Background: While studies have increasingly investigated deficits in reaction time (RT) and RT variability in children with attention deficit/hyperactivity disorder (ADHD), few studies have examined ...the effects of stimulant medication on these important neuropsychological outcome measures.
Methods: 316 children who participated in the Multimodal Treatment Study of Children with ADHD (MTA) completed the Conners’ Continuous Performance Test (CPT) at the 24‐month assessment point. Outcome measures included standard CPT outcomes (e.g., errors of commission, mean hit reaction time (RT)) and RT indicators derived from an Ex‐Gaussian distributional model (i.e., mu, sigma, and tau).
Results: Analyses revealed significant effects of medication across all neuropsychological outcome measures. Results on the Ex‐Gaussian outcome measures revealed that stimulant medication slows RT and reduces RT variability.
Conclusions: This demonstrates the importance of including analytic strategies that can accurately model the actual distributional pattern, including the positive skew. Further, the results of the study relate to several theoretical models of ADHD.
In general, recommendations for the
DSM-V
and future diagnoses of psychiatric disorders include a dimensional approach to complement the standard categorical approach. For the assessment of ...attention-deficit/hyperactivity disorder (ADHD), dimensional approaches to supplement the rigid categorical approach of the
DSM-IV
abound. Historically, dimensions based on severity of symptoms of ADHD and severity of general psychopathology have been used. General dimensional approaches described by a workgroup organized by the American Psychiatric Association are reviewed to provide background and context for a discussion of old and new dimensional approaches to complement future categorical diagnosis of ADHD in the
DSM-V
.
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent chronic condition that affects people of all ages, including young children, school-aged children, adolescents, and adults. Symptoms can ...be noted as early as preschool age, tend to progress into functional impairment and behavioral problems in later childhood, and typically persist into adulthood. Contrary to previous belief, the disorder does not resolve with puberty for the majority of children; rather, the symptoms are manifested differently throughout the lifecycle. Presentation in adults is heavily biased toward inattentive symptoms, which are less likely to draw notice than hyperactive or impulsive symptoms and may contribute to the underrecognition of ADHD in this patient population. Diagnosis is particularly difficult due in large part to the pronounced comorbidity of psychiatric disorders in this patient population. Identification may be even more difficult in adults than children as the diagnostic criteria are not as clear, adults have difficulty remembering symptoms prior to 7 years of age, and there is a high prevalence of comorbid psychiatric disorders in adults. Early identification and treatment of symptoms of ADHD in preschool-age children is essential to effective long-term management of the disorder. Both medication and behavioral treatments appear to alleviate the symptoms of ADHD, and evidence suggests that discontinuation of treatment leads to the reemergence of the condition. Efforts are currently continuing toward understanding the genetic underpinnings of ADHD. This expert review supplement will address the prevalence, comorbidity, treatment issues, and special considerations surrounding ADHD management throughout each stage of the lifecycle beginning with ADHD in preschool-aged children, continuing with school-aged children and adolescents, and ending with adulthood.
Background
The Multimodal Treatment Study (MTA) began as a 14‐month randomized clinical trial of behavioral and pharmacological treatments of 579 children (7–10 years of age) diagnosed with ...attention‐deficit/hyperactivity disorder (ADHD)‐combined type. It transitioned into an observational long‐term follow‐up of 515 cases consented for continuation and 289 classmates (258 without ADHD) added as a local normative comparison group (LNCG), with assessments 2–16 years after baseline.
Methods
Primary (symptom severity) and secondary (adult height) outcomes in adulthood were specified. Treatment was monitored to age 18, and naturalistic subgroups were formed based on three patterns of long‐term use of stimulant medication (Consistent, Inconsistent, and Negligible). For the follow‐up, hypothesis‐generating analyses were performed on outcomes in early adulthood (at 25 years of age). Planned comparisons were used to estimate ADHD‐LNCG differences reflecting persistence of symptoms and naturalistic subgroup differences reflecting benefit (symptom reduction) and cost (height suppression) associated with extended use of medication.
Results
For ratings of symptom severity, the ADHD‐LNCG comparison was statistically significant for the parent/self‐report average (0.51 ± 0.04, p < .0001, d = 1.11), documenting symptom persistence, and for the parent/self‐report difference (0.21 ± 0.04, p < .0001, d = .60), documenting source discrepancy, but the comparisons of naturalistic subgroups reflecting medication effects were not significant. For adult height, the ADHD group was 1.29 ± 0.55 cm shorter than the LNCG (p < .01, d = .21), and the comparisons of the naturalistic subgroups were significant: the treated group with the Consistent or Inconsistent pattern was 2.55 ± 0.73 cm shorter than the subgroup with the Negligible pattern (p < .0005, d = .42), and within the treated group, the subgroup with the Consistent pattern was 2.36 ± 1.13 cm shorter than the subgroup with the Inconsistent pattern (p < .04, d = .38).
Conclusions
In the MTA follow‐up into adulthood, the ADHD group showed symptom persistence compared to local norms from the LNCG. Within naturalistic subgroups of ADHD cases, extended use of medication was associated with suppression of adult height but not with reduction of symptom severity.
Read the Commentary on this article at doi: 10.1111/jcpp.12758
Objective
Longitudinal studies of children diagnosed with ADHD report widely ranging ADHD persistence rates in adulthood (5–75%). This study documents how information source (parent vs. self‐report), ...method (rating scale vs. interview), and symptom threshold (DSM vs. norm‐based) influence reported ADHD persistence rates in adulthood.
Method
Five hundred seventy‐nine children were diagnosed with DSM‐IV ADHD‐Combined Type at baseline (ages 7.0–9.9 years) 289 classmates served as a local normative comparison group (LNCG), 476 and 241 of whom respectively were evaluated in adulthood (Mean Age = 24.7). Parent and self‐reports of symptoms and impairment on rating scales and structured interviews were used to investigate ADHD persistence in adulthood.
Results
Persistence rates were higher when using parent rather than self‐reports, structured interviews rather than rating scales (for self‐report but not parent report), and a norm‐based (NB) threshold of 4 symptoms rather than DSM criteria. Receiver‐Operating Characteristics (ROC) analyses revealed that sensitivity and specificity were optimized by combining parent and self‐reports on a rating scale and applying a NB threshold.
Conclusion
The interview format optimizes young adult self‐reporting when parent reports are not available. However, the combination of parent and self‐reports from rating scales, using an ‘or’ rule and a NB threshold optimized the balance between sensitivity and specificity. With this definition, 60% of the ADHD group demonstrated symptom persistence and 41% met both symptom and impairment criteria in adulthood.
Read the Commentary on this article at doi: 10.1111/jcpp.12758
Podcast link
Adolescents and young adults without childhood attention deficit hyperactivity disorder (ADHD) often present to clinics seeking stimulant medication for late-onset ADHD symptoms. Recent birth-cohort ...studies support the notion of late-onset ADHD, but these investigations are limited by relying on screening instruments to assess ADHD, not considering alternative causes of symptoms, or failing to obtain complete psychiatric histories. The authors address these limitations by examining psychiatric assessments administered longitudinally to the local normative comparison group of the Multimodal Treatment Study of ADHD.
Individuals without childhood ADHD (N=239) were administered eight assessments from comparison baseline (mean age=9.89 years) to young adulthood (mean age=24.40 years). Diagnostic procedures utilized parent, teacher, and self-reports of ADHD symptoms, impairment, substance use, and other mental disorders, with consideration of symptom context and timing.
Approximately 95% of individuals who initially screened positive on symptom checklists were excluded from late-onset ADHD diagnosis. Among individuals with impairing late-onset ADHD symptoms, the most common reason for diagnostic exclusion was symptoms or impairment occurring exclusively in the context of heavy substance use. Most late-onset cases displayed onset in adolescence and an adolescence-limited presentation. There was no evidence for adult-onset ADHD independent of a complex psychiatric history.
Individuals seeking treatment for late-onset ADHD may be valid cases; however, more commonly, symptoms represent nonimpairing cognitive fluctuations, a comorbid disorder, or the cognitive effects of substance use. False positive late-onset ADHD cases are common without careful assessment. Clinicians should carefully assess impairment, psychiatric history, and substance use before treating potential late-onset cases.
Objectives: The objective of this paper was to evaluate the efficacy, duration of effect, and tolerability of SHP465 mixed amphetamine salts (MAS) extended-release versus placebo and ...immediate-release MAS (MAS IR) in adults with attention-deficit/hyperactivity disorder (ADHD).
Methods: Adults with ADHD Rating Scale, Version IV (ADHD-RS-IV) scores ≥24 were randomized to SHP465 MAS (50 or 75 mg), placebo, or 25 mg MAS IR in a double-blind, three-period, crossover study using a simulated adult workplace environment. On the final day of each 7-day treatment period, efficacy was assessed for 16 h postdose. Primary efficacy analyses for Permanent Product Measure of Performance (PERMP) total score averaged across all postdose assessments and each postdose time point were conducted in the intent-to-treat population using a mixed linear model. Secondary end-points included PERMP problems attempted and answered correctly and ADHD-RS-IV scores based on clinician ratings of counselor observations using the Time Segment Rating System and participant self-report. Tolerability assessments included treatment-emergent adverse events (TEAEs) and vital signs.
Results: Least squares mean (95% CI) treatment differences (combined 50/75 mg SHP465 MAS-placebo) significantly favored SHP465 MAS over placebo for PERMP total score averaged across all postdose assessments (18.38 11.28, 25.47; P < .0001) and at each postdose assessment (all P < .02). Nominal superiority of MAS IR over placebo for PERMP total score averaged across all postdose assessments was observed (nominal P = .0001); treatment differences between SHP465 MAS and MAS IR were not significant (nominal P = .2443). The two most frequently reported TEAEs associated with SHP465 MAS were insomnia (36.5%) and anorexia (21.2%). Mean increases in pulse and blood pressure with SHP465 MAS exceeded those of placebo.
Conclusions: SHP465 MAS (combined 50/75 mg) significantly improved PERMP total score versus placebo, with superiority observed from 2 to 16 h postdose. The tolerability profile of SHP465 MAS was similar to previous reports of SHP465 MAS in adults with ADHD.
Clinical trial registration:
https://clinicaltrials.gov/ct2/show/NCT00928148
identifier is NCT00928148.
To estimate long-term stimulant treatment associations on standardized height, weight, and body mass index trajectories from childhood to adulthood in the Multimodal Treatment Study of ...Attention-Deficit/Hyperactivity Disorder (MTA).
Of 579 children with DSM-IV ADHD-combined type at baseline (aged 7.0-9.9 years) and 289 classmates (local normative comparison group LNCG), 568 and 258 respectively, were assessed 8 times over 16 years (final mean age = 24.7). Parent interview data established subgroups with self-selected Consistent (n = 53, 9%), Inconsistent (n = 374, 66%), and Negligible (n = 141, 25%) stimulant medication use, as well as patients starting stimulants prior to MTA entry (n = 211, 39%). Height and weight growth trajectories were calculated for each subgroup.
Height z scores trajectories differed among subgroups (F = 2.22, p < .0001) and by stimulant use prior to study entry (F = 2.22, p < .001). The subgroup-by-assessment interaction was significant (F = 2.81, p < .0001). Paired comparisons revealed significant subgroup differences at endpoint: Consistent was shorter than Negligible (-0.66 z units /-4.06 cm /1.6 inches, t = -3.17, p < 0.0016), Consistent shorter than Inconsistent (-0.45 z units /-2.74 cm /-1.08 inches, t = -2.39, p < .0172), and the Consistent shorter than LNCG (-0.54 z units/+3.34 cm/ 1.31 inches, t = -3.30, p < 0.001). Weight z scores initially diverged among subgroups, converged in adolescence, and then diverged again in adulthood when the Consistent outweighed the LNCG (+ 3.561 z units /+7.47 kg /+16.46 lb, p < .0001).
Compared with those negligibly medicated and the LNCG, 16 years of consistent stimulant treatment of children with ADHD in the MTA was associated with changes in height trajectory, a reduction in adult height, and an increase in weight and body mass index.
Multimodal Treatment Study of Children With Attention Deficit and Hyperactivity Disorder (MTA); https://clinicaltrials.gov/; NCT00000388.
Short-term, controlled studies of extended-release guanfacine (GXR), a selective alpha(2A)-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.
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.
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 end of the 24-month treatment period. Throughout the entire 2-year study, 202 subjects (77.1%) discontinued and 60 (22.9%) completed the study.
Overall, these data support that GXR monotherapy is generally safe and effective for treating ADHD.
Objectives: Evaluate the efficacy, duration of effect, and safety of 25 mg SHP465 mixed amphetamine salts (MAS) extended-release versus placebo in adults with attention-deficit/hyperactivity disorder ...(ADHD).
Methods: Adults (18-55 years) with ADHD and with ADHD Rating Scale-IV (ADHD-RS-IV) scores ≥24 were randomized to treatment in a double-blind, 2-period, 2-treatment crossover study utilizing the Adult Workplace Environment (AWE), as described by Wigal and Wigal (J Atten Disord 2006;10:92-111). On day 7 of each 7-day treatment period, efficacy was assessed during a 16.5-hour postdose period. The primary endpoint, Permanent Product Measure of Performance (PERMP) total score, was analyzed in the intent-to-treat population using a mixed linear model of analysis of variance. Secondary endpoints, for which the study was not powered, included PERMP problems attempted and answered correctly, ADHD clinician ratings based on counselor observations and inputs during the Time Segment Rating System (Co-ADHD-RS TSRS), and the ADHD self-rating scale (ADHD-SRS). Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and vital signs.
Results: The least squares mean (95% CI) treatment difference (SHP465 MAS-placebo) for PERMP total score significantly favored SHP465 MAS over placebo when averaged across all postdose assessments (19.29 10.95, 27.63; P < 0.0001), with significant treatment differences favoring SHP465 MAS over placebo observed at 4-16 hours postdose (all P < 0.01). TEAEs observed with SHP465 MAS (≥5% of participants) included insomnia, decreased appetite, dry mouth, headache, and anorexia. Mean pulse and blood pressure increases with SHP465 MAS exceeded those of placebo.
Conclusions: SHP465 MAS (25 mg) was superior to placebo on PERMP total score, with treatment differences observed from 4 to 16 hours postdose; nominal treatment differences on the ADHD-SRS, but not the Co-ADHD-RS TSRS, were also observed. The safety and tolerability profile of SHP465 MAS was similar to previous reports for SHP465 MAS and other long-acting stimulants.
Clinical trials registry: clinicaltrials.gov (NCT00202605;
https://clinicaltrials.gov/ct2/show/NCT00202605
)
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