June 20, 2024
In December 2016, the U.S. Food and Drug Administration (FDA) warned “that repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children’s brains.” The FDA adds, “Health care professionals should balance the benefits of appropriate anesthesia against the potential risks, especially for procedures lasting longer than 3 hours or if multiple procedures are required in children under 3 years,” and “Studies in pregnant and young animals have shown that using these drugs for more than 3 hours caused widespread loss of brain nerve cells.”
That raises a concern that such exposure could lead to increased risk of psychiatric disorders, including ADHD.
Noting “There are inconsistent reports regarding the association between general anesthesia and adverse neurodevelopmental and behavioral disorders in children,” a South Korean study team conducted a nationwide population study to explore possible associations through the country’s single-payer health insurance database that covers roughly 97% of all residents.
The team looked at the cohort of all children born in Korea between 2008 and 2009, and followed them until December 31, 2017. They identified 93,717 children in this cohort who during surgery received general anesthesia with endotracheal intubation (a tube inserted down the trachea), and matched them with an equal number of children who were not exposed to general anesthesia.
The team matched the unexposed group with the exposed group by age, sex, birth weight, residential area at birth, and economic status.
They then assessed both groups for subsequent diagnoses of ADHD.
In general, children exposed to general anesthesia were found to have a 40% greater risk of subsequently being diagnosed with ADHD than their unexposed peers.
This effect was found to be dose dependent by several measures:
All three measures were highly significant.
The authors concluded, “exposure to general anesthesia with ETI [endotracheal intubation] in children is associated with an increased risk of ADHD … We must recognize the possible neurodevelopmental risk resulting from general anesthesia exposure, inform patients and parents regarding this risk, and emphasize the importance of close monitoring of mental health. However, the risk from anesthesia exposure is not superior to the importance of medical procedures. Specific research is needed for the development of safer anesthetic drugs and doses.”
Joo Young Song, Hye Ryeong Cha, Seung Won Lee, Eun Kyo Ha, Ju Hee Kim, and Man Yong Han, “Association Between Receipt of General Anesthesia During Childhood and Attention Deficit Hyperactive Disorder and Neurodevelopment,” Journal of Korean Medical Science (2023), 38(6):e42, https://doi.org/10.3346/jkms.2023.38.e42.
U.S. Food and Drug Administration, “FDA Drug Safety Podcast: FDA review results in new warnings about using general anesthetics and sedation drugs in young children and pregnant women,” January 14, 2022, https://www.fda.gov/drugs/fda-drug-safety-podcasts/fda-drug-safety-podcast-fda-review-results-new-warnings-about-using-general-anesthetics-and-sedation.
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:
Ineligible Patients Face Unique Challenges:
Higher Risk of Adverse Outcomes:
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.
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.
Exposure to heavy metals like lead, arsenic, mercury, cadmium, and manganese is known to harm developing nervous systems. However, past studies on whether heavy metals specifically increase the risk of ADHD have shown mixed results.
A research team from China (Gu et al., 2024) reviewed medical studies and conducted meta-analyses to better understand this issue.
The team included studies on children and teens, focusing on cohort studies, case-control studies, and cross-sectional studies. They only used articles written in English and required validated biomonitoring (like blood tests) to measure heavy metal exposure. ADHD diagnoses had to come from clinical evaluations.
To be included, studies had to report effect sizes such as odds ratios and relative risks with confidence intervals. The team focused on comparisons between groups with high, low, or no exposure, which made it harder to analyze dose-response relationships.
They also evaluated the quality of each study. All cohort studies were rated high-quality. Of the 15 case-control studies, 6 were high-quality, and 9 were moderate-quality. Among cross-sectional studies, only 2 were high-quality, and the rest were moderate-quality.
There was no evidence linking ADHD to other heavy metals like arsenic, mercury, cadmium, or manganese. Both meta-analyses suggest that lead exposure is associated with the risk for ADHD. However, because these studies cannot rule out other explanations, one cannot conclude that lead exposure causes ADHD. For example, other work shows that people with ADHD are likely to have lower incomes than those without ADHD.
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