January 18, 2024

Meta-analysis of randomized controlled trials inconclusive on EEG neurofeedback treatment for ADHD

Noting that “The efficacy of surface electroencephalographic neurofeedback (EEG‐NF) for improving attentional performance assessed by laboratory measures in patients with attention‐deficit/hyperactivity disorder (ADHD) remains unclear,” a Taiwanese study team systematically searched seven databases, including the U.S. clinical trials database, for randomized controlled trials (RCTs) through January of 2022.

They identified fourteen RCTs with a combined 718 participants that met criteria for inclusion in meta-analysis. The net outcome was a small-to-medium effect size improvement in attentional performance for participants receiving EEG neurofeedback by contrast with “comparators.” 

The comparators varied widely: waitlist, treatment as usual, physical exercise, behavioral therapy, attention skills training, computer-aided attention training, medications, electromyographic biofeedback, sham EEG neurofeedback. This alone brings into question the meta-analysis outcome.

But there were additional methodological shortcomings. There was strong evidence of publication bias. And though the authors promised, “On encountering funnel plot asymmetry, potentially missing studies were imputed by using the Duval and Tweedie’s trim and fill method,” they never shared the outcome.

Another shortcoming was that only two of the fourteen RCTs blinded the participants, meaning that in twelve RCTs the participants were likely to be aware they were in the EEG neurofeedback group rather than the control group. And that made all the difference. The twelve unblinded RCTs were responsible for all the small-to-medium effect size improvement. There was no sign of improvement in the two blinded RCTs.

The authors tried to give a positive spin to these results, stating “our results supported the use of surface EEG-NF for improving attentional performance through the modulation of basic neurocognitive functioning in patients with ADHD,” while conceding, “However, given the small number of trials and the poor methodological qualities regarding blinding, our findings need to be judiciously interpreted and warrant further investigations for validation.”

A more candid assessment of this meta-analysis would be the one they began with: “The efficacy of surface electroencephalographic neurofeedback (EEG‐NF) for improving attentional performance assessed by laboratory measures in patients with attention‐deficit/hyperactivity disorder (ADHD) remains unclear.”

Hsien‐Jane Chiu, Cheuk‐Kwan Sun, Hsin‐Yi Fan, Ruu‐Fen Tzang, Ming‐Yu Wang, Ying‐Chih Cheng, Yu‐Shian Cheng, Pin‐Yang Yeh, and Weilun Chung, “Surface electroencephalographic neurofeedback improves sustained attention in ADHD: a meta-analysis of randomized controlled trials” Child and Adolescent Psychiatry and Mental Health (2022), 16:104, https://doi.org/10.1186/s13034-022-00543-1.

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NEW STUDY: Understanding the Gap Between ADHD Clinical Trials and Real-World Patients

Background 

ADHD (Attention-Deficit/Hyperactivity Disorder) is one of the most studied neurodevelopmental conditions, with many clinical trials evaluating the effectiveness and safety of various medications. These trials, known as randomized controlled trials (RCTs), are considered the gold standard for assessing treatments. However, strict eligibility criteria often exclude many real-world patients, raising questions about whether the findings from these trials apply to everyday clinical settings.

Our latest study sheds light on this issue, revealing just how many individuals with ADHD might be excluded from RCTs and the impact this exclusion has on their treatment outcomes. 

Method

Researchers used Swedish national registries to analyze data from 189,699 individuals diagnosed with ADHD who started medication between 2007 and 2019. They applied exclusion criteria from 164 international RCTs to identify who would have been considered ineligible for these trials in order to determine the proportion of individuals with ADHD who would not meet the eligibility criteria for RCTs.  

Key Findings

Many Patients Are Ineligible for Clinical Trials:

  • Over half (53%) of the study population would have been ineligible for ADHD medication trials.
  • Adults were most likely to be excluded (74%), followed by adolescents (35%) and children (21%).

Ineligible Patients Face Unique Challenges:

  • Treatment Switching: Ineligible individuals were more likely to switch medications within the first year (14% higher likelihood compared to eligible patients).
  • Medication Discontinuation: They were slightly less likely to stop taking their medication during the first year.

Higher Risk of Adverse Outcomes:

  • Ineligible patients experienced significantly higher rates of psychiatric hospitalizations and health issues such as depression, anxiety, and substance use disorders. For instance:some text
    • Psychiatric hospitalizations: Nearly 10 times more likely.
    • Specialist visits for substance use disorders: About 15 times more likely.
    • Anxiety-related visits: Over 11 times more likely.

What This Means

These findings highlight a major gap between the controlled environments of clinical trials and the realities faced by individuals with ADHD in everyday life. While RCTs provide valuable insights, their restrictive criteria often exclude patients with more complex health profiles or co-existing conditions. This limits the generalisability of trial results, meaning that treatment guidelines based solely on RCTs may not fully address the needs of all patients.

Conclusion

This study demonstrated that a significant proportion of individuals with ADHD, particularly adults, do not meet the eligibility criteria for standard RCTs. These results emphasize the importance of bridging the gap between research settings and real-world applications. By recognizing and addressing the limitations of RCTs, we can work towards more equitable and effective ADHD treatment strategies for everyone.

January 14, 2025

Where Does ADHD Fit in the Psychopathology Hierarchy? A Symptom-Focused Study

NEWS TUESDAY: Where Does ADHD Fit in the Psychopathology Hierarchy? A Symptom-Focused Study

Background:

Our understanding of Attention-deficit/hyperactivity disorder (ADHD) has grown and evolved considerably since it first appeared in the DSM-II as “Hyperkinetic Reaction of Childhood.”  This study aimed to find the disorder’s placement within the modern psychopathology classification systems like the Hierarchical Taxonomy Of Psychopathology (HiTOP). 

The HiTOP model aims to address limitations of traditional classification systems for mental illness, such as the DSM-5 and ICD-10, by organizing psychopathology according to evidence from research on observable patterns of mental health problems.. Is ADHD best categorized under externalizing conditions, neurodevelopmental disorders, or something else entirely? A recent study by Zheyue Peng, Kasey Stanton, Beatriz Dominguez-Alvarez, and Ashley L. Watts takes a closer look at this question using a symptom-focused approach.

The Study:

Traditionally, ADHD has been associated with externalizing behaviors, such as impulsivity and hyperactivity, or with neurodevelopmental traits, like cognitive delays. However, this study challenges the idea of placing ADHD into a single category. Instead, it maps ADHD symptoms across three major psychopathology spectra: externalizing, neurodevelopmental, and internalizing.

The findings reveal that ADHD symptoms don’t fit neatly into one box. For example, symptoms like impulsivity, poor school performance, and low perseverance were strongly associated with externalizing behaviors. On the other hand, cognitive disengagement (e.g., daydreaming, blank staring) and immaturity were closely linked to neurodevelopmental challenges. Interestingly, cognitive disengagement also showed ties to internalizing symptoms, such as anxiety or depression.

This research underscores the complexity of ADHD. Rather than treating ADHD as a single, unitary construct, the study advocates for a symptom-based approach to better understand and treat individuals. By acknowledging that ADHD symptoms relate to multiple psychopathology spectra, clinicians and researchers can move toward more nuanced classification systems and targeted interventions.

Conclusion: 

Ultimately, this study highlights the need for modern systems to move beyond rigid categories and adopt a more flexible, symptom-focused framework for understanding ADHD’s place in psychopathology.

January 6, 2025

No Link Found Between Maternal Coffee Consumption and Subsequent Neurodevelopmental Difficulties

Norwegian nationwide population study finds no link between maternal coffee consumption during pregnancy and offspring neurodevelopmental difficulties, including ADHD

The Background:

Caffeine and its primary breakdown compounds – paraxanthine, theophylline, and theobromine (also the primary alkaloid in chocolate) – readily cross the placenta and tend to linger due to the underdevelopment of fetal caffeine metabolizing enzymes.

Could accumulating caffeine metabolites harm the developing fetal brain? Studies to date have come to contradictory conclusions, some finding an association, others finding none.

Norway has a national single-payer health insurance system with a national health registry comprehensively tracking virtually all residents.

The Methods:

An international study team used Norways’s registry, and its Mother, Father, and Child Cohort Study (MoBa) to explore the relationship between maternal and paternal coffee consumption and offspring neurodevelopmental difficulties (ND), including symptoms of ADHD as determined from validated rating scales, using 58,964 mother-child pairs and 22,576 father-child pairs, covering the decade 1999-2008.

Unadjusted results indicated a strong association between maternal coffee consumption before and during pregnancy with offspring ADHD, but none with paternal coffee consumption. Superficially, that might seem like compelling evidence.

Yet after adjusting for education, income, smoking, and alcohol, “previously significant effects attenuated towards zero and some associations switched from being positive to negative.”

Then, after further adjusting for genetic confounding, ADHD symptoms at 1.5 years, 3 years, 5 years (on both of two different rating scales), and 8 years (including separate measures of inattention and hyperactivity symptoms) all became indistinguishable between offspring from mothers consuming coffee during pregnancy and offspring of mothers abstaining from coffee during pregnancy. 

Conclusion:

The team concluded, “This study applied several conventional and genetic epidemiological approaches to investigate the potential relationship between maternal coffee consumption during pregnancy and offspring NDs [neurodevelopmental difficulties]. When considering the results of the conventional and genetic epidemiological analyses, as well as the broader literature, we conclude that there is little evidence that maternal coffee consumption during pregnancy is strongly causally related to offspring NDs.”

More specifically, the team found no evidence of any causal relationship with offspring ADHD

January 2, 2025