November 2, 2023

Taiwanese population study finds reduced risk of influenza among children on sustained methylphenidate treatment, but there's a big catch

While influenza normally only threatens the elderly or those with complicating conditions, the 2009 H1N1 variant struck children particularly hard.

ADHD is known to be associated with inflammatory and immune-related disorders such as asthma, eczema, and allergic rhinitis. These disorders can aggravate respiratory infections such as influenza. Moreover, the cognitive deficits characteristic of ADHD - difficulty following instructions, reduced ability to control impulsive behavior and resulting nail-biting, and poor hand hygiene - can increase the probability of infection in the first place.

A Taiwanese research team explored how drug treatment for ADHD might affect the risk of childhood influenza. Only two drugs are approved in Taiwan for treating ADHD: the stimulant methylphenidate (MPH) and the non-stimulant atomoxetine. Because the latter is only recommended for patients who have unsatisfactory outcomes with MPH, MPH is the drug used in the vast majority of cases.

Taiwan is one of the relatively few countries that track the health care of its entire population in a comprehensive database, thanks to a single-payer health care system launched in1995. From the National Health Insurance Research Database, the Bureau of National Health Insurance in 2005 used random sampling to create a million-person Longitudinal Health Insurance Database (roughly five percent of the population).

From this latter database, the research team identified 9,826 patients newly diagnosed with ADHD. They excluded 1,786 with influenza before their ADHD diagnosis. After further excluding those outside the youth age brackets or who had gotten a flu shot during the year preceding enrollment, they were left with 5,259 patients with ADHD under age 18. Of these, 661 got influenza following diagnosis of ADHD.

In this ADHD cohort, 43 percent had not used any medication. Of the 57% who used medication, 20 percent did so for 90 days or less, and 37 percent for over 90 days.

After controlling for gender, age, level of urbanization, psychiatric or physical illnesses, and other medication use(sedative/hypnotics/anxiolytics), those prescribed MPH over 90 days were 38 percent less likely to get influenza requiring interaction with the health care system. There was a lesser reduction for those taking MPH 90 days or less, but it was not statistically significant.

A significant limitation is the fact that data from in-school vaccination programs are not included in the database used. If children receiving less or no medication were also less likely to be vaccinated, this unexplored covariate could explain the results. Further study is needed.

Hsuan Lee, VincentChin-Hung Chen, Yao-Hsu Yang , Ting-Yu Kuo, Tzu-Chin Lin, Shu-I Wu, Kai-LiangKao, Jun-Cheng Weng, Brent Allan Kelsen, Sophie Hsin-Yi Liang, "Decreased Risk of Influenza in Child and Adolescent Patients with Attention-Deficit Hyperactivity DisorderFollowing Methylphenidate Treatment: A Nationwide Cohort Study in Taiwan," NeuropsychiatricDisease and Treatment (2020), 16: 1309-1319, https://doi.org/10.2147/NDT.S242519.

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Meta-analysis Finds Little Evidence in Support of Game-based Digital Interventions for ADHD

ADHD treatment usually involves a combination of medication and behavioral therapy. However, medication can cause side effects, adherence problems, and resistance from patients or caregivers. 

Numerous systematic reviews and meta-analyses have evaluated the effects of non-pharmacological interventions on ADHD. With little research specifically examining game-based interventions for children and adolescents with ADHD or conducting meta-analyses to quantify their treatment effectiveness, a Korean study team performed a systematic search of the peer-reviewed medical literature to do just that.  

The Study: 

To be included, studies had to be randomized controlled trials (RCTs) that involved children and adolescents diagnosed with ADHD. The team excluded RCTs that included participants with psychiatric conditions other than ADHD.  

Eight studies met these standards. Four had a high risk of bias.  

Meta-analysis of four RCTs with a combined total of 481 participants reported no significant improvements in either working memory or inhibition from game-based digital interventions relative to controls. 

Likewise, meta-analysis of three RCTs encompassing 160 children and adolescents found no significant improvement in shifting tasks relative to controls. 

And meta-analysis of two RCTs combining 131 participants reported no significant gains in initiating, planning, organizing, and monitoring abilities, nor in emotional control

The only positive results were from two RCTs with only 90 total participants that indicated some improvement in visuospatial short-term memory and visuospatial working memory.  

There was no indication of effect size, because the team used mean differences instead of standardized mean differences.  

Conclusion:

The team concluded, “The meta-analysis revealed that game-based interventions significantly improved cognitive functions: (a) visuospatial short-term memory … and (b) visuospatial working memory … However, effects on behavioral aspects such as inhibition and monitoring … were not statistically significant, suggesting limited behavioral improvement following the interventions.” 

Simply put, the current evidence does not support the effectiveness of game-based interventions in improving behavioral symptoms of ADHD in children and adolescents. The only positive results were from two studies with a small combined sample size, which does not qualify as a genuine meta-analysis. All the other meta-analyses performed with larger sample sizes reported no benefits. 

Understanding Teen Health and Well-being in ADHD: A Fresh Perspective from the CDC

Recent research from the Centers for Disease Control and Prevention (CDC) highlights distinct health and social-emotional challenges faced by teens diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD). This study, published in the Journal of Developmental and Behavioral Pediatrics, offers critical insights directly from the teens themselves, providing a unique view often missed when relying solely on parent or clinical reports. 

Researchers analyzed nationally representative data from July 2021 through December 2022, comparing self-reported experiences of teens aged 12 to 17 with and without ADHD. Approximately 10% of teenagers had an ADHD diagnosis, and the findings reveal specific areas where teens with ADHD face notable difficulties. 

Teenagers with ADHD reported significantly higher rates of bullying victimization and struggles in making friends compared to their peers. Surprisingly, they were less likely to report a lack of peer support, suggesting complexities in how they perceive friendships and social networks. The study underscores the importance of directly engaging teens in assessing their social relationships, rather than solely relying on parental perspectives. 

Sleep difficulties emerged as another critical issue for teens with ADHD. About 80% reported problems like difficulty waking up and irregular wake times, markedly higher than their non-ADHD counterparts. Such disruptions can exacerbate attention difficulties and emotional regulation issues, further complicating daily life for these teens. 

Excessive screen time also stood out, with nearly two-thirds of teens with ADHD spending over four hours daily on screens, excluding schoolwork. This high screen usage is concerning, given its potential negative impact on physical and mental health, including sleep quality and social interactions. 

Notably, the study found no significant differences in physical activity levels or concerns about weight between teens with and without ADHD. This finding contrasts with previous studies that have highlighted lower physical activity among children with ADHD, suggesting the need for continued research on how physical activity is measured and encouraged in this population. 

The study’s authors emphasize the importance of health promotion interventions tailored specifically for teens with ADHD. By directly engaging teens and considering their unique perspectives, interventions can better address social-emotional well-being and healthy lifestyle behaviors, ultimately improving long-term outcomes for this vulnerable group. 

Overall, this research provides compelling evidence for healthcare providers, educators, and families to focus on supporting teens with ADHD in areas of social skills, sleep hygiene, and healthy screen time habits. Such targeted support can significantly enhance the quality of life and health outcomes for adolescents navigating the challenges of ADHD. 

Meta-analysis Reports No Significant Evidence for Efficacy of Neuromechanistic Treatments for Adult ADHD

The Background on ADHD Treatments, rTMS and tDCS:

Methylphenidate is known as the gold-standard treatment for ADHD, increasing dopamine concentrations and helping to focus. However, these psychostimulants may be less well-tolerated in adults. Adverse effects include decreased appetite, nausea, racing heartbeat, restlessness, nervousness, and insomnia. 

Neurofeedback is a non-pharmaceutical treatment that combines cognitive behavioral therapy techniques like conditioning and positive reinforcement with electroencephalography (EEG) feedback. Electrodes are placed on specific brain areas, guiding patients to regulate their brainwave activity. 

Repetitive transcranial magnetic stimulation (rTMS) uses electromagnetism to induce an electric field by passing a magnetic field through the scalp. Transcranial direct current stimulation (tDCS), on the other hand, directly applies an electric current through the scalp. Both repetitive transcranial magnetic stimulation (rTMS) and tDCS primarily target the outermost layers of neurons, as they are non-invasive methods. Nevertheless, both techniques are believed to affect deeper layers through interconnected neuronal networks.  

The Study:

A French research team conducted a systematic search of the peer-reviewed medical literature to perform a meta-analysis to explore the efficacy of these experimental treatment techniques. 

Eight studies – four using rTMS and another four using tDCS – met the inclusion criteria. Studies had to be randomized controlled trials (RCTs), and had to involve multiple sessions of treatment. Participants had to be adults previously diagnosed with ADHD.  

Outcomes were measured through self-rated scales, neuropsychological tests, and electrophysiological pre-post evaluations. 

Separate meta-analyses of the four tDCS RCTs combining 154 participants and of the four rTMS RCTs encompassing 149 participants likewise reported no significant improvements. In all cases variation in outcomes between studies was moderate, and there were no signs of publication bias. 

The Conclusion on Neuromechanistic Treatments for ADHD:

Meta-analysis of all eight studies with a combined total of 421 participants reported no significant improvements over controls. Narrowing down to studies that used sham controls likewise produced no significant improvements. So, despite the title of this study, these neuromechanistic treatments do not appear to be the future of treatment for adult ADHD.