March 5, 2022

Comedication with ADHD medication in adults in a nationwide population cohort study

Persons with ADHD have known to have high rates of psychiatric comorbidities. There is also growing evidence of somatic (non-psychiatric) comorbid disorders among youths with ADHD, such as metabolic syndrome (which can lead to type 2 diabetes) and chronic inflammation (such as asthma and allergic rhinitis). Much less is known, however, about comorbid conditions in adults with ADHD.

An international team of researchers looked for indicators of comorbid conditions in a nationwide cohort study using Swedish national registers. The target population was Swedish residents between the ages of 18 and 64 in 2013 and more specifically those who had been prescribed ADHD medication. They identified over 41,000 individuals who met these criteria, including over twenty thousand young adults aged 18-29 years, over sixteen thousand middle-aged adults aged 30-49 years, and over four thousand older adults aged 50-64. The remainder of the overall cohort were used as controls.

Young adults receiving ADHD medications were four times as likely to also be receiving somatic medications, and older adults were seven times as likely. The highest rate of co-medication -roughly five times more frequent than among controls - was for respiratory system medications. The second most common was for alimentary tract and metabolic system medications, with odds over four times higher than for controls. Cardiovascular system medications were the next most common, with odds among young adults receiving ADHD medications over four times those of controls, though reducing with age to being twice as common in older adults with ADHD. Patterns were similar among men and women.

Adults receiving ADHD medications were far more likely to also be receiving other psychotropic medications. Middle-aged adults were 21 times as likely to be dispensed such medications as controls, older adults eighteen times more likely, and younger adults fifteen times more likely.

For young adults prescribed ADHD medications, the most prevalent co-prescriptions were for addictive disorders, which were dispensed at over 26 times the rate for controls. For middle-aged and older adults, on the other hand, the most prevalent co-prescriptions were for antipsychotics, which were likewise dispensed at over 26 times the rate for controls. Results remained consistent for individuals who had an ADHD diagnosis in addition to an ADHD prescription.

In addition, individuals receiving ADHD medications were also on average taking more types of prescriptions, rising from 2.5 classes of medications at age 18 to five classes at age 64. For controls, the equivalent numbers were 0.9 types of medications at age 18, rising to 2.7 at age 64.

Looking at specific somatic medications prescribed, those for respiratory conditions were ones typically prescribed for asthma and allergic reactions, reinforcing a previously known association. Insulin preparations also had high rates of co-prescription, again further confirming the known association with obesity and diabetes.

On the other hand, the most commonly dispensed alimentary tract and metabolic system medications included proton pump inhibitors, typically prescribed for gastric/duodenal ulcers and gastroesophageal reflux disease. Sodium fluoride, prescribed to prevent dental caries, was also prominent. Neither of these is an established association and warrants further exploration.

Turning to psychotropic medications, the most frequent prescriptions were with drugs used to treat addictive disorders and with antipsychotics. Rates of opioid co-prescription were also notably high, a source of concern given the higher proclivity of persons with ADHD to substance use disorders.

Le Zhang, AndreasReif, Ebba Du Rietz, Tyra Lagerberg, Agnieszka Butwicka, Brian M. D'Onofrio, Kristina Johnell, Nancy L. Pedersen, Henrik Larsson, and Zheng Chang, "Comedicationand Polypharmacy With ADHD Medications in Adults: A Swedish Nationwide Study," Journal of Attention Disorders (2020),https://doi.org/10.1177/1087054720923725.

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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

Meta-analyses Find Dose-response Association Between Lead Exposure and Subsequent ADHD

Meta-analyses Find Dose-response Association Between Lead Exposure and Subsequent ADHD

Background:

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.

Methods:

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.

Key Findings:
  1. Lead Exposure and ADHD:some text
    • A meta-analysis of 22 studies with over 20,000 participants found that early exposure to lead was linked to about twice the odds of an ADHD diagnosis compared to unexposed children.
    • However, results varied widely among studies, and signs of publication bias were detected. After adjusting for this bias, the increased odds dropped to about 50%.
    • A dose-response relationship was found:some text
      • Blood lead levels of 2.5 µg/dL increased ADHD risk by 1.8 times.
      • Levels of 5 µg/dL increased the risk 2.5 times.
      • Levels of 7.5 µg/dL increased the risk 2.75 times.
      • Levels of 10 µg/dL tripled the risk.
  2. Other Metals:some text
    • No significant links were found between ADHD and exposure to arsenic, mercury, cadmium, or manganese. Fewer studies were available for these metals, and participant numbers were much smaller:some text
      • Arsenic exposure: 25% higher odds of ADHD (4 studies, 3,116 participants).
      • Mercury exposure: 25% higher odds (6 studies, 2,916 participants).
      • Cadmium exposure: 25% higher odds (5 studies, 2,419 participants).
      • Manganese exposure: 45% higher odds (6 studies, 1,664 participants).
  3. Austrian Study: An Austrian team (Rosenauer et al., 2024) also conducted a meta-analysis on lead exposure and ADHD. They included 14 studies with over 7,600 participants and found:some text
    • Lead exposure increased the odds of ADHD by about 25%.
    • Studies focusing on higher lead levels found a 43% increased risk, supporting a dose-response relationship.
    • Study results were consistent, with no signs of publication bias.
Conclusion:

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.  

January 17, 2025