Search PubMed⌕ Search

Biomedical subjects

James J McGough

Publications and source records attributed to James J McGough.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy and safety of dexmethylphenidate extended-release capsules in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: This multicenter, randomized, fixed-dose, double-blind, placebo-controlled study evaluated efficacy of extended-release dexmethylphenidate (d-MPH-ER) in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: Randomized adults with ADHD (n=221) received once-daily d-MPH-ER 20 mg, 30 mg, or 40 mg or placebo for 5 weeks. The primary efficacy variable was change from baseline to final visit in DSM-IV ADHD Rating Scale (ADHD-RS) total score. Secondary efficacy parameters included the proportion of patients with improvement>or=30% in ADHD-RS total score and final scores on Clinical Global Impressions-Improvement (CGI-I) scale. RESULTS: Of 218 evaluable patients, 184 completed the study. All d-MPH-ER doses were significantly superior to placebo in improving ADHD-RS total scores. Placebo scores improved by 7.9; d-MPH-ER, 20 mg, improved by 13.7 (p=.006); d-MPH-ER, 30 mg, improved by 13.4 (p=.012); and d-MPH-ER, 40 mg, improved by 16.9 (p<.001). Overall distribution of CGI-I ratings at final visit was significantly better with each d-MPH-ER dosage than with placebo. There were no unexpected safety or tolerability concerns, based on experience with racemic methylphenidate (MPH) in adults and dexmethylphenidate (d-MPH) in children. CONCLUSIONS: Once-daily d-MPH-ER at 20 mg, 30 mg, or 40 mg is a safe and effective treatment for adults with ADHD.

Adult↗
PubMed2006

A post hoc subgroup analysis of an 18-day randomized controlled trial comparing the tolerability and efficacy of mixed amphetamine salts extended release and atomoxetine in school-age girls with attention-deficit/hyperactivity disorder.

BACKGROUND: Because the scientific literature on the pharmacotherapy of attention-deficit/hyperactivity disorder (ADHD) is almost entirely based on the results of studies in samples consisting primarily of boys, much is unknown about the treatment response in girls. OBJECTIVE: This post hoc analysis compared the efficacy, tolerability, and time course of the effect of mixed amphetamine salts extended release (MAS XR) and atomoxetine in school-age girls with ADHD. METHODS: This was an intent-to-treat subanalysis of the data from girls enrolled in a multicenter, 18-day, randomized, double-blind, parallel-group, forced dose-titration, laboratory school study enrolling boys and girls aged 6 to 12 years with ADHD. The study compared the efficacy, tolerability, and time course of the effect of increasing doses of MAS XR (10, 20, and 30 mg/d) and atomoxetine (0.5 and 1.2 mg/kg per day). The laboratory school sessions were organized in cycles to include 12 hours of observation. Efficacy measures included the SKAMP (Swanson, Kotkin, Agler, M-Flynn, and Pelham) deportment rating subscale, the SKAMP attention rating subscale, and academic testing (number of math problems attempted and answered correctly). Adverse events were assessed throughout the study period. Tolerability and efficacy measures were assessed during laboratory school visits on days 7, 14, and 21. RESULTS: This subanalysis included 57 girls (median age, 9 years; 49.1% white, 22.8% black, 17.5% Hispanic) with a diagnosis of ADHD, combined subtype. Twenty-six girls were randomized to receive MAS XR and 31 were randomized to receive atomoxetine. Mean SKAMP deportment and attention subscale scores in the 2 groups were similar at baseline. Mean changes from baseline were significantly greater for MAS XR compared with atomoxetine on the SKAMP deportment score (-0.48 vs -0.04, respectively; P<0.001) and SKAMP attention score (-0.45 vs -0.05; P<0.001). The time course of medication effect, based on change from baseline in SKAMP deportment scores, indicated 12-hour efficacy for MAS XR at hours 2, 4.5, 7, 9.5, and 12 (all time points, P<0.01 vs baseline) but not for atomoxetine. At the end of the study, both treatment groups had a significant increase from baseline in the mean number of math problems attempted and answered correctly (P<0.001). Girls who received MAS XR attempted significantly greater numbers of problems compared with those who received atomoxetine (P=0.04). Both MAS XR and atomoxetine were well tolerated. The most frequently occurring treatment-related adverse events in girls receiving MAS XR were decreased appetite (40.7%), upper abdominal pain (29.6%), insomnia (25.9%), and headache (14.8%). The most frequently occurring treatment-related adverse events in girls receiving atomoxetine were somnolence (28.1%), upper abdominal pain (15.6%), vomiting (15.6%), nausea (12.5%), and decreased appetite (12.5%). CONCLUSION: This post hoc analysis in a subpopulation of girls with ADHD, combined subtype, found that 18-day treatment with MAS XR was significantly more effective than atomoxetine in terms of ratings of classroom behavior, attention, and academic productivity.

Adrenergic Uptake Inhibitors↗
PubMed2006

Once-daily OROS methylphenidate is safe and well tolerated in adolescents with attention-deficit/hyperactivity disorder.

This 8-week, open-label extension of a double-blind study reports on safety data for 171 adolescents with attention-deficit/hyperactivity disorder (ADHD) who received once-daily OROS methylphenidate (MPH) (18-72 mg/day). Headache, anorexia, and insomnia were the most frequently reported treatment-related adverse events. The incidence of adverse events was not related to dose. OROS MPH was safe and well tolerated at doses up to 72 mg/day.

Adolescent↗
PubMed2006

A randomized, double-blind, placebo-controlled, laboratory classroom assessment of methylphenidate transdermal system in children with ADHD.

OBJECTIVE: This study evaluates the efficacy, duration of action, and tolerability of methylphenidate transdermal system (MTS) in children with ADHD. METHOD: Participants were dose optimized over 5 weeks utilizing patch doses of 10, 16, 20, and 27 mg applied in the morning and worn for 9 hours. Following optimization, 80 participants were randomized to 1 week of MTS or placebo followed by 1 week of the opposite treatment. Laboratory classroom sessions conducted after each randomized week included blinded ratings of attention, behavior, and academic performance. RESULTS: MTS was well tolerated and displayed significant improvement compared with placebo. Improvements were seen at the first postdose time point measured and continued through 12 hours. CONCLUSIONS: Treatment with MTS resulted in statistically significant improvements on all efficacy measures. Time course and therapeutic effects of MTS suggest that this novel methylphenidate delivery system is an efficacious once-daily treatment for ADHD.

Administration, Cutaneous↗
PubMed2005

Atypical brain laterality in adults with ADHD during dichotic listening for emotional intonation and words.

Few studies directly examined the nature of hemispheric specialization and interaction in ADHD. The present experiment investigated left/right brain dynamics in unmedicated right handed adults with ADHD (n = 19) and in controls (n = 19), using a dichotic listening task to assess hemispheric differences in word and emotion recognition. We also assessed how focusing attention on a single ear modulated lateralized performance and affected cross-callosal interference effects. Analysis of variance indicated that ADHD subjects showed reduced left hemisphere specialization, were better at processing emotions, and worse at processing words compared to controls. These differences were eliminated during focused attention. Finally, during presumed right hemisphere processing of linguistic stimuli, subjects with ADHD showed reduced left hemisphere interference. We concluded that ADHD subjects demonstrated greater right hemisphere and reduced left hemisphere contribution during this task relative to controls. We posit that these hemispheric differences were due to management or use of available cognitive resources rather than inherent capacity.

Acoustic Stimulation↗
PubMed2005

Attention-deficit/hyperactivity disorder pharmacogenomics.

Although the efficacy of medications for attention-deficit/hyperactivity disorder (ADHD) is well demonstrated in clinical trials, substantial numbers of patients fail to remain on therapy, and there is tremendous variability in tolerability and treatment acceptance. The emerging science of pharmacogenomics seeks to identify patterns of genetic variation that will direct individually tailored treatment regimens and enhance long-term adherence. For this review, existing studies in ADHD pharmacogenomics were reviewed to assess current knowledge and provide a basis for planning future research. Twelve studies were identified. The majority investigated the role of candidate genes in predicting clinical response to methylphenidate. The most frequently studied is DAT1, although findings are inconsistent, with the 10-repeat polymorphism predicting both increased and decreased symptom reduction in various reports. Other candidates include DRD4, DRD5, DBH, 5HTT, SNAP-25, and COMT. One study was based on quantitative trait analyses in a genome-wide scan. Although interest in ADHD pharmacogenomics is encouraging, preliminary studies have been limited by small sample sizes, inconsistent research designs, retrospective reports, and a focus on symptom response. Future studies should emphasize large, prospective trials, assess multiple medications in individual subjects, and consider a full range of pharmacodynamic and pharmacokinetic outcomes.

Attention Deficit Disorder with Hyperactivity↗
PubMed2005

Short- and long-term cardiovascular effects of mixed amphetamine salts extended release in children.

OBJECTIVE: To assess the short- and long-term cardiovascular effects of once-daily treatment with a mixed amphetamine salts extended-release formulation (MAS XR; Adderall XR(R)) in children age 6 to 12 years with attention-deficit/hyperactivity disorder (ADHD). STUDY DESIGN: Short-term cardiovascular effects were assessed during a 4-week, double-blind, randomized, placebo-controlled, forced-dose-titration study of once-daily 10, 20, and 30 mg MAS XR (n = 580). Long-term cardiovascular effects were assessed in 568 subjects during a 2-year, open-label extension study of MAS XR (10 to 30 mg/day). Resting sitting blood pressure and pulse were measured at baseline and weekly during the short-term study, then monthly during long-term treatment. RESULTS: Changes in blood pressure, pulse, and QT interval corrected by Bazett's formula (QTcB) in children receiving MAS XR were not statistically significantly different than those changes seen in children receiving placebo during short-term treatment. Mean increases in blood pressure after 2 years of MAS XR treatment (systolic, 3.5 mm Hg; diastolic, 2.6 mm Hg) and pulse (3.4 bpm) were clinically insignificant, and there was no apparent dose-response relationship. CONCLUSIONS: Cardiovascular effects of short- and long-term MAS XR were minimal during short- and long-term MAS XR treatment at doses of </= 30 mg/day in otherwise healthy children.

Amphetamines↗
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

Temperament and character profiles and the dopamine D4 receptor gene in ADHD.

OBJECTIVE: This study was designed to investigate the link among attention deficit hyperactivity disorder (ADHD) in adults, novelty-seeking temperament, and the 48-base pair (bp) dopamine D4 receptor (DRD4) gene variant. METHOD: This study drew from a larger molecular genetic study of ADHD in which the ascertainment criterion was having an affected sibling pair with ADHD. Parents (N=171) from 96 families provided data. Of the 171 parents, 56 (33%) had a lifetime history of ADHD, with 28 (50%) continuing to meet DSM-IV criteria (i.e., "persistent" ADHD). Latent variable modeling was used to test whether the DRD4 gene variant or Temperament and Character Inventory factors could predict ADHD. RESULTS: Using latent variable modeling, the authors were able to confirm the first-order factor structure of the Temperament and Character Inventory. Furthermore, novelty seeking predicted ADHD lifetime diagnosis (R(2)=26%), while the DRD4 gene variant independently predicted ADHD (R(2)=5%) but not novelty seeking. CONCLUSIONS: In this unique sample of parents from multiply affected ADHD families, novelty seeking and the 48-bp DRD4 variant were associated with a lifetime history of ADHD. However, the association between novelty seeking and ADHD does not appear to be due to variation in the 48-bp DRD4 variant.

Adult↗
PubMed2005

Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology.

OBJECTIVE: Risperidone has been found efficacious for decreasing severe tantrums, aggression, and self-injurious behavior in children and adolescents with autistic disorder (autism). The authors report on whether risperidone improves the core symptoms of autism, social and communication impairment and repetitive and stereotyped behavior. METHOD: The database from an 8-week double-blind, placebo-controlled trial (N=101) and 16-week open-label continuation study (N=63) of risperidone for children and adolescents with autism was used to test for drug effects on secondary outcome measures: scores on the Ritvo-Freeman Real Life Rating Scale, the Children's Yale-Brown Obsessive Compulsive Scale, and the maladaptive behavior domain of the Vineland Adaptive Behavior Scales. RESULTS: Compared to placebo, risperidone led to a significantly greater reduction in the overall score on the Ritvo-Freeman Real Life Rating Scale, as well as the scores on the subscales for sensory motor behaviors (subscale I), affectual reactions (subscale III), and sensory responses (subscale IV). No statistically significant difference was observed, however, on the subscale for social relatedness (subscale II) or language (subscale V). Risperidone also resulted in significantly greater reductions in scores on the Children's Yale-Brown Obsessive Compulsive Scale and Vineland maladaptive behavior domain. This pattern of treatment response was maintained for 6 months. CONCLUSIONS: Risperidone led to significant improvements in the restricted, repetitive, and stereotyped patterns of behavior, interests, and activities of autistic children but did not significantly change their deficit in social interaction and communication. Further research is necessary to develop effective treatments for the core social and communicative impairments of autism.

Adolescent↗
PubMed2005

Psychiatric comorbidity in adult attention deficit hyperactivity disorder: findings from multiplex families.

OBJECTIVE: Patterns of psychiatric comorbidity were assessed in adults with and without attention deficit hyperactivity disorder (ADHD) identified through a genetic study of families containing multiple children with ADHD. METHOD: Lifetime ADHD and comorbid psychopathology were assessed in 435 parents of children with ADHD. Rates and mean ages at onset of comorbid psychopathology were compared in parents with lifetime ADHD, parents with persistent ADHD, and those without ADHD. Age-adjusted rates of comorbidity were compared with Kaplan-Meier survival curves. Logistic regression was used to assess additional risk factors for conditions more frequent in ADHD subjects. RESULTS: The parents with ADHD were significantly more likely to be unskilled workers and less likely to have a college degree. ADHD subjects had more lifetime psychopathology; 87% had at least one and 56% had at least two other psychiatric disorders, compared with 64% and 27%, respectively, in non-ADHD subjects. ADHD was associated with greater disruptive behavior, substance use, and mood and anxiety disorders and with earlier onset of major depression, dysthymia, oppositional defiant disorder, and conduct disorder. Group differences based on Kaplan-Meier age-corrected risks were consistent with those for raw frequency distributions. Male sex added risk for disruptive behavior disorders. Female sex and oppositional defiant disorder contributed to risk for depression and anxiety. ADHD was not a significant risk factor for substance use disorders when male sex, disruptive behavior disorders, and socioeconomic status were controlled. CONCLUSIONS: Adult ADHD is associated with significant lifetime psychiatric comorbidity that is not explained by clinical referral bias.

Adolescent↗
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

Dexmethylphenidate extended-release capsules for attention deficit hyperactivity disorder.

Medications for attention deficit hyperactivity disorder (ADHD) currently represent the ninth largest segment of the CNS market by sales, with 2.4 billion USD spent annually on this condition and 40% annual growth. Stimulant medications remain the most effective ADHD therapies and provide robust improvement in ADHD symptoms in both youth and adults. Current prescribing practices favor extended release preparations due to increased convenience, compliance and tolerability with once-daily dosing. Dexmethylphenidate extended release is a long-acting preparation of the ADHD medication Focalin (dexmethylphenidate immediate release) and was approved for marketing by the US Food and Drug administration in June 2005. Dexmethylphenidate consists of the single dextro-isomer form of d,l-methylphenidate commonly marketed as Ritalin. Dexmethylphenidate extended release utilizes spheroidal oral drug absorption system technology to achieve a 50% immediate medication delivery and 50% delayed release of dexmethylphenidate approximately 4 h after ingestion. Placebo-controlled, clinical trials in children and adults with ADHD have demonstrated efficacy for behavioral and academic ratings, with an analog classroom study showing medication effects up to 12 h after dosing. Dexmethylphenidate extended release was generally well tolerated with a side-effect profile similar to other stimulants. The most common reported side effects include diminished appetite and insomnia. Given its duration of effect, favorable tolerability and flexibility in dosing, dexmethylphenidate extended release is likely to gain considerable use as an ADHD treatment.

Animals↗
PubMed2004

Attention deficit hyperactivity disorder: fine mapping supports linkage to 5p13, 6q12, 16p13, and 17p11.

We completed fine mapping of nine positional candidate regions for attention-deficit/hyperactivity disorder (ADHD) in an extended population sample of 308 affected sibling pairs (ASPs), constituting the largest linkage sample of families with ADHD published to date. The candidate chromosomal regions were selected from all three published genomewide scans for ADHD, and fine mapping was done to comprehensively validate these positional candidate regions in our sample. Multipoint maximum LOD score (MLS) analysis yielded significant evidence of linkage on 6q12 (MLS 3.30; empiric P=.024) and 17p11 (MLS 3.63; empiric P=.015), as well as suggestive evidence on 5p13 (MLS 2.55; empiric P=.091). In conjunction with the previously reported significant linkage on the basis of fine mapping 16p13 in the same sample as this report, the analyses presented here indicate that four chromosomal regions--5p13, 6q12, 16p13, and 17p11--are likely to harbor susceptibility genes for ADHD. The refinement of linkage within each of these regions lays the foundation for subsequent investigations using association methods to detect risk genes of moderate effect size.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Second-generation antipsychotic medications in children and adolescents.

OBJECTIVE: We reviewed available pediatric literature on second-generation antipsychotic medications to assess current evidence of efficacy and safety. METHOD: An English language MEDLINE search (1974-2003) was conducted using key words-atypical antipsychotics, children and adolescents, toxicity, clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole. Additional efficacy and safety data were obtained from drug manufacturers. RESULTS: We identified 176 reports, including 15 double-blind, controlled trials, 58 openlabel studies, 18 retrospective chart reviews, and 85 case series/reports. The majority of these studies (43%) were of risperidone. Evidence suggests that second-generation antipsychotics are efficacious in the treatment of psychosis, bipolar disorders, pervasive developmental disorders, and Tourette's Disorder, and are potentially useful in mental retardation, conduct disorder, and severe attention deficit hyperactivity disorder (ADHD). The most frequently reported side effects included cardiovascular effects, weight gain, sedation, sialorrhea, extrapyramidal signs, and hyperprolactinemia, although the relative frequencies of these untoward effects vary among medications. CONCLUSION: Although the evidence base for pediatric use of second-generation antipsychotics is expanding, the majority of available studies are anecdotal, or short-term, openlabel trials. Reports suggest that these compounds are effective for a variety of psychiatric disorders in children and adolescents, but additional double-blind, controlled studies are required to establish definitive efficacy. Although these medications appear to be well tolerated in short-term studies, long-term follow-up investigations and ongoing clinical monitoring are necessary to confirm their safety in this age group.

Adolescent↗