19.8 (16.6); p = .66). Safety and tolerability were also similar between the 2 drugs. Discontinuations due to adverse events were 10/184 (5.4%) for atomoxetine and 5/44 (11.4%) for methylphenidate; p = .175. CONCLUSION: These data provide preliminary evidence that atomoxetine is associated with therapeutic effects comparable to those of methylphenidate.

Adolescent↗

PubMed2002

An open-label trial of divalproex in children and adolescents with bipolar disorder.

OBJECTIVE: This study evaluated the safety and effectiveness of divalproex sodium (Depakote ) in the treatment of youths with bipolar disorder. METHOD: Forty bipolar disorder patients aged 7 to 19 years, with a manic, hypomanic, or mixed episode, enrolled in an open-label study of divalproex (2-8 weeks), followed by a double-blind, placebo-controlled period (8 weeks). RESULTS: Twenty-two subjects (61%) showed > or =50% improvement in Mania Rating Scale (MRS) scores during the open-label period. Significant ( <.001) improvements from baseline were seen for mean scores of all efficacy measures, including the MRS, Manic Syndrome Scale, Behavior and Ideation Scale, Brief Psychiatric Rating Scale, Clinical Global Impressions Severity scale, and Hamilton Rating Scale for Depression. Of the 23 subjects who discontinued the study during the open-label period, 6 (15%) discontinued for ineffectiveness, 6 (15%) for intolerance, 6 (15%) for noncompliance, and 6 (15%) for other reasons. Adverse events were generally mild or moderate in severity, with the most common being headache, nausea, vomiting, diarrhea, and somnolence. Laboratory data results were unremarkable. Too few subjects participated in the double-blind period for statistical analysis. CONCLUSION: This study provides preliminary support for the safety and effectiveness of divalproex in the treatment of bipolar disorder in youths.

Adolescent↗

PubMed2002

Impact of low birth weight on attention-deficit hyperactivity disorder.

The objective of the study was to evaluate an association between low birth weight (LBW) and attention-deficit hyperactivity disorder (ADHD) attending to potential family-genetic and environmental confounders. We examined 252 ADHD cases (boys and girls) and 231 non-ADHD controls and their parents. All subjects were extensively assessed with structured diagnostic interviews, cognitive assessments, and structured interviews of prenatal, infancy, and delivery complications. ADHD cases were three times more likely to have been born LBW than were non-ADHD controls, after attending to potential confounders such as prenatal exposure to alcohol and cigarettes, parental ADHD, social class, and comorbid disruptive behavior disorders in parents and offspring. If this association was causal, 13.8% of all ADHD cases could be attributed to LBW. These results converge with prior studies documenting similar associations and indicate that LBW is an independent risk factor for ADHD. Children with LBW, however, make up a relatively small proportion of children with ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2002

Patterns of psychopathology and dysfunction in clinically referred preschoolers.

Despite the growing interest in the use of psychotropic medications in preschoolers, little is known about the clinical presentation of young children referred for psychiatric services. We describe the clinical characteristics, psychiatric disorders, and functioning of preschoolers referred for pediatric psychiatry evaluation. Structured psychiatric interviews assessing lifetime psychopathology by DSM-III-R criteria were completed on clinically referred youth. Family, social, and overall functioning were assessed at intake. From the pool of 1658 consecutive referrals, we identified 200 children less than or equal to (<or=) 6 years of age (12%). The most common psychopathology identified was attention deficit hyperactivity disorder (ADHD) (86%), followed by other disruptive behavioral (61%), mood (43%), and anxiety disorders (28%). Co-occurring psychiatric disorders were common with preschoolers manifesting a mean of two major psychiatric disorders per child. Despite their young age, the onset of psychopathology preceded evaluation by a mean (+/-SD) of 2.2 +/- 1.3 years. Preschoolers referred for psychiatric services had high rates of psychopathology with prominent comorbidity and associated dysfunction. These preschoolers are likely to require aggressive interventions including psychopharmacology.

Anxiety Disorders↗

PubMed2002

Comparative efficacy of Adderall and methylphenidate in attention-deficit/hyperactivity disorder: a meta-analysis.

Because methylphenidate is currently the most widely prescribed medication for attention-deficit/ hyperactivity disorder, several studies have used it as the active comparator medication for evaluating the efficacy of a newer stimulant, Adderall. These prior studies show Adderall to be superior to placebo and suggest it is at least as effective as the standard-release form of methylphenidate and has a longer duration of action. Although these initial studies provide useful information for clinicians treating children with attention-deficit/hyperactivity disorder, they are difficult to interpret because findings vary among studies and among the different types of measures used within each study. To provide a clearer picture of what conclusions can be drawn from these studies, we performed a meta-analysis. Data from the four available studies suggest that Adderall has a small but statistically significant advantage over the standard-release form of methylphenidate. This advantage was observed for both symptom measures and global ratings but was strongest for global ratings. The effect of Adderall was significant for clinician and parent ratings but not for teacher ratings and was significant for both fixed-dose and best-dose designs.

Adolescent↗

PubMed2002

Fluoxetine pharmacokinetics in pediatric patients.

The objective of this study was to evaluate the pharmacokinetic profile of fluoxetine (FLX) and its major metabolite, norfluoxetine (NORFLX), in children and adolescent patients undergoing psychiatric treatment. Twenty-one pediatric subjects--10 children (6-12 years) and 11 adolescents (13-18 years)--were administered 20 mg FLX for 60 days, with sparse blood samples taken throughout the open-label study. Subjects contributed 168 plasma concentrations. Pharmacokinetic parameters were estimated using a mixed effects nonlinear model. Mean steady-state FLX and NORFLX of 127 ng/mL and 151 ng/mL, respectively, were achieved in children and adolescents after 4 weeks of treatment, with high between-patient variability. FLX was 2-fold higher and NORFLX was 1.7-fold higher in children relative to adolescents; however, when normalized to body weight, FLX and NORFLX were similar for both age groups. Age, body weight, body mass index, and body surface area, modeled independently as continuous variables, significantly improved the population pharmacokinetic model when evaluated as patient factors. Body weight was the covariate retained in the final model. In conclusion, children have 2-fold higher FLX and NORFLX relative to adolescents that appear to be related to indices of body size. The accumulation profile and steady-state concentrations in adolescents appear similar to those in adults.

Adolescent↗

PubMed2002

Dopamine transporter gene and response to methylphenidate in attention-deficit/hyperactivity disorder.

This study aims to evaluate whether a previously reported association between homozygosity for the 10-repeat allele of the dopamine transporter gene (10/10) and poor response to methylphenidate (MPH) would be replicated in a sample of Brazilian attention deficit/hyperactivity disorder (ADHD) boys. In a blind naturalistic study, 50 male ADHD youths were treated with MPH. Efficacy of the medication was measured by means of the 10-item Conners Abbreviated Rating Scale (ABRS), and the Children's Global Assessment Scale (CGAS). While 75% (15/20) of the youths without 10/10 genotype demonstrated an improvement higher than 50% in the ABRS scores with MPH, only 47% (14/30) of the subjects with 10/10 genotype achieved the same level of improvement with medication (one-tailed P = 0.04). In addition, the group without this genotype had significantly higher increase in the CGAS scores than the other group (one-tailed P < 0.01). Our findings support an association between homozygosity for the 10-repeat allele at dopamine transporter gene locus and poor response to MPH.

Adolescent↗

PubMed2002

Attention deficit/hyperactivity disorder across the lifespan.

Attention deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder presenting for treatment in youth. ADHD is often chronic with prominent symptoms and impairment spanning into adulthood. ADHD is often associated with co-occurring anxiety, mood, and disruptive disorders, as well as substance abuse. The diagnosis of ADHD by careful review of symptoms and impairment is both reliable and valid. Recent genetic, imaging, neurochemistry, and neuropsychological data support the biological underpinning of the disorder. All aspects of an individual's life must be considered in the diagnosis and treatment of ADHD. Pharmacotherapy, including stimulants, antidepressants, and antihypertensives, plays a fundamental role in the management of ADHD across the lifespan.

Adolescent↗

PubMed2002

Influence of gender on attention deficit hyperactivity disorder in children referred to a psychiatric clinic.

OBJECTIVE: The substantial discrepancy in the male-to-female ratio between clinic-referred (10 to 1) and community (3 to 1) samples of children with attention deficit hyperactivity disorder (ADHD) suggests that gender differences may be operant in the phenotypic expression of ADHD. In this study the authors systematically examined the impact of gender on the clinical features of ADHD in a group of children referred to a clinic. METHOD: The study included 140 boys and 140 girls with ADHD and 120 boys and 122 girls without ADHD as comparison subjects. All subjects were systematically assessed with structured diagnostic interviews and neuropsychological batteries for subtypes of ADHD as well as emotional, school, intellectual, interpersonal, and family functioning. RESULTS: Girls with ADHD were more likely than boys to have the predominantly inattentive type of ADHD, less likely to have a learning disability, and less likely to manifest problems in school or in their spare time. In addition, girls with ADHD were at less risk for comorbid major depression, conduct disorder, and oppositional defiant disorder than boys with ADHD. A statistically significant gender-by-ADHD interaction was identified for comorbid substance use disorders as well. CONCLUSIONS: The lower likelihood for girls to manifest psychiatric, cognitive, and functional impairment than boys could result in gender-based referral bias unfavorable to girls with ADHD.

Adolescent↗

PubMed2002

Psychiatric comorbidity, family dysfunction, and social impairment in referred youth with oppositional defiant disorder.

OBJECTIVE: The authors sought to achieve an improved understanding of the diagnosis of oppositional defiant disorder independent of its association with conduct disorder. METHOD: Family interactions, social functioning, and psychiatric comorbidity were compared in clinically referred male and female subjects with oppositional defiant disorder alone (N=643) or with comorbid conduct disorder (N=262) and a psychiatric comparison group with neither oppositional defiant disorder nor conduct disorder (N=695). RESULTS: Oppositional defiant disorder youth with or without conduct disorder were found to have significantly higher rates of comorbid psychiatric disorders and significantly greater family and social dysfunction relative to psychiatric comparison subjects. Differences between subjects with oppositional defiant disorder alone and those with comorbid conduct disorder were seen primarily in rates of mood disorders and social impairment. Oppositional defiant disorder was a significant correlate of adverse family and social outcomes when comorbid disorders (including conduct disorder) were controlled. CONCLUSIONS: These results support the validity of the oppositional defiant disorder diagnosis as a meaningful clinical entity independent of conduct disorder and highlight the extremely detrimental effects of oppositional defiant disorder on multiple domains of functioning in children and adolescents.

Adolescent↗

PubMed2002

Differential effect of environmental adversity by gender: Rutter's index of adversity in a group of boys and girls with and without ADHD.

OBJECTIVE: This study examined the effect of gender in mediating the association between environmental adversity and the risk of attention deficit hyperactivity disorder (ADHD) and associated impairments. METHOD: The authors studied 280 ADHD and 242 healthy comparison probands of both genders who were between the ages of 6 and 17 years. They tested the association between Rutter's indicators of adversity (including family conflict, social class, family size, maternal psychopathology, and paternal criminality) and ADHD, comorbidity, and functioning. RESULTS: Greater levels of environmental adversity were associated with a greater risk for ADHD and other comorbidity in both genders in a dose-dependent fashion. However, learning disability and global functioning were modified by gender, with more detrimental effects observed in boys than in girls. Low social class, maternal psychopathology, and family conflict were significantly associated with psychopathology and functional impairment in the probands, with control for gender, parental ADHD, proband ADHD status, and maternal smoking during pregnancy. CONCLUSIONS: Psychosocial adversity in general and low social class, maternal psychopathology, and family conflict in particular increased the risk for ADHD and associated morbidity independently of gender and other risk factors, but gender modified the risk for adverse cognitive and interpersonal outcomes; boys were more vulnerable to the disorder than girls. Because of the difficulties in separating the effects of genetics from environment, these results must be interpreted as provisional until confirmation from twin and adoption studies.

Adolescent↗

PubMed2002

Correlates of ADHD among children in pediatric and psychiatric clinics.

OBJECTIVE: Conventional wisdom among pediatricians has been that children with attention-deficit hyperactivity disorder (ADHD) who receive their diagnosis and are managed in the primary care setting have fewer comorbid psychiatric disorders and milder impairments than those seen in psychiatric clinics. The authors sought to determine whether comorbidity and clinical correlates of ADHD differ among children in these two settings. METHODS: A case-control study design was used. Participants were 522 children and adolescents of both sexes, six to 18 years of age, with (N=280) and without (N=242) ADHD. Participants were drawn from pediatric and psychiatric clinics in a tertiary care hospital and a health maintenance organization in a large metropolitan area. Assessments were conducted with standardized measures of psychiatric, cognitive, social, academic, and family function. RESULTS: The number, type, clusters, and age at onset of ADHD symptoms were nearly identical for youths at pediatric and psychiatric ascertainment sources. Regardless of source, participants with ADHD were significantly more likely than controls to have a higher prevalence of mood disorders, other disruptive behavior, anxiety disorders, and substance use disorders. Significant impairments of intellectual, academic, interpersonal, and family functioning did not differ between ascertainment sources. CONCLUSIONS: Children with ADHD from both psychiatric and pediatric practices have prototypical symptoms of the disorder; high levels of comorbidity with mood, anxiety, and disruptive behavior disorders; and impairments in cognitive, interpersonal, and academic function that do not differ by ascertainment source. These findings suggest that children cared for in pediatric practice have similar levels of comorbidity and dysfunction as psychiatrically referred youth.

Adolescent↗

PubMed2002

A review of the pharmacotherapy of adults with attention-deficit/hyperactivity disorder.

OBJECTIVE: Despite the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults, the use of pharmacotherapeutics remains less established. METHODS: A systematic review of the literature identified 15 studies (N = 435 subjects) of stimulants, and 22 studies of non-stimulant medications (N = 421 subjects) including antidepressants, antihypertensives, amino acids, and wake-promoting agents for the treatment of ADHD in adults. RESULTS: Studies with stimulants and antidepressants demonstrated significant short-term improvement in ADHD symptoms compared to placebo in adults. Methylphenidate (MPH) and amphetamine had an immediate onset of action whereas the ADHD response to pemoline and antidepressants appeared delayed. The response to amphetamine and MPH appears to be dose-dependent. Controlled data on nicotonic and noradrenergic compounds appear promising. There was considerable variability in diagnostic criteria, dosing parameters, and response rates between the various studies. CONCLUSIONS: Under controlled conditions, the aggregate literature shows that the stimulants and noradrenergic antidepressants had a clinically and statistically significant beneficial effect on treating ADHD in adults.

Adult↗

PubMed2002

Further evidence for the diagnostic continuity between child and adolescent ADHD.

OBJECTIVE: To determine if there are differences in the clinical expression and correlates of ADHD between children and adolescents. METHOD: Subjects were 811 boys and girls aged 6 to 17 with ADHD, and 132 gender- and age-matched controls. Blind raters, using DSM-III-R structured diagnostic interviews and psychometric measures, assessed psychiatric diagnoses, intellectual performance, social disability, and school failure. RESULTS: Children and adolescents with ADHD had very similar patterns of outcome in multiple domains of assessment, including comorbidity with conduct, mood and anxiety disorders, and school functioning. There was some evidence that the rate of ODD was greater in adolescents compared to children, and that this difference was greater in the control sample. CONCLUSIONS: These findings document the diagnostic continuity of ADHD between childhood and adolescence and support the inclusion of adolescent samples in ADHD research protocols.

Adolescent↗

PubMed2002

A randomized, double-blind, placebo-controlled, parallel-group study of SLI381 (Adderall XR) in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: SLI381 (Adderall XR) is a 2-component extended-release capsule formulation of Adderall designed to produce a therapeutic effect that lasts throughout the day with 1 morning dose. The primary objective of this study was to assess the efficacy and safety of SLI381 compared with placebo in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children in a naturalistic school and home setting. A secondary objective was to assess the diurnal variation in responses based on morning and afternoon assessments. METHODS: A multicenter, randomized, double-blind, parallel-group, placebo-controlled trial was conducted at 47 sites. After a 1-week washout of any previous stimulant medication, patients were randomized to receive single-daily morning doses of placebo or SLI381 10 mg, 20 mg, or 30 mg for 3 weeks. Participants aged 6 to 12 years inclusive who satisfied Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria diagnosis of ADHD were included. The primary efficacy parameter was the Conners Global Index Scale for Teachers. Secondary efficacy parameters included the Conners Global Index Scale for Parents, the Clinical Global Impressions Scale for improvement, and the Parent Global Assessment for improvement. Safety was assessed by recording adverse events, laboratory tests, and vital signs at each visit during the study. Physical examinations and electrocardiograms were performed at the screening and the end of the study. RESULTS: Five hundred eighty-four children were randomized, 563 were included in the intent-to-treat population, and 509 completed the entire study. Intention-to-treat analysis of Conners Global Index Scale for Teachers and Conners Global Index Scale for Parents scores revealed significant improvement in morning, afternoon, and late afternoon behavior for all active treatment groups versus placebo. All active treatment groups showed significant dose-related improvement in behavior from baseline. Both the Clinical Global Impressions Scale for improvement and Parent Global Assessment for improvement showed all doses of SLI381 to be superior to placebo at treatment end and both confirmed the dose-response relationship between improvement and the SLI381 dose. The incidence of spontaneously reported adverse events was low and similar for active treatments and placebo. CONCLUSIONS: SLI381 produced consistent, dose-related improvements on all measures of efficacy. The extended-release nature of the SLI381 formulation was shown by continued, significant improvement in afternoon assessments by teachers and afternoon and late afternoon assessments by parents. The time course and therapeutic effects of SLI381 suggests that this medication is an efficacious once-daily treatment for children with ADHD.

Amphetamines↗

PubMed2002

Efficacy of atomoxetine versus placebo in school-age girls with attention-deficit/hyperactivity disorder.

OBJECTIVE: The efficacy of atomoxetine was assessed in school-age girls with attention-deficit/hyperactivity disorder (ADHD). Atomoxetine is a potent inhibitor of the presynaptic norepinephrine transporter with minimal affinity for other noradrenergic receptors or for other neurotransmitter transporters or receptors. METHODS: A total of 291 children who were 7 to 13 years of age and met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for ADHD participated in 1 of 2 combined, double-blind, placebo-controlled, multisite, identical clinical trials. This intent-to-treat subset analysis examined the effects of atomoxetine versus placebo in 51 girls who were randomized to atomoxetine (n = 30) or placebo (n = 21) for 9 weeks. ADHD symptoms were assessed using parent- and investigator-rated scales. RESULTS: Atomoxetine was superior to placebo on the following measures: the Attention-Deficit Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator Administered and Scored Total Score; the Inattentive and Hyperactive/Impulsive subscales of the Attention-Deficit Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator Administered and Scored Total Score; the ADHD Index subscale of the Conners' Parent Rating Scale-Revised: Short Form; and the Clinical Global Impressions of Severity of ADHD. Statistically significant efficacy was seen 1 week after randomization and remained so for the duration of the study. One patient from each of the atomoxetine and placebo groups discontinued the study as a result of an adverse event. CONCLUSION: Atomoxetine was found to be effective and well tolerated for the treatment of ADHD in school-age girls.

Adolescent↗

PubMed2002

Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder.

BACKGROUND: Atomoxetine is a nonstimulant drug being studied for the treatment of attention-deficit/hyperactivity disorder (ADHD). Atomoxetine is a highly specific inhibitor of the presynaptic norepinephrine transporter with minimal affinity for other noradrenergic receptors or other neurotransmitter transporters or receptors. Results of 2 proof-of-concept studies are reported that tested the hypothesis that a selective inhibitor of presynaptic norepinephrine uptake would be effective for the treatment of ADHD in school-aged children. METHOD: Two identical 12-week, stratified, randomized, double-blind, placebo-controlled trials were conducted in children who met DSM-IV criteria for ADHD. The primary efficacy outcome measure was the mean change from baseline to endpoint in the Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD RS) total score. Secondary efficacy measures included the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) and the Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S). RESULTS: A total of 291 patients were randomized in the 2 trials combined (Study 1, N = 147; Study 2, N = 144). Stimulant-naive patients were randomized to atomoxetine, placebo, or methylphenidate. Patients with prior stimulant exposure were randomized to atomoxetine or placebo. Atomoxetine significantly reduced ADHD RS total scores compared with placebo in each study (p <.001). Changes in the CGI-ADHD-S (Study 1: p =.003; Study 2: p =.001) and CPRS-ADHD Index (Study 1: p =.023; Study 2: p <.001) also showed atomoxetine to be statistically significantly superior to placebo in reducing ADHD symptoms. Atomoxetine was found to be well tolerated in this population of pediatric patients. CONCLUSION: Two studies of atomoxetine early in its development confirmed that atomoxetine, a specific and selective inhibitor of noradrenergic uptake, was effective for the treatment of children with ADHD. In addition, atomoxetine was found to be well tolerated.

Antidepressive Agents↗

PubMed2002

Overview and neurobiology of attention-deficit/hyperactivity disorder.

Although attention-deficit/hyperactivity disorder (ADHD) impairs millions of people worldwide, both the prevalence and existence of the disorder are being reevaluated at the phenotypic level. To safeguard against overdiagnosis, the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), demands that individuals with ADHD have pervasive impairment, that is, impairment in more than 1 setting. However, the appropriateness of the DSM-IV classification of ADHD is also undergoing reevaluation. Like the symptoms of a developmental disability, the symptoms of ADHD must be evaluated in the context of age-based norms; therefore, the current criteria for ADHD, which are not age referenced, may minimize the rate of persistence of ADHD into adulthood. In an effort to better understand the pathophysiology of ADHD, recent research has focused on identifying the etiology of ADHD. These studies have revealed that the disorder is highly heritable and may be associated with neurobiological deficits in the prefrontal cortex and related subcortical systems. Etiologic studies have also identified candidate genes and prenatal and perinatal risk factors for ADHD. As the causes and course of ADHD are better understood, a new generation of medications is being developed for the disorder. Although stimulants are often effective in reducing the symptoms of the disorder, as a class they have limitations such as a lack of 24-hour-a-day coverage, unwanted side effects, potential for abuse, and lessened effectiveness in the context of some comorbidities. Therefore, the treatment characteristics of newer, more selective treatments such as atomoxetine should continue to be explored in ADHD.

Adult↗