February 8, 2021

Long-Acting Liquid Methylphenidate for Treating ADHD in Intellectually Capable Adults with Autism Spectrum Disorder

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.

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Swedish nationwide population study identifies top predictors of ADHD diagnoses among preschoolers

Most preschool-aged children diagnosed with ADHD also exhibit comorbid mental or developmental conditions. Long-term studies following these children into adulthood have demonstrated that higher severity of ADHD symptoms in early childhood is associated with a more persistent course of ADHD. 

The Study: 

Sweden has a single-payer national health insurance system that covers virtually all residents, facilitating nationwide population studies. An international study team (US, Brazil, Sweden) searched national registers for predictors of ADHD diagnoses among all 631,695 surviving and non-emigrating preschoolers born from 2001 through 2007.  

Preschool ADHD was defined by diagnosis or prescription of ADHD medications issued to toddlers aged three through five years old.  

Predictors were conditions diagnosed prior to the ADHD diagnosis. 

A total of 1,686 (2.7%) preschoolers were diagnosed with ADHD, with the mean age at diagnosis being 4.6 years. 

The Numbers:

Adjusting for sex and birth year, the team reported the following predictors, in order of magnitude: 

  • Previous diagnosis of autism spectrum disorder increased subsequent likelihood of ADHD diagnosis twentyfold. 
  • Previous diagnosis of intellectual disability increased subsequent likelihood of ADHD diagnosis fifteenfold. 
  • Previous diagnosis of speech/language developmental disorders and learning disorders, as well as motor and tic disorders, increased subsequent likelihood of ADHD diagnosis thirteen-fold. 
  • Previous diagnosis of sleep disorders increased subsequent likelihood of ADHD diagnosis fivefold. 
  • Previous diagnosis of feeding and eating disorders increased subsequent likelihood of ADHD diagnosis almost fourfold. 
  • Previous diagnosis of gastroesophageal reflux disease (GERD) increased subsequent likelihood of ADHD diagnosis 3.5-fold. 
  • Previous diagnosis of asthma increased subsequent likelihood of ADHD diagnosis 2.4-fold. 
  • Previous diagnosis of allergic rhinitis increased subsequent likelihood of ADHD diagnosis by 70%. 
  • Previous diagnosis of atopic dermatitis or unintentional injuries increased subsequent likelihood of ADHD diagnosis by 50%. 

The Conclusion: 

This large population study underscores that many conditions present in early childhood can help predict an ADHD diagnosis in preschoolers. Recognizing these risk factors early may aid in identifying and addressing ADHD sooner, hopefully improving outcomes for children as they grow

July 2, 2025

Northern Finnish Population Study Finds ADHD Slashes Higher Education Attainment, Comorbidity of ADHD + ODD much worse

Background:

Although ADHD typically begins in childhood, its symptoms frequently continue into adulthood, and it is widely acknowledged as having a lifelong prevalence for most persons with ADHD. 

ADHD symptoms are linked to poor academic performance, mainly due to cognitive issues like compromised working memory. These symptoms lead to long-term negative academic outcomes and difficulty in achieving higher educational degrees. 

Oppositional Defiant Disorder (ODD) often co-occurs with ADHD. In community samples, it appears in about 50–60% of those with ADHD. ODD symptoms include an angry or irritable mood, vindictiveness toward others, and argumentative or defiant behavior that lasts more than 6 months and significantly disrupts daily life.  

Since ODD tends to co-occur with ADHD, research on pure ODD groups without ADHD is limited, especially in community samples. This longitudinal study aimed to examine the impact of ADHD and ODD symptoms in adolescence on academic performance at age 16 and educational attainment by age 32. 

Study:

Finland, like other Nordic countries, has a single-payer health insurance system that includes virtually all residents. A Finnish research team used the Northern Finnish Birth Cohort to include all 9,432 children born from July 1, 1985, through June 30, 1986, and followed since then. 

ADHD symptoms were measured at age 16 using the Strengths and Weaknesses of ADHD symptoms and Normal-behaviors (SWAN) scale. 

Symptoms of ODD were screened using a 7-point rating scale similar to the SWAN scale, based on eight DSM-IV-TR criteria: “Control temper”, “Avoid arguing with adults”, “Follow adult requests or rules”, “Avoid deliberately annoying others”, “Assume responsibility for mistakes or misbehaviour”, “Ignore annoyances from others”, “Control anger and resentment”, and “Control spitefulness and vindictiveness.” 

Higher education attainments were determined at age 32. 

Results:

After adjusting for the educational attainments of the parents of the subjects, family type, and psychiatric disorders other than ADHD or ODD, males with ADHD symptoms at age 16 had a quarter, and females a little over a third, of the higher education attainments of peers without ADHD symptoms at age 32.  

With the same adjustments, males with ODD symptoms alone had two-thirds, and females 80%, of the higher education attainments of peers without ODD, but neither outcome was statistically significant. 

However, all participants with combined ADHD and ODD symptoms at age 16 had roughly one-fifth of the higher education attainments of peers without such symptoms upon reaching age 32. 

Interpretation: 

The team concluded, “The findings that emerged from this large longitudinal birth cohort study showed that the co-occurrence of ODD and ADHD symptoms in adolescence predicted the greatest deficits of all in educational attainment in adulthood.” 

This study highlights the significant, long-lasting impact that co-occurring ADHD and ODD symptoms can have on educational outcomes well into adulthood. It underscores the importance of addressing both disorders together during adolescence to help improve future academic success.

July 1, 2025

U.S. Nationwide Study Finds Down Syndrome Associated with 70% Greater Odds of ADHD

The Background:

Down syndrome (DS) is a genetic disorder resulting from an extra copy of chromosome 21. It is associated with intellectual disability. 

Three to five thousand children are born with Down syndrome each year. They have higher risks for conditions like hypothyroidism, sleep apnea, epilepsy, sensory issues, infections, and autoimmune diseases. Research on ADHD in patients with Down syndrome has been inconclusive. 

The Study:

The National Health Interview Survey (NHIS) is a household survey conducted by the National Center for Health Statistics at the CDC. 

Due to the low prevalence of Down syndrome, a Chinese research team used NHIS records from 1997 to 2018 to analyze data from 214,300 children aged 3 to 17, to obtain a sufficiently large and nationally representative sample to investigate any potential association with ADHD. 

DS and ADHD were identified by asking, “Has a doctor or health professional ever diagnosed your child with Down syndrome, Attention Deficit Hyperactivity Disorder (ADHD), or Attention Deficit Disorder (ADD)?” 

After adjusting for age, sex, and race/ethnicity, plus family highest education level, family income-to-poverty ratio, and geographic region, children and adolescents with Down syndrome had 70% greater odds of also having ADHD than children and adolescents without Down syndrome. There were no significant differences between males and females. 

The Take-Away:

The team concluded, “in a nationwide population-based study of U.S. children, we found that a Down syndrome diagnosis was associated with a higher prevalence of ASD and ADHD. Our findings highlight the necessity of conducting early and routine screenings for ASD and ADHD in children with Down syndrome within clinical settings to improve the effectiveness of interventions.” 

June 27, 2025