April 23, 2021

What is Evidenced-Based Medicine?

With the growth of the Internet, we are flooded with information about attention deficit hyperactivity disorder from many sources, most of which aim to provide useful and compelling "facts" about the disorder.  But, for the cautious reader, separating fact from opinion can be difficult when writers have not spelled out how they have come to decide that the information they present is factual. 

My blog has several guidelines to reassure readers that the information they read about ADHD is up-to-date and dependable. They are as follows:

Nearly all the information presented is based on peer-reviewed publications in the scientific literature about ADHD. "Peer-reviewed" means that other scientists read the article and made suggestions for changes and approved that it was of sufficient quality for publication. I say "nearly all" because in some cases I've used books or other information published by colleagues who have a reputation for high-quality science.

When expressing certainty about putative facts, I am guided by the principles of evidence-based medicine, which recognizes that the degree to which we can be certain about the truth of scientific statements depends on several features of the scientific papers used to justify the statements, such as the number of studies available and the quality of the individual studies. For example, compare these two types of studies.  One study gives drug X to 10 ADHD patients and reported that 7 improved.  Another gave drug Y to 100 patients and a placebo to 100 other patients and used statistics to show that the rate of improvement was significantly greater in the drug-treated group. The second study is much better and much larger, so we should be more confident in its conclusions. The rules of evidence are fairly complex and can be viewed at the Oxford Center for Evidenced Based Medicine (OCEBM;http://www.cebm.net/).


The evidenced-based approach incorporates two types of information: a) the quality of the evidence and b) the magnitude of the treatment effect. The OCEBM levels of evidence quality are defined as follows (higher numbers are better:

  1. Mechanism-based reasoning.  For example, some data suggest that oxidative stress leads to ADHD, and we know that omega-3 fatty acids reduce oxidative stress. So there is a reasonable mechanism whereby omega-3 therapy might help ADHD people.
  2. Studies of one or a few people without a control group, or studies that compare treated patients to those that were not treated in the past.

Non-randomized, controlled studies.    In these studies, the treatment group is compared to a group that receives a placebo treatment, which is a fake treatment not expected to work.  

  1. Non-randomized means that the comparison might be confounded by having placed different types of patients in the treatment and control groups.
  2. A single randomized trial.  This type of study is not confounded.
  3. Systematic review and meta-analysis of randomized trials. This means that many randomized trials have been completed and someone has combined them to reach a more accurate conclusion.

It is possible to have high-quality evidence proving that a treatment works but the treatment might not work very well. So it is important to consider the magnitude of the treatment effect, also called the "effect size" by statisticians. For ADHD, it is easiest to think about ranking treatments on a ten-point scale. The stimulant medications have a quality rating of 5 and also have the strongest magnitude of effect, about 9 or 10.Omega-3 fatty acid supplementation 'works' with a quality rating of 5, but the score for the magnitude of the effect is only 2, so it doesn't work very well. We have to take into account patient or parent preferences, comorbid conditions, prior response to treatment, and other issues when choosing a treatment for a specific patient, but we can only use an evidence-based approach when deciding which treatments are well-supported as helpful for a disorder.

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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.