Showing papers by "James J. McGough published in 2009"

Estimating the size of treatment effects: moving beyond p values.

Abstract: Objective: To increase understanding of effect size calculations among clinicians who over-rely on interpretations of P values in their assessment of the medical literature. Design: We review five methods of calculating effect sizes: Cohen’s d (also known as the standardized mean difference)—used in studies that report efficacy in terms of a continuous measurement and calculated from two mean values and their standard deviations; relative risk—the ratio of patients responding to treatment divided by the ratio of patients responding to a different treatment (or placebo), which is particularly useful in prospective clinical trials to assess differences between treatments; odds ratio— used to interpret results of retrospective case-control studies and provide estimates of the risk of side effects by comparing the probability (odds) of an outcome occurring in the presence or absence of a specified condition; number needed to treat—the number of subjects one would expect to treat with agent A to have one more success (or one less failure) than if the same number were treated with agent B; and area under the curve (also known as the drug-placebo response curve)—a six-step process that can be used to assess the effects of medication on both worsening and improvement and the probability that a medication-treated subject will have a better outcome than a placebo-treated subject. Conclusion: Effect size statistics provide a better estimate of treatment effects than P values alone.

Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder: a placebo-controlled trial.

Abstract: Objective This study compared the efficacy of guanfacine extended release (GXR), a selective α 2A -adrenoceptor agonist, with placebo in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Method This double-blind, 9-week, dose-ranging, parallel-design, multicenter trial randomized 6- to 17-year-olds with ADHD to once-daily oral GXR in 1 -, 2-, 3-, and 4-mg doses or placebo. Primary outcome was change in total ADHD Rating Scale–IV score from baseline to endpoint. Secondary outcomes included changes in scores of hyperactive/impulsive and inattentive subscales; clinician and parent ratings; duration of clinical effect; and safety measures. Results Statistically significant reductions in ADHD Rating Scale-IV scores were observed from baseline to endpoint at all doses of GXR, with effect sizes ranging from 0.43 to 0.62. In subjects receiving GXR, mean heart rate and systolic and diastolic blood pressure decreased as the dose of GXR increased and then returned toward baseline during the dose-maintenance and dose-tapering phases of the trial. Most frequent treatment-emergent adverse events (≥ 5%) were somnolence, headache, fatigue, sedation, dizziness, irritability, upper abdominal pain, and nausea. Somnolence, sedation, and fatigue adverse events emerged within the first 2 weeks of dosing and generally resolved by study end. Conclusions Guanfacine extended-release was effective in reducing symptoms of ADHD. Adverse events were mild to moderate, did not interfere with improvements in attention, and rarely led to discontinuation.

Long-term safety and efficacy of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder.

Abstract: Objective: Short-term, controlled studies of extended-release guanfacine (GXR), a selective α2A-adrenoreceptor agonist, demonstrate efficacy in treating attention-deficit/hyperactivity disorder (ADHD) symptoms as monotherapy. This 2-year open-label study was conducted to further assess the long-term safety and efficacy of GXR. Methods: Study participants, aged 6–17 years with ADHD, had previously been exposed to GXR therapy alone or in combination with psychostimulants in one of two antecedent trials. In this study, doses were titrated to 1, 2, 3, or 4 mg/day of GXR alone or in combination with a psychostimulant. Safety and efficacy data collected at clinic visits over 24 months provided further evidence of the overall safety and efficacy of GXR for treating ADHD. Results: The majority of adverse events (AEs) were mild to moderate, and few patients discontinued the study because of an AE. Efficacy measures demonstrated significant improvement beginning in the first month and lasting through the e...

Mindfulness and attention deficit hyperactivity disorder.

Abstract: Attention deficit hyperactivity disorder (ADHD) is a disorder characterized by attentional difficulties. Mindfulness is a receptive attention to present experience. Both ADHD and mindfulness are associated with attention and personality. This study tests whether individuals with ADHD have lower mindfulness scores than controls and, if true, whether personality contributes to these differences. One hundred and five adults (half with ADHD) were assessed for mindfulness, using the Kentucky Inventory of Mindfulness Skills, and personality, using the Tridimensional Character Inventory. Individuals with ADHD report themselves as less mindful than non-ADHD controls and more novelty-seeking, less self-directed, and more self-transcendent. Mindfulness is negatively associated with ADHD and positively associated with self-directedness and self-transcendence. Analyses of subscales of mindfulness suggest that ADHD is associated most with the "Acting in Awareness" dimension, perhaps because of shared items reflecting attentional variability. The current findings support that a large portion of variability in trait mindfulness can be explained by ADHD status and personality traits of self-directedness and self-transcendence. It further suggests that interventions that increase mindfulness might improve symptoms of ADHD and increase self-directedness and/or self-transcendence.

A Candidate Gene Analysis of Methylphenidate Response in Attention-Deficit/Hyperactivity Disorder

Abstract: Objective This study examines the potential role of candidate genes in moderating treatment effects of methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD). Method Eighty-two subjects with ADHD aged 6 to 17 years participated in a prospective, double-blind, placebo-controlled, multiple-dose, crossover titration trial of immediate release MPH three times daily. The subjects were assessed on a variety of parent and clinician ratings and a laboratory math test. Data reduction based on principal components analysis identified statistically derived efficacy and side effect outcomes. Results Attention-deficit/hyperactivity disorder symptom response was predicted by polymorphisms at the serotonin transporter ( SLC6A4 ) intron 2 VNTR ( p = .01), with a suggested trend for catechol-O-methyltransferase ( COMT ) ( p = .04). Gene × dose interactions were noted on math test outcomes for the dopamine D4 receptor ( DRD4 ) promoter ( p = .008), DRD4 exon 3 VNTR ( p = .006), and SLC6A4 promoter insertion/deletion polymorphism ( 5HTTLPR ) ( p = .02). Irritability was predicted by COMT ( p = .02). Vegetative symptoms were predicted by 5HTTLPR ( p = .003). No significant effects were noted for the dopamine transporter ( SLC6A3 ) or synaptosomal-associated protein 25 ( SNAP25 ). Conclusions This article confirms and expands previous studies suggesting that genes moderate ADHD treatment response. The ADHD outcomes are not unitary but reflect both behavioral and learning domains that are likely influenced by different genes. Future research should emphasize candidate gene and genome-wide association studies in larger samples, symptom reduction as well as side effects outcomes, and responses over full therapeutic dose ranges to assess differences in both gene and gene × dose interactive effects.

Long-term effectiveness and safety of dexmethylphenidate extended-release capsules in adult ADHD.

Abstract: Objective: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. Method: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness outcomes included change from Week 5 on ADHD Rating Scale (ADHD-RS) and proportion of responders on Clinical Global Impressions—Improvement (CGI-I) scale. Results: 103 patients completed OLE, and effectiveness was evaluable in 102 patients. d-MPH-ER was well tolerated; the most common adverse events (>15%) were headache, insomnia, and decreased appetite. Mean improvements in ADHD-RS score were −10.2 for patients switched from placebo to d-MPH-ER (n = 20) and −8.4 for those maintained on d-MPH-ER (n = 82). Respective CGI-I responder rates were 95.0% and 95.1%. Conclusion: Once-daily d-MPH-ER 20 to 40 mg is safe and effective for long-term treatment of adult ADHD. (J. ...