Participants of the Multimodal Treatment Study of Children with Attention Deficit and Hyperactivity Disorder (ADHD) eight years earlier do not differ significantly in repeated measures or newly ...analyzed variables that include school grades and psychiatric hospitalization. The treatment of childhood ADHD does not predict functioning six to eight years later.
Brain dopamine dysfunction in attention deficit/hyperactivity disorder (ADHD) could explain why stimulant medications, which increase dopamine signaling, are therapeutically beneficial. However while ...the acute increases in dopamine induced by stimulant medications have been associated with symptom improvement in ADHD the chronic effects have not been investigated.
We used positron emission tomography and (11)Ccocaine (dopamine transporter radioligand) to measure dopamine transporter availability in the brains of 18 never-medicated adult ADHD subjects prior to and after 12 months of treatment with methylphenidate and in 11 controls who were also scanned twice at 12 months interval but without stimulant medication. Dopamine transporter availability was quantified as non-displaceable binding potential using a kinetic model for reversible ligands.
Twelve months of methylphenidate treatment increased striatal dopamine transporter availability in ADHD (caudate, putamen and ventral striatum: +24%, p<0.01); whereas there were no changes in control subjects retested at 12-month interval. Comparisons between controls and ADHD participants revealed no significant difference in dopamine transporter availability prior to treatment but showed higher dopamine transporter availability in ADHD participants than control after long-term treatment (caudate: p<0.007; putamen: p<0.005).
Upregulation of dopamine transporter availability during long-term treatment with methylphenidate may decrease treatment efficacy and exacerbate symptoms while not under the effects of the medication. Our findings also suggest that the discrepancies in the literature regarding dopamine transporter availability in ADHD participants (some studies reporting increases, other no changes and other decreases) may reflect, in part, differences in treatment histories.
Objective: To determine long-term effects on substance use and substance use disorder (SUD), up to 8 years after childhood enrollment, of the randomly assigned 14-month treatments in the multisite ...Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (MTA; n = 436); to test whether medication at follow-up, cumulative psychostimulant treatment over time, or both relate to substance use/SUD; and to compare substance use/SUD in the ADHD sample to the non-ADHD childhood classmate comparison group (n = 261). Method: Mixed-effects regression models with planned contrasts were used for all tests except the important cumulative stimulant treatment question, for which propensity score matching analysis was used. Results: The originally randomized treatment groups did not differ significantly on substance use/SUD by the 8-year follow-up or earlier (mean age = 17 years). Neither medication at follow-up (mostly stimulants) nor cumulative stimulant treatment was associated with adolescent substance use/SUD. Substance use at all time points, including use of two or more substances and SUD, were each greater in the ADHD than in the non-ADHD samples, regardless of sex. Conclusions: Medication for ADHD did not protect from, or contribute to, visible risk of substance use or SUD by adolescence, whether analyzed as randomized treatment assignment in childhood, as medication at follow-up, or as cumulative stimulant treatment over an 8-year follow-up from childhood. These results suggest the need to identify alternative or adjunctive adolescent-focused approaches to substance abuse prevention and treatment for boys and girls with ADHD, especially given their increased risk for use and abuse of multiple substances that is not improved with stimulant medication. Clinical trial registration information--Multimodal Treatment Study of Children With Attention Deficit and Hyperactivity Disorder (MTA); http://clinical trials.gov/; NCT00000388. (Contains 2 figures and 1 table.)
Duration of efficacy and safety of lisdexamfetamine dimesylate (LDX) was assessed in adults (18-55 years) with attention-deficit/hyperactivity disorder (ADHD) using the simulated adult workplace ...environment.
After open-label dose optimization (4-week) with LDX, 30-70 mg/d, subjects entered a 2-week randomized, double-blind, placebo-controlled crossover phase. Efficacy assessments included the Permanent Product Measure of Performance (PERMP) total score (attempted+correct) measured predose and from 2 to 14 hours postdose, averaged across postdose sessions (primary) and at each time point vs placebo (secondary), and ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts at baseline and crossover visits. Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, and electrocardiograms.
Of 127 randomized subjects, 105 were in the intention-to-treat population and 103 completed the study. While receiving LDX vs placebo, adults had greater improvement (P < .0001) in average PERMP total scores as measured by difference in least squares (LS) mean (95% CI): 23.4 (15.6, 31.2). Absolute (P <or= .0017 for each time point) and change from predose (P < .001 for each time point) PERMP total scores were greater at all postdose time points from 2 to 14 h for adults while receiving LDX vs placebo. LDX demonstrated efficacy vs placebo (P < .0001) by the difference in LS mean (95% CI) for ADHD-RS-IV total scores: -11.5 (-14.2, -8.9). TEAEs (>or=10%) during dose optimization were decreased appetite, dry mouth, headache, and insomnia; no TEAEs >or=5% were reported during crossover phase for adults receiving LDX.
LDX significantly improved PERMP scores vs placebo and maintained improvement throughout the day from the first (2 hours) to last (14 hours) postdose time point vs placebo in adults with ADHD.
ClinicalTrials.gov Identifier: NCT00697515. Safety and Efficacy Workplace Environment Study of Lisdexamfetamine Dimesylate (LDX) in Adults With Attention-Deficit Hyperactivity Disorder (ADHD) http://www.clinicaltrials.gov/ct2/show/NCT00697515?term=NCT00697515&rank=1.
3-Year Follow-up of the NIMH MTA Study Jensen, Peter S; Arnold, L. Eugene; Swanson, James M ...
Journal of the American Academy of Child and Adolescent Psychiatry,
08/2007, Letnik:
46, Številka:
8
Journal Article
Recenzirano
Objective: In the intent-to-treat analysis of the Multimodal Treatment Study of Children With ADHD (MTA), the effects of medication management (MedMgt), behavior therapy (Beh), their combination ...(Comb), and usual community care (CC) differed at 14 and 24 months due to superiority of treatments that used the MTA medication algorithm (Comb+MedMgt) over those that did not (Beh+CC). This report examines 36-month outcomes, 2 years after treatment by the study ended. Method: For primary outcome measures (attention-deficit/hyperactivity disorder ADHD and oppositional defiant disorder ODD symptoms, social skills, reading scores, impairment, and diagnostic status), mixed-effects regression models and orthogonal contrasts examined 36-month outcomes. Results: At 3 years, 485 of the original 579 subjects (83.8%) participated in the follow-up, now at ages 10 to 13 years, (mean 11.9 years). In contrast to the significant advantage of MedMgt+Comb over Beh+CC for ADHD symptoms at 14 and 24 months, treatment groups did not differ significantly on any measure at 36 months. The percentage of children taking medication greater than 50% of the time changed between 14 and 36 months across the initial treatment groups: Beh significantly increased (14% to 45%), MedMed+Comb significantly decreased (91% to 71%), and CC remained constant (60%-62%). Regardless of their treatment use changes, all of the groups showed symptom improvement over baseline. Notably, initial symptom severity, sex (male), comorbidity, public assistance, and parental psychopathology (ADHD) did not moderate children's 36-month treatment responses, but these factors predicted worse outcomes over 36 months, regardless of original treatment assignment. Conclusions: By 36 months, the earlier advantage of having had 14 months of the medication algorithm was no longer apparent, possibly due to age-related decline in ADHD symptoms, changes in medication management intensity, starting or stopping medications altogether, or other factors not yet evaluated. (Contains 2 tables and 4 figures.)
Objective: To evaluate the hypothesis of stimulant medication effect on physical growth in the follow-up phase of the Multimodal Treatment Study of Children With ADHD. Method: Naturalistic subgroups ...were established based on patterns of treatment with stimulant medication at baseline, 14-, 24-, and 36-month assessments: not medicated (n = 65), newly medicated (n = 88), consistently medicated (n = 70), and inconsistently medicated (n = 147). Analysis of variance was used to evaluate effects of subgroup and assessment time on measures of relative size (z scores) obtained from growth norms. Results: The subgroup x assessment time interaction was significant for z height (p less than 0.005) and z weight (p less than 0.0001), due primarily to divergence of the newly medicated and the not medicated subgroups. These initially stimulant-naive subgroups had z scores significantly greater than 0 at baseline. The newly medicated subgroup showed decreases in relative size that reached asymptotes by the 36-month assessment, when this group showed average growth of 2.0 cm and 2.7 kg less than the not medicated subgroup, which showed slight increases in relative size. Conclusions: Stimulant-naive school-age children with Combined type attention-deficit/hyperactivity disorder were, as a group, larger than expected from norms before treatment but show stimulant-related decreases in growth rates after initiation of treatment, which appeared to reach asymptotes within 3 years without evidence of growth rebound. (Contains 3 tables and 2 figures.)
Smith and Farah (2011)
presented a scholarly review of critical areas related to their intriguing title "Are Prescription Stimulants 'Smart Pills'?" We contend that they accomplished the main goal of ...the article, to get the facts straight about possible cognitive enhancement via the nonmedical use of stimulant drugs by individuals without a diagnosis of attention-deficit/hyperactivity disorder (ADHD). At the same time, they justified their main conclusions that (a) individuals are seeking and engaging in nonmedical use of stimulant drugs with the expectations of cognitive enhancement despite uncertainty whether such expectations are valid and (b) on some tasks, there are small average benefits of nonmedical use, but the overall pattern is not clear (e.g., small beneficial effects across most individuals or large beneficial effects only in a few individuals, both of which result in small average effects). We offer comments in 3 areas to amplify key topics mentioned but not emphasized by Smith and Farah: (a) characterization of the cognitive effects of medical use of stimulants to contrast with the cognitive effects of nonmedical use; (b) justification of medical use of stimulants by placement on a normally distributed dimension of behavior rather than categorical diagnosis of ADHD, which varies widely across countries; and (c) evaluation of the potential risks of nonmedical use to individuals and to society (e.g., the likelihood of addiction to stimulant drugs in a small minority of the population) rather than just the potential benefits of cognitive enhancement.
Abstract The aim of the study was to examine functional brain activity in response to unpleasant images in individuals with the 7-repeat (7R) allele compared to individuals with the 4-repeat (4R) ...allele of the dopamine receptor D4 ( DRD4 ) gene (VNTR in exon 3). Based on the response ready hypothesis, individuals with the DRD4 -4R/7R genotype were expected to show greater functional brain activity in response to unpleasant compared to neutral stimuli in specific regions of the frontal, temporal, parietal and limbic lobes, which form the networks involved in attentional, emotional, and preparatory responses. Functional Magnetic Resonance Imaging activity was studied in 26 young adults (13 with the DRD4 -4R/7R genotype and 13 with the DRD4 -4R/4R genotype). Participants were asked to look at and subjectively rate unpleasant and neutral images. Results showed increased brain activity in response to unpleasant images compared to neutral images in the right temporal lobe in participants with the DRD4 -4R/7R genotype versus participants with the DRD4 -4R/4R genotype. The increase in right temporal lobe activity in individuals with DRD4 -4R/7R suggests greater involvement in processing negative emotional stimuli. Intriguingly, no differences were found between the two genotypes in the subjective ratings of the images. The findings corroborate the response ready hypothesis, which suggests that individuals with the 7R allele are more responsive to negative emotional stimuli compared to individuals with the 4R allele of the DRD4 gene.
Recent results from the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder (ADHD; MTA) have demonstrated impairments in several functioning domains in adults with childhood ADHD. ...The childhood predictors of these adult functional outcomes are not adequately understood. The objective of the present study was to determine the effects of childhood demographic, clinical, and family factors on adult functional outcomes in individuals with and without childhood ADHD from the MTA cohort.
Regressions were used to determine associations of childhood factors (age range 7-10 years) of family income, IQ, comorbidity (internalizing, externalizing, and total number of non-ADHD diagnoses), parenting styles, parental education, number of household members, parental marital problems, parent-child relationships, and ADHD symptom severity with adult outcomes (mean age 25 years) of occupational functioning, educational attainment, emotional functioning, sexual behavior, and justice involvement in participants with (n = 579) and without (n = 258) ADHD.
Predictors of adult functional outcomes in ADHD included clinical factors such as baseline ADHD severity, IQ, and comorbidity; demographic factors such as family income, number of household members and parental education; and family factors such as parental monitoring and parental marital problems. Predictors of adult outcomes were generally comparable for children with and without ADHD.
Childhood ADHD symptoms, IQ, and household income levels are important predictors of adult functional outcomes. Management of these areas early on, through timely treatments for ADHD symptoms, and providing additional support to children with lower IQ and from households with low incomes, could assist in improving adult functioning.
Introduction The objectives of this research were to assess skeletal and dental changes in patients with Class II malocclusion treated with the edgewise crowned Herbst appliance in the early mixed ...dentition and to measure the stability of treatment after a second phase of fixed appliance therapy. Methods Twenty-two patients (ages, 8.4 ± 1.0 years) with Class II Division 1 malocclusion treated consecutively with the edgewise crowned Herbst appliance in the early mixed dentition were studied. Lateral cephalograms were taken before Herbst treatment, immediately after Herbst treatment, and after a second phase of fixed appliance therapy. The results were compared with a control group of untreated Class II subjects selected from the Bolton-Brush study, matched by age, sex, and craniofacial morphology. A total of 37 sagittal, vertical, and angular cephalometric variables were evaluated. Changes in overjet and molar relationship were calculated. Changes due to growth were subtracted to obtain the net changes due to treatment. The data were analyzed by using analysis of variance (ANOVA) and the t tests. Results Overcorrection with the Herbst appliance resulted in an average reduction in overjet of 7.0 mm and a change in molar relationship of 6.6 mm. Several factors contributed to the change in overjet: restraint of the forward movement of the maxilla (0.4 mm), forward movement of the mandible (2.0 mm), backward movement of the maxillary incisors (3.7 mm), and forward movement of the mandibular incisors (0.9 mm). Skeletal changes together with a 3.1-mm backward movement of the maxillary molars and a 1.1-mm forward movement of the mandibular molars contributed to the changes in molar relationship. After the second phase of fixed appliance therapy, the change in overjet was reduced to 2.8 mm. Most of the remaining overjet corrections were contributed by the restraint of maxillary growth (2.8 mm). The mandible moved posteriorly by 1.6 mm, and the mandibular incisors moved forward by 0.2 mm. Change in molar relationship was reduced to 2.2 mm. The maxillary molars moved backward by 0.2 mm, and the mandibular molars moved forward by 0.8 mm. Conclusions Overcorrection of Class II malocclusion with the edgewise crowned Herbst appliance in the early mixed dentition resulted in a significant reduction in overjet and correction of the molar relationship. A portion of the correction was maintained after a second phase of fixed appliance therapy because of the continuous restraint of maxillary growth and the dentoalveolar adaptations.
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