Biomedical subjects

C Keith Conners

Publications and source records attributed to C Keith Conners.

16 recordsLinked to original sources

PubMed2005

Patterns and predictors of attention-deficit/hyperactivity disorder persistence into adulthood: results from the national comorbidity survey replication.

BACKGROUND: Despite growing interest in adult attention-deficit/hyperactivity disorder (ADHD), little is known about predictors of persistence of childhood cases into adulthood. METHODS: A retrospective assessment of childhood ADHD, childhood risk factors, and a screen for adult ADHD were included in a sample of 3197 18-44 year old respondents in the National Comorbidity Survey Replication (NCS-R). Blinded adult ADHD clinical reappraisal interviews were administered to a sub-sample of respondents. Multiple imputation (MI) was used to estimate adult persistence of childhood ADHD. Logistic regression was used to study retrospectively reported childhood predictors of persistence. Potential predictors included socio-demographics, childhood ADHD severity, childhood adversity, traumatic life experiences, and comorbid DSM-IV child-adolescent disorders (anxiety, mood, impulse-control, and substance disorders). RESULTS: Blinded clinical interviews classified 36.3% of respondents with retrospectively assessed childhood ADHD as meeting DSM-IV criteria for current ADHD. Childhood ADHD severity and childhood treatment significantly predicted persistence. Controlling for severity and excluding treatment, none of the other variables significantly predicted persistence even though they were significantly associated with childhood ADHD. CONCLUSIONS: No modifiable risk factors were found for adult persistence of ADHD. Further research, ideally based on prospective general population samples, is needed to search for modifiable determinants of adult persistence of ADHD.

Adolescent↗

PubMed2005

Peer-assessed outcomes in the multimodal treatment study of children with attention deficit hyperactivity disorder.

Peer-assessed outcomes were examined at the end of treatment (14 months after study entry) for 285 children (226 boys, 59 girls) with attention deficit hyperactivity disorder (ADHD) who were rated by their classmates (2,232 classmates total) using peer sociometric procedures. All children with ADHD were participants in the Multimodal Treatment Study of Children with ADHD (MTA). Treatment groups were compared using the orthogonal treatment contrasts that accounted for the largest amount of variance in prior MTA outcome analyses: Medication Management + Combined Treatment versus Behavior Therapy + Community Care; Medication Management versus Combined Treatment; Behavior Therapy versus Community Care. There was little evidence of superiority of any of the treatments for the peer-assessed outcomes studied, although the limited evidence that emerged favored treatments involving medication management. Post hoc analyses were used to examine whether any of the four treatment groups yielded normalized peer relationships relative to randomly selected-classmates. Results indicated that children from all groups remained significantly impaired in their peer relationships.

Attention Deficit Disorder with Hyperactivity↗

PubMed2004

Nine months of multicomponent behavioral treatment for ADHD and effectiveness of MTA fading procedures.

We examined 9-month data from the 14-month NIMH Multimodal Treatment Study of Children with ADHD (the MTA) as a further check on the relative effect of medication (MedMgt) and behavioral treatment (Beh) for attention-deficit/hyperactivity disorder (ADHD) while Beh was still being delivered at greater intensity than at 14-month endpoint, and conversely as a check on the efficacy of the MTA behavioral generalization/maintenance procedures. Intention-to-treat analysis at 9 months showed essentially the same results as at 14 months, after Beh had been completely faded; MedMgt and the combination (Comb) of medication and Beh were significantly superior to Beh and community care (CC) for ADHD and oppositional-defiant (ODD) symptoms, with mixed results for social skills and internalizing symptoms. All treatment-group differences examined as changes in slopes from 9 to 14 months were nonsignificant (we found general improvement for all groups). Slopes from baseline to 9 months correlated highly (r > .74, p < .0001) with slopes from baseline to 14 months for all groups. The time function from baseline to 14 months showed a significant linear, but not quadratic, trend for the main outcome measure (a composite of parent- and teacher-rated ADHD and ODD symptoms) for all groups. Findings suggest that in contrast to the hypothesized deterioration in the relative benefit of Beh between 9 and 14 months (after completion of fading), the MTA Beh generalization and maintenance procedures implemented through 9 months apparently yielded continuing improvement through 14 months, with preservation of the relative position of Beh compared to other treatment strategies.

Analysis of Variance↗

PubMed2004

A double-blind, placebo-controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention deficit hyperactivity disorder.

OBJECTIVES: d,l-threo-methylphenidate HCl (D,L-MPH) is the most common treatment of attention deficit hyperactivity disorder (ADHD). A previous report showed placebo-controlled efficacy for the purified d-isomer (dexmethylphenidate hydrochloride, d-MPH, Focalin) with a 2:1 potency compared to dl, and suggested a 6-hour duration of action. This study complements that report by studying the effect of placebo-controlled discontinuation and retesting the duration of action. METHODS: A 6-week, open-label titration of d-MPH (2.5-10 mg twice-a-day) was followed by a double-blind, placebo-controlled, 2-week withdrawal study of responders. RESULTS: In the open titration, 82% of the 89 enrolled patients achieved a Clinical Global Impression-Improvement (CGI-I) rating of much or very much improved. Only 5 patients discontinued for adverse events. Seventy-five patients continued into the placebo-controlled discontinuation. For the randomly assigned d-MPH (n=35) and placebo (n=40) groups, mean ages, respectively, were 10.1 +/- 2.9 and 9.9 +/- 2.7 years, 86% and 78% were male, and 70.6% and 80.0% took the ceiling dose of 10 mg twice-daily, respectively. Each group had 80% combined type ADHD and 20% inattentive type. By the end of the 2-week, placebo-masked withdrawal, significantly more placebo patients (24 of 39) than d-MPH continuers (6 of 35) relapsed (61.5% versus 17.1%, p=0.001). Compared to d-MPH continuers, placebo patients deteriorated significantly more in the 2-week period on teacher ratings of the 18 ADHD symptoms rated 0-3 (p=0.028), the 3 p.m. and 6 p.m. parent ADHD symptom ratings (p=0.0026 and p=0.0381, respectively), and clinic (2-3 p.m.) and home (6 p.m.) Math Tests (p=0.024 and p<0.0001, respectively). The 6 p.m. scores replicated the significant effect at 6 hours reported in the previous study. CONCLUSIONS: d-MPH is safe, tolerable, and effective, with a 6-hour duration of effect suggested by the significant difference from placebo at 6 hours on a double-blind discontinuation.

Adolescent↗

PubMed2004

A double-blind, placebo-controlled trial of dexmethylphenidate hydrochloride and d,l-threo-methylphenidate hydrochloride in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: To evaluate the efficacy and safety of dexmethylphenidate hydrochloride (d-MPH, Focalin) for the treatment of attention-deficit/hyperactivity disorder (ADHD) and to test an a priori hypothesis that d-MPH would have a longer duration of action than d,l-threo-methylphenidate (d,l-MPH). METHOD: This was a randomized, double-blind study conducted at 12 U.S. centers. One hundred thirty-two subjects received d-MPH (n=44), d,l-MPH (n=46), or placebo (n=42) twice daily for 4 weeks, with titration of the dose based on weekly clinic visits. The primary efficacy variable was change from baseline to last study visit on teacher-completed Swanson, Nolan, and Pelham Rating Scale (Teacher SNAP). Secondary efficacy measures included the change on parent-completed SNAP (Parent SNAP), Clinical Global Impressions Scale-Improvement (CGI-I) score, and Math Test performance. Assessments at home in late afternoon were included to test the hypothesis that d-MPH would have a longer duration of efficacy than d,l-MPH. Safety was assessed through monitoring occurrence and severity of adverse events and discontinuations related to them. RESULTS: Treatment with either d-MPH (p=.0004) or d,l-MPH (p=.0042) significantly improved Teacher SNAP ratings compared with placebo. The d-MPH group showed significant improvements compared with placebo on the afternoon Parent SNAP ratings (p=.0003) and scores on the Math Test (p=.0236) obtained late in the afternoon at 6:00 p.m. Sixty-seven percent of patients showed improvement on d-MPH and 49% on d,l-MPH based on CGI-I scores. Both d-MPH and d,l-MPH were well tolerated, no patient in the d-MPH group and only two patients each in the d,l-MPH and placebo groups discontinued the study. CONCLUSIONS: For the treatment of ADHD, an average titrated dose of 18.25 mg/day of d-MPH is as efficacious and safe as an average titrated dose of 32.14 mg/day of d,l-MPH. Both active treatments have large effect sizes. Thus, d-MPH and d,l-MPH appear to provide similar efficacy, and d-MPH may have longer duration of action after twice-daily dosing, but additional studies are needed to determine the statistical and clinical significance of this possibility.

Administration, Oral↗

PubMed2003

Relations between Continuous Performance Test performance measures and ADHD behaviors.

The Conners' Continuous Performance Test (CPT) is a neuropsychological task that has repeatedly been shown to differentiate ADHD from normal groups. Several variables may be derived from the Conners' CPT including errors of omission and commission, mean hit reaction time(RT), mean hit RT standard error, d', and beta. What each CPT parameter actually assesses has largely been based upon clinical assumptions and the face validity of each measure (e.g., omission errors measure inattention, commission errors measure impulsivity). This study attempts to examine relations between various CPT variables and phenotypic behaviors so as to better understand the various CPT variables. An epidemiological sample of 817 children was administered the Conners' CPT. Diagnostic interviews were conducted with parents to determine ADHD symptom profiles for all children. Children diagnosed with ADHD had more variable RTs, made more errors of commission and omission, and demonstrated poorer perceptual sensitivity than nondiagnosed children. Regarding specific symptoms, generalized estimating equations (GEE) and ANCOVAs were conducted to determine specific relationships between the 18 DSM-IV ADHD symptoms and 6 CPT parameters. CPT performance measures demonstrated significant relationships to ADHD symptoms but did not demonstrate symptom domain specificity according to a priori assumptions. Overall performance on the two signal detection measures, d' and beta, was highly related to all ADHD symptoms across symptom domains. Further, increased variability in RTs over time was related to most ADHD symptoms. Finally, it appears that at least 1 CPT variable, mean hit RT, is minimally related to ADHD symptoms as a whole, but does demonstrate some specificity in its link with symptoms of hyperactivity.

Algorithms↗

PubMed2003

Continuous performance test performance in a normative epidemiological sample.

A 14-min continuous performance test (CPT) requiring a high rate of responding was administered to a probability-weighted random sample of 816 9-17-year-old children drawn from a population of 17,117 children in an ongoing epidemiological and longitudinal study in Western North Carolina. Systematic main effects of improved performance with older age were found in this age range for all variables, including reaction time (RT), RT standard error, errors of omission, errors of commission, and signal detection parameters (d' and beta). Significant gender main effects included more impulsive errors, less variability, and faster RT by males, with no interactions between age and gender. There were no main effects of ethnicity or interactions of ethnicity with age and/or gender. Large main effects of interstimulus interval (ISI; 1, 2, or 4-s intervals) and time block were present for most CPT performance measures. The normative data from the CPT should provide a useful framework for interpreting similar data in future studies of child and adolescent psychopathology.

Adolescent↗

PubMed2003

Which treatment for whom for ADHD? Moderators of treatment response in the MTA.

Using receiver operating characteristics, the authors examined outcome predictors (variables associated with outcome regardless of treatment) and moderators (variables identifying subgroups with differential treatment effectiveness) in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD; MTA). Treatment response was determined using parent- and teacher-reported ADHD and oppositional defiant symptoms, with levels near or within the normal range indicating excellent response. Among 9 baseline child and family characteristics, none predicted but 3 moderated treatment response. In medication management and combined treatments, parental depressive symptoms and severity of child ADHD were associated with decreased rates of excellent response; when these 2 characteristics were present, below-average child IQ was an additional moderator. No predictors or moderators emerged for behavioral and community comparison treatments. The authors discuss conceptual and clinical implications of research on treatment moderators.

Attention Deficit Disorder with Hyperactivity↗

PubMed2003

Effects of ethnicity on treatment attendance, stimulant response/dose, and 14-month outcome in ADHD.

From the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder--a randomized clinical trial of 579 children ages 7-9 years receiving 14 months of medication management, behavioral treatment, combination, or community care--the authors matched each African American and Latino participant with randomly selected Caucasian participants of same sex, treatment group, and site. Although Caucasian children were significantly less symptomatic than African American and Latino children on some ratings, response to treatment did not differ significantly by ethnicity after controlling for public assistance. Ethnic minority families cooperated with and benefited significantly from combination (multimodal) treatment (d = 0.36, compared with medication). This incremental gain withstood statistical control for mother's education, single-parent status, and public assistance. Treatment for lower socioeconomic status minority children, especially if comorbid, should combine medication and behavioral treatment.

Attention Deficit Disorder with Hyperactivity↗

PubMed2003

ADHD treatment with once-daily OROS methylphenidate: interim 12-month results from a long-term open-label study.

OBJECTIVE: Few treatment studies of attention-deficit/hyperactivity disorder (ADHD) extend beyond a few months. This article reports an interim analysis of a 24-month study evaluating the 12-month tolerability and effectiveness of a once-daily OROS formulation of methylphenidate (OROS MPH) in children with ADHD. METHOD: Children, aged 6-13 years, with ADHD who participated in previous controlled studies and were MPH responders, received once-daily OROS MPH in this multicenter, open-label, nonrandomized study. Effectiveness was evaluated monthly by parents/caregivers and schoolteachers using validated rating scales (e.g., IOWA Conners). Safety and adverse events assessments involved objective (e.g., vital signs, growth) and subjective (sleep quality, tics) reporting. RESULTS: Seventy-one percent of subjects (289/407) completed 12 months' treatment. Effectiveness was maintained throughout 12 months as demonstrated by stable IOWA Conners ratings and sustained improvements in peer interaction and Global Assessment Scale scores. OROS MPH was well tolerated, with adverse events similar to those expected with short-acting stimulant medication. OROS MPH had minimal impact on sleep quality and tics. There were no clinically meaningful changes in blood pressure, pulse, or height. The apparent absence of meaningful changes is tempered by the fact that children were MPH responders and were medicated at baseline, most for extended periods prior to enrollment. CONCLUSION: In this open-label study, once-daily OROS MPH treatment appears to be well tolerated and effectiveness was maintained for up to 12 months in these children with ADHD.

Adolescent↗

PubMed2002

Observed classroom behavior of children with ADHD: relationship to gender and comorbidity.

Examined hypothesized gender and comorbidity differences in the observed classroom behavior of children with attention deficit hyperactivity disorder (ADHD). The behavior of 403 boys and 99 girls with ADHD, ages 7-10, was compared (a) to observed, sex-specific classroom behavior norms, (b) by sex, and (c) by comorbid subgroups. Boys and girls with ADHD deviated significantly from classroom norms on 15/16 and 13/16 categories, respectively. Compared to comparison girls, girls with ADHD had relatively high rates of verbal aggression to children. Boys with ADHD engaged in more rule-breaking and externalizing behaviors than did girls with ADHD, but the sexes did not differ on more "neutral," unobtrusive behaviors. The sex differences are consistent with notions of why girls with ADHD are identified and referred later than boys. Contrary to hypothesis, the presence of comorbid anxiety disorder (ANX) was not associated with behavioral suppression; yet, as hypothesized, children with a comorbid disruptive behavior disorder (DBD) had higher rates of rule-breaking, and impulsive and aggressive behavior, than did children with ADHD alone and those with ADHD+ANX. Elevated rates of ADHD behaviors were also observed in children with comorbid DBD, indicating that these behaviors are truly present and suggesting that reports of higher ADHD ratings in this subgroup are not simply a consequence of negative halo effects and rater biases.

Anxiety Disorders↗

PubMed2002

Socioeconomic status as a moderator of ADHD treatment outcomes.

OBJECTIVE: To explore whether socioeconomic status (SES) variables moderate treatment response of attention-deficit/hyperactivity disorder (ADHD) to medication management (MedMgt), behavioral treatment (Beh), combined intervention (Comb), and routine community care (CC). METHOD: The MTA Cooperative Group's intent-to-treat (ITT) analyses were repeated, covarying for composite Hollingshead SES, education, occupation, income, and marital status. RESULTS: Individual SES variables were more informative than the composite Hollingshead Index. Treatment response of children from less educated households paralleled ITT outcomes: no significant difference was found between Comb and MedMgt (both better than Beh and CC) for core ADHD symptoms. However, children from more educated families showed superior reduction of ADHD symptoms with Comb. For oppositional-aggressive symptoms, children from blue-collar, lower SES households benefited most from Comb, whereas those from white-collar, higher SES homes generally showed no differential treatment response. Household income and marital status failed to influence outcomes. Controlling for treatment attendance attenuated the moderating effects of the SES variables only for MedMgt. CONCLUSIONS: Investigators are encouraged to use independent SES variables for maximal explanation of SES effects. Clinicians should prioritize target symptoms and consider the mediating role of treatment adherence when determining an ADHD patient's optimal intervention plan.

Attention Deficit Disorder with Hyperactivity↗

PubMed2002

Emergency/Adjunct services and attrition prevention for randomized clinical trials in children: the MTA manual-based solution.

Treatment studies in child and adolescent psychiatry are increasingly characterized by long-term, multisite, randomized clinical trials (RCTs). During the course of these RCTs it is common for clinical exigencies to emerge that require rapid, direct intervention. The challenge is to provide clinically appropriate responses that do not contaminate the delivery, distinctness, and interpretation of the treatments under investigation. In multisite studies, the problem is compounded by the need to minimize cross-site differences in the delivery of adjunct treatments. Such minimization requires fully operationalized and manual-based procedures for clinically mandated intervention. The NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (ADHD)--"the MTA"--is a long-term multisite collaborative study in which children with ADHD were randomly assigned to either medication management, behavioral treatment, the combination, or community-comparison assessment and referral. In designing its study, the MTA developed a manual-based set of procedures (the MTA Adjunct Services and Attrition Prevention [ASAP] Manual) for situations not covered by the protocol treatments. The majority of cases requiring adjunct services fell into two major categories: (1) crisis/emergent situations and (2) imminent risk of attrition. This report describes the ASAP guidelines for dealing with cases that required adjunct services that the MTA Steering Committee adopted before initiating the trial. Although the manual-based guidelines are especially applicable to multisite RCTs, many of the procedures in the ASAP Manual can apply to any treatment study in children.

Attention Deficit Disorder with Hyperactivity↗

PubMed2002

GW320659 for the treatment of attention-deficit/hyperactivity disorder in children.

OBJECTIVE: To assess the safety, tolerability, and efficacy of GW320659, a chemically novel inhibitor of norepinephrine and dopamine reuptake, in pediatric attention-deficit/hyperactivity disorder (ADHD). METHOD: This was a multicenter, open-label, dose-titration study of seven daily dose levels of GW320659: 1.25, 2.5, 5, 7.5,10,12.5, and 15 mg. Treatment began with the lowest dose of GW320659 and increased weekly until subjects (mean age 9.1 years) achieved a maximum acceptable dose. Subjects remained at their maximum acceptable dose for a 4-week treatment period. The key efficacy end-point was clinical response (Clinical Global Impressions of Improvement score of 1 or 2 and an improvement of 5 or more points on at least one of the Conners Parent or Teacher Rating Scales Tscore). Other end-points included assessments of safety and of quality of life using the Child Health Questionnaire Parent Form 28 (CHQ-PF28). RESULTS: Fifty-one subjects entered the titration phase and 46 subjects completed the study. During the treatment phase, these 46 subjects received a mean dose of 14.2 mg/day and the maximum exposure to GW320659 was 11 weeks. At the end of the treatment period, 76% of subjects showed improvement with GW320659 and there were significant improvements in 7 of the 12 subscales of the CHQ-PF28 compared with baseline (p < .05). Adverse events were generally mild; only five subjects required downward titration because of adverse events (three psychiatric, one neurological and urological, one cardiovascular), and no subject withdrew because of adverse events. CONCLUSIONS: GW320659 may have clinically relevant efficacy in pediatric ADHD and was well tolerated in this short-term initial study in children.

Adrenergic Uptake Inhibitors↗

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↗

PubMed1997

Asymmetrical hemispheric control of visual-spatial attention in adults with attention deficit hyperactivity disorder.

As neuropsychological mechanisms for attention have been hypothesized to be located in the right hemisphere of the brain, several investigators have begun to conceptualize attention deficit hyperactivity disorder (ADHD)-related attentional deficits as involving right-hemispheric abnormalities. The authors evaluated and compared adult patients diagnosed with ADHD with a non-ADHD group of patients using a chronometric visual-spatial attention task that is sensitive to hemispheric differences in efficiency of information processing. Reaction times across different cuing conditions, cue-target delays, and visual fields were assessed. When participants' attention was misdirected with cues in the right visual field and attention had to be switched to a target on the left visual field, there was a longer delay among ADHD adults than non-ADHD adults, specifically when the interval between the cue and target was 800 ms as compared with 100 ms. This specific pattern of dysfunction was interpreted as a difficulty with maintaining attention possibly associated with anterior attention mechanisms in the right hemisphere.

Adolescent↗