May 22, 2024

Meta-analysis from Worldwide Data Finds Greater Co-occurrence of Epilepsy and ADHD Than Expected

Noting that the degree of comorbidity (co-occurrence) between epilepsy and ADHD “has never been quantified based on a systematic review with meta-analysis,” a Chinese study team based at Wuhan university has just reported findings based on doing just that. 

Their systematic search of the peer-reviewed medical literature yielded 17 studies examining the prevalence of epilepsy among persons with ADHD, and 49 studies measuring the prevalence of ADHD among persons with epilepsy.

According to the Apple dictionary app, epilepsy is “a neurological disorder marked by sudden recurrent episodes of sensory disturbance, loss of consciousness, or convulsions, associated with abnormal electrical activity in the brain.” Its lifetime prevalence in the general population is about 0.76%, or about one in every 130 persons.

Meta-analysis of 17 studies with a combined total of over 900,000 participants spread over twelve countries on five continents yielded an epilepsy prevalence estimate of 3.4% among individuals with ADHD, or well over four times the prevalence in the general population. There was no sign of publication bias, but variability (heterogeneity) among studies was extremely high.

The worldwide prevalence of ADHD in children, on the other hand, is about 7.2%, affecting roughly one in fourteen.

Meta-analysis of 49 studies with a combined total of 172,206 persons from 16 countries on five continents reported an ADHD prevalence of just over 22% among persons with epilepsy. However, heterogeneity among studies was extremely high, and there was very strong evidence of publication bias. 

Using the trim-and-fill correction for publication bias yielded a reduced estimate of 16%, which is still over twice the prevalence in the general population.

Furthermore, the authors noted, “Given that the large sample studies in this study are basically population-based studies and the small sample studies are hospital-based studies, there is also the possibility of Berkson’s bias. Specifically, patients with comorbidities are more likely to need help or seek medical advice. This possibility would yield a higher comorbidity rate in hospital-based studies.”

And that is exactly what emerged from subgroup analysis. The prevalence of ADHD in epilepsy among the hospital-based studies was 27.1%, over twice the 13.2% prevalence reported from the 13 population-based studies. The largest population-based study, a U.S. study with over 114,000 participants, yielded a prevalence of only 3.5%.

The authors cautioned that the very high degree of heterogeneity between studies indicates “it is inappropriate to consider the summary effect as representative of the real effect.”

Shun, Wang & Yao, Baozhen & Haiju, Zhang & Xia, Liping & Yu, Shiqian & Peng, Xia & Xiang, Dan & Liu, Zhongchun. (2023). Comorbidity of epilepsy and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Journal of Neurology. 270. 1-13. 10.1007/s00415-023-11794-z.

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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