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.
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.
Noting that “the association between adult ADHD and dementia risk remains a topic of interest because of inconsistent results,” an Israeli study team tracked 109,218 members of a nonprofit Israeli health maintenance organization born between 1933 and 1952 who entered the cohort on January 1, 2003, without an ADHD or dementia diagnosis and were followed up to February 28, 2020.
Israeli law forbids nonprofit HMOs from turning anyone away based on demographic factors, health conditions, or medication needs, thereby limiting sample selection bias.
The estimated prevalence of dementia in this HMO, as diagnosed by geriatricians, neurologists, or psychiatrists, is 6.6%. This closely matches estimates in Western Europe (6.9%) and the United States (6.5%).
The team considered, and adjusted for, numerous covariates: age, sex, socioeconomic status, smoking, depression, obesity, chronic obstructive pulmonary disease, hypertension, atrial fibrillation, heart failure, ischemic heart disease, cerebrovascular disease, diabetes, Parkinson’s disease, traumatic brain injury, migraine, mild cognitive impairment, psychostimulants.
With these adjustments, individuals diagnosed with ADHD were almost three times as likely to be subsequently diagnosed with dementia as those without ADHD. Men with ADHD were two and a half times more likely to be diagnosed with dementia, whereas women with ADHD were over three times more likely, than non-ADHD peers.
More concerning still, persons with ADHD were 5.5 times more likely to be subsequently diagnosed with early onset dementia, as opposed to 2.4 times more likely to be diagnosed with late onset dementia.
On the other hand, the team found no significant difference in rates of dementia between individuals with ADHD who were being treated with stimulant medications and individuals without ADHD. Those with untreated ADHD had three times the rate of dementia. The team nevertheless cautioned, “Due to the underdiagnosis of dementia as well as bidirectional misdiagnosis, this association requires further study before causal inference is plausible.”
Conclusions and Relevance:
This study reinforces existing evidence that adult ADHD is associated with an increased risk of dementia. Notably, the increased risk was not observed in individuals receiving psychostimulant medication, however the mechanism behind this association is not clear.
These findings underscore the importance of reliable ADHD assessment and management in adulthood. They also highlight the need for further study into the link between stimulant medications and the decreased risk of dementia.
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