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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News Tuesday: Fidgeting and ADHD

A recent study delved into the connection between fidgeting and cognitive performance in adults with Attention-Deficit/Hyperactivity Disorder. Recognizing that hyperactivity often manifests as fidgeting, the researchers sought to understand its role in attention and performance during cognitively demanding tasks. They designed a framework to quantify meaningful fidgeting variables using actigraphy devices.

(Note: Actigraphy is a non-invasive method of monitoring human rest/activity cycles. It involves the use of a small, wearable device called an actigraph or actimetry sensor, typically worn on the wrist, similar to a watch. The actigraph records movement data over extended periods, often days to weeks, to track sleep patterns, activity levels, and circadian rhythms. In this study, actigraphy devices were used to measure fidgeting by recording the participants' movements continuously during the cognitive task. This data provided objective, quantitative measures of fidgeting, allowing the researchers to analyze its relationship with attention and task performance.)

The study involved 70 adult participants aged 18-50, all diagnosed with ADHD. Participants underwent a thorough screening process, including clinical interviews and ADHD symptom ratings. The analysis revealed that fidgeting increased during correct trials, particularly in participants with consistent reaction times, suggesting that fidgeting helps sustain attention. Interestingly, fidgeting patterns varied between early and later trials, further highlighting its role in maintaining focus over time.

Additionally, a correlation analysis validated the relevance of the newly defined fidget variables with ADHD symptom severity. This finding suggests that fidgeting may act as a compensatory mechanism for individuals with ADHD, aiding in their ability to maintain attention during tasks requiring cognitive control.

This study provides valuable insights into the role of fidgeting in adults with ADHD, suggesting that it may help sustain attention during challenging cognitive tasks. By introducing and validating new fidget variables, the researchers hope to standardize future quantitative research in this area. Understanding the compensatory role of fidgeting can lead to better management strategies for ADHD, emphasizing the potential benefits of movement for maintaining focus.

July 16, 2024

Identifying Autistic-Like Symptoms in Children with ADHD

NEWS TUESDAY: Identifying Autistic-Like Symptoms in Children with ADHD

A recent study investigated the presence of autistic-like symptoms in children diagnosed with Attention Deficit/Hyperactivity Disorder (ADHD). Given the overlapping social difficulties in both ADHD and Autism Spectrum Disorder (ASD), distinguishing between the two disorders can be challenging. This study aims to pinpoint specific patterns of autistic symptoms in children with ADHD, comparing them to those with ASD using the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2).

The research involved 43 school-age children divided into two groups:

  • ADHD Group (25 children): Initially referred for ASD symptoms but later diagnosed with ADHD.
  • ASD Group (18 children): Children diagnosed with ASD.

Researchers used ADOS-2 to evaluate differences in communication deficits, social interaction challenges, and repetitive behaviors between the two groups. The study also compared IQ, age, ADOS-2 domain scores, and externalizing/internalizing problems.

Key Findings:

  • Significant differences were found between the ADHD and ASD groups in ADOS-2 domain scores, including Social Affect, Restricted and Repetitive Behavior, and Total Score.
  • On an individual item level, children with ADHD displayed similar atypical behaviors as those with ASD in social-communication areas such as "Pointing" and "Gestures".
  • Both groups showed comparable frequencies in behaviors like "Stereotyped/idiosyncratic words or phrases", "Mannerisms", and "Repetitive interests and behaviors".

The study highlights the importance of identifying transdiagnostic domains that overlap between ADHD and ASD. The transdiagnostic domain refers to a set of symptoms or behaviors that are common across multiple diagnostic categories rather than being specific to just one. Identifying these domains in mental health practice and in psychological research is crucial to understanding, properly diagnosing, and treating conditions with overlapping features. This understanding could pave the way for tailored treatments addressing the specific needs of children with ADHD, particularly those exhibiting autistic-like symptoms.

July 9, 2024

Non-stimulant Medications for Adults with ADHD: An Overview

NEW STUDY: Non-stimulant Medications for Adults with ADHD: An Overview

Attention-Deficit/Hyperactivity Disorder (ADHD) in adults is commonly treated with stimulant medications such as methylphenidate and amphetamines. However, not all patients respond well to these stimulants or tolerate them effectively. For such cases, non-stimulant medications provide an alternative treatment approach.

Recent research by Brancati et al. reviews the efficacy and safety of non-stimulant medications for adult ADHD. Atomoxetine, a well-studied non-stimulant, has shown significant effectiveness in treating ADHD symptoms in adults. The review highlights the importance of considering dosage, treatment duration, safety, and the presence of psychiatric comorbidities when prescribing atomoxetine.

Additionally, certain antidepressants, including tricyclic compounds, bupropion, and viloxazine, which possess noradrenergic or dopaminergic properties, have demonstrated efficacy in managing adult ADHD. Antihypertensive medications, especially guanfacine, have also been found effective. Other medications like memantine, metadoxine, and mood stabilizers show promise, whereas treatments like galantamine, antipsychotics, and cannabinoids have not yielded positive results.

The expert opinion section of the review emphasizes that while clinical guidelines primarily recommend atomoxetine as a second-line treatment, several other non-stimulant options can be utilized to tailor treatments based on individual patient needs and comorbid conditions. Despite these advancements, the authors call for further research to develop and refine more personalized treatment strategies for adults with ADHD.

This review underscores the growing landscape of non-stimulant treatment options, offering hope for more personalized and effective management of ADHD in adults.

June 25, 2024