February 8, 2021
A team from Harvard Medical School and Massachusetts General Hospital conducted a six-week open-label trial of liquid-formulation extended-release methylphenidate (MPH-ER) to treat ADHD in adults with high-functioning autism spectrum disorder (HF-ASD). ASD is a lifelong disorder with deficits in social communication and interaction and restricted, repetitive behaviors. Roughly half of those diagnosed with ASD also are diagnosed with ADHD.
This was the first stimulant trial in adults with both ASD and ADHD. There were twelve male and three female participants, all with moderate to severe ADHD, and in their twenties, with IQ scores of at least 85.
Use of a liquid formulation enabled doses to be raised very gradually, starting with a daily dose of 5mg (1mL) and titrating up to 60mg over the first three weeks, then maintaining that level through the sixth week. Participants were reevaluated for ADHD symptoms every week during the six-week trial. Severity of ASD was assessed at the start, midpoint, and conclusion of the trial, as were other psychiatric symptoms.
Prior to the trial, researchers agreed on a combination of targets on two clinician-rated scoring systems that would have to be reached for treatment to be considered successful. One is a score of 2 or less on the CGI-S, a measure of illness severity, with scores ranging from 1 (normal, not at all ill) to 7 (most extremely ill). The other, a reduction of at least 30 percent in the AISRS score, which combines each of 18 symptoms of ADHD on a severity grid (0=not present; 3=severe; overall minimum score: 0; overall maximum score: 54).
At the conclusion of the trial, twelve of the fifteen patients (80 percent) met the preset conditions for success. Fully fourteen (93 percent) saw a ≥ 30 percent reduction in their AISRS score, while twelve scored ≤ 2 on illness severity.
However, when using the patient-rated ASRS scoring system, only five (33 percent) saw a ≥ 30 percent reduction in ADHD severity.
Thirteen participants (87 percent) reported at least one adverse event, and nine (60 percent) reported two or more. One reported a serious adverse event (attempted suicide) in a patient with multiple prior attempts. Because the attempt was not deemed due to medication they continued in and completed the trial. Seven participants experienced titration-limiting adverse events (headaches, palpitations, jaw pain, and insomnia). Headache was most frequent (53%), followed by insomnia and anxiety (33% each), and decreased appetite (27%).
During the trial, weight significantly decreased, while pulse significantly increased. There were no significant differences in other vital and cardiovascular measurements.
The authors concluded, “this OLT of short-term MPH-ER therapy documents that acute treatment with MPH-ER in young adults with ASD was associated with significant improvement in ADHD symptoms, mirroring the typically-expected magnitude of response observed in adults with only ADHD. Treatment with MPH-ER was well-tolerated, though associated with a higher than expected frequency of adverse events.”
They also cautioned, “The results of this study need to be considered in light of some methodological limitations. This was an open-label study; therefore, assessments were not blind to treatment. We did not employ a placebo control group and, therefore, cannot separate the effects of treatment from time or placebo effects. … firmer conclusions regarding the safety and efficacy of MPH-ER for the treatment of ADHD in HF-ASD populations await results from larger, randomized, placebo-controlled clinical trials.”
Gagan Joshi, Maura DiSalvo, Janet Wozniak, T. Atilla Ceranoglu, Amy Yule, Craig Surman, Ronna Fried, Maribel Galdo, Barbora Hoskova, Abigail Belser & Joseph Biederman, “A Prospective Open-Label Trial of Long-Acting Liquid Methylphenidate for the Treatment of Attention Deficit/Hyperactivity Disorder in Intellectually Capable Adults with Autism Spectrum Disorder,” The World Journal of Biological Psychiatry (2019) DOI: 10.1080/15622975.2019.1679392.
Background:
Noting that “Previous research has demonstrated that attention significantly influences various domains such as language, literacy, and mathematics, making it a crucial determinant of academic achievement,” an international study team performed a comprehensive search of the peer-reviewed medical literature for studies evaluating effects of physical activity on attention.
The Study:
The team’s meta-analysis of ten studies with a combined total of 474 participants found moderate reductions in attention problems following physical activity. They found no significant evidence of publication bias, but there was considerable variation in outcomes between studies (heterogeneity).
To tease out the reasons for this variability, the team looked at specific attributes of the physical activity regimens used in the studies.
The seven studies with 168 participants that involved mentally engaging physical activity reported large reductions in attention problems, whereas the three studies with 306 persons that used aerobic exercise found no reduction whatsoever. Heterogeneity in the former was reduced, in the latter all but disappearing.
Comparing studies with other interventions as control groups (6 studies, 393 participants) with those with no intervention as control (4 studies, 81 participants), the former reported only small improvements in attention problems, while the latter reported large improvements.
Duration of physical activity made little difference. The four studies with physical activity of an hour or more reported better outcomes than the six with less than an hour, but the difference was not significant.
Greater frequency did make a difference, but in a counterintuitive way. The seven studies with one or two physical activity interventions per week (162 participants) reported large reductions in attention problems, whereas the three studies with three or more interventions per week (312 participants) showed no improvement.
Conclusion:
The authors concluded, “Our study suggests that cognitively engaging exercise is more effective in improving attention problems in school-aged children with ADHD.” Moreover, “the benefits of improved attention in school-age children with ADHD are not necessarily positively correlated with higher frequency and longer duration of physical activity.” Also keep in mind that exercise, while important for all children, should not replace medical and psychological treatments for the disorder.
The National Health Interview Survey (NHIS) is conducted annually by the National Center for Health Statistics at the Centers for Disease Control and Prevention. The NHIS is done primarily through face-to-face computer-assisted interviews in the homes of respondents. But telephone interviews are substituted on request, or where travel distances make in-home visits impractical.
For each interviewed family, only one sample child is randomly selected by a computer program.
The total number of households with a child or adolescent aged 3-17 for the years 2018 through 2021 was 26,422.
Based on responses from family members, 9.5% of the children and adolescents randomly surveyed throughout the United States had ADHD.
This proportion varied significantly based on age, rising from 1.5% for ages 3-5 to 9.6% for ages 6-11 and to 13.4% for ages 12-17.
There was an almost two-to-one gap between the 12.4% prevalence among males and the 6.6% prevalence among females.
There was significant variation by race/ethnicity. While rates among non-Hispanic whites (11.1%) and non-Hispanic blacks (10.5%) did not differ significantly, these two groups differed significantly from Hispanics (7.2%) and Others (6.6%).
There were no significant variations in ADHD prevalence based on highest education level of family members.
But family income had a significant relationship with ADHD prevalence, especially at lower incomes. For family incomes under the poverty line, the prevalence was 12.7%. That dropped to 10.3% for family incomes above the poverty level but less than twice that level. For all others it dropped further to about 8.5%. Although that might seem like poverty causes ADHD, we cannot draw that conclusion. Other data indicate that adults with ADHD have lower incomes. That would lead to more ADHD in kids from lower income families.
There was also significant geographic variation in reported prevalence rates. It was highest in the South, at 11.3%, then the Midwest at 10%, the Northeast at 9.1%, with a jump down to 6.9% in the West.
Overall ADHD prevalence did not vary significantly by year over the four years covered by this study.
This study highlights a consistently high prevalence of developmental disabilities among U.S. children and adolescents, with notable increases in other developmental delays and co-occurring learning and intellectual disabilities from 2018 to 2021. While the overall prevalence remained stable, these findings emphasize the need for continued research into potential risk factors and targeted interventions to address developmental challenges in youth.
It is also important to note that this study assessed the prevalence of ADHD being diagnosed by healthcare professionals. Due to variations in healthcare accessibility across the country, the true prevalence of ADHD may differ still.
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Background:
An international research team used the nationally representative 2020–2021 U.S. Survey of Children’s Health to explore associations between ADHD, weeknight sleep insufficiency, and bedtime irregularity.
"Sleep sufficiency" refers to the recommended amount of sleep for an individual. Sleep recommendations vary by age and other factors, such as health and lifestyle. For example, 7-9 hours is typically considered sufficient sleep for most adults, but an active teen may require closer to 10 hours of sleep per day.
Previous studies have shown that issues with both falling and staying asleep are common in individuals with ADHD.
The Study:
The team matched 7,671 children and adolescents with ADHD aged 3-17 to 51,572 controls.
Noting that “The few available population-based studies examining sleep in children with ADHD have focused on circumscribed age ranges, limiting generalizability across childhood, and have seldom included controls,” and “bedtime irregularity has received limited empirical attention in children with ADHD,” this study focused on these aspects of sleep impairment.
The study group excluded children and adolescents with ADHD with Down syndrome, current or lifetime cerebral palsy, and current or lifetime intellectual disability. In the control group, it excluded individuals with Down syndrome, cerebral palsy, intellectual disability, speech and language disorder, autism spectrum disorder, ADHD, anxiety, depression, behavioral or conduct problems, Tourette syndrome, and use of mental health services in the preceding 12 months. These groups were excluded to limit potential confounding factors.
After adjustment for covariates, parents of children and adolescents with ADHD reported weekday sleep insufficiency 65% more frequently than parents of controls.
However, when comparing matched controls with children and adolescents with ADHD who were being treated with ADHD medication, there was no significant difference.
Similarly, there was a small but significant effect size increase in bedtime irregularity among children and adolescents with ADHD relative to their matched controls.
Yet there was also a small but significant effect size decrease in bedtime irregularity among those taking medication for ADHD relative to those who were unmedicated.
The team noted, “Interestingly, here, ADHD medication use was linked to less bedtime irregularity across full and age-stratified samples, and not related to sleep insufficiency. However, research indicates the association between stimulant use and sleep problems is attenuated with longer duration of use, and also suggests the potential for stimulants to produce positive effects on sleep through reduced bedtime resistance. Further, ADHD medication type, not specified, may have influenced outcomes.”
The Take-Away:
The study concluded that ADHD in children was linked to insufficient sleep and irregular bedtimes in a nationally representative sample, reinforcing and expanding previous research. The findings emphasize the influence of various factors on sleep insufficiency and bedtime irregularity, including race, screen time, poverty, ADHD severity, and depression.
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