January 15, 2024

Nationwide population studies: atomoxetine not associated with birth defects

Treatment for ADHD among women of reproductive age is increasingly common. 

That means we need to know whether ADHD medications have any tendency to increase the risk of birth defects. Previous studies have looked mostly at ADHD medications that are central nervous system stimulants, especially methylphenidate and amphetamines.

Atomoxetine is the most widely prescribed non-stimulant for treating ADHD. It acts indirectly, by selectively inhibiting the removal of norepinephrine, a neurotransmitter that mobilizes the brain and body for action. 

To explore whether atomoxetine might be associated with any higher risk of birth defects, an international study team examined nationwide population data from four Nordic countries with universal single-payer health insurance systems – Denmark, Norway, Sweden, and Iceland – along with nationwide data from the U.S. Medicaid system, which is likewise single-payer, and covers roughly half of all births in the U.S.

They compared the prevalence of major birth defects among infants born to women exposed to atomoxetine in the first trimester (three months) of pregnancy to the prevalence among infants born to women not exposed to any ADHD drug during the period beginning three months before their last menstrual period and concluding at the end of the first trimester.

The team adjusted for maternal characteristics such as maternal age, calendar year of delivery, childbirth and medical characteristics, psychiatric conditions, high blood pressure, diabetes, kidney disease, obesity, and smoking.

In more than 2.4 million births in the four Nordic countries, and almost 1.8 million births in the U.S., there was absolutely no sign of increased prevalence of major infant malformations among infants born to mothers taking atomoxetine. 

More specifically looking at heart defects, there was again no significant association with maternal atomoxetine use, either in the Nordic population, the U.S. population, or the combined populations.

For limb malformations, there was again no significant association between maternal atomoxetine use and birth defects in the combined populations. There was an appearance of a significant association in the Nordic population, but that was based on only 5 instances, and because there were zero instances in the U.S. population, there was no net association at all in the combined population of more than 4.2 million.

The team concluded, “We found no increased prevalence of major congenital malformations overall associated with atomoxetine use in early pregnancy. The increased prevalence of limb malformations in the Nordic countries was not observed in the US. … Given the low absolute risk of both of these outcomes, these results are reassuring from a public health perspective and provide important information in the consideration of whether to continue treatment with atomoxetine during pregnancy.”

Gabriella Bröms, Sonia Hernandez-Diaz, Krista F. Huybrechts, Brian T. Bateman, Eskild Bendix Kristiansen, Kristjana Einarsdóttir, Anders Engeland, Kari Furu, Mika Gissler, Pär Karlsson, Kari Klungsøyr, Anna-Maria Lahesmaa-Korpinen, Helen Mogun, Mette Nørgaard, Johan Reutfors, Henrik Toft Sørensen, Helga Zoega, MA, and Helle Kieler, “Atomoxetine in Early Pregnancy and the Prevalence of Major Congenital Malformations: A Multinational Study,” Journal of Clinical Psychiatry (2023) 84(1): 22m14430, https://doi.org/10.4088/JCP.22m14430.

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Swedish nationwide population study identifies top predictors of ADHD diagnoses among preschoolers

Most preschool-aged children diagnosed with ADHD also exhibit comorbid mental or developmental conditions. Long-term studies following these children into adulthood have demonstrated that higher severity of ADHD symptoms in early childhood is associated with a more persistent course of ADHD. 

The Study: 

Sweden has a single-payer national health insurance system that covers virtually all residents, facilitating nationwide population studies. An international study team (US, Brazil, Sweden) searched national registers for predictors of ADHD diagnoses among all 631,695 surviving and non-emigrating preschoolers born from 2001 through 2007.  

Preschool ADHD was defined by diagnosis or prescription of ADHD medications issued to toddlers aged three through five years old.  

Predictors were conditions diagnosed prior to the ADHD diagnosis. 

A total of 1,686 (2.7%) preschoolers were diagnosed with ADHD, with the mean age at diagnosis being 4.6 years. 

The Numbers:

Adjusting for sex and birth year, the team reported the following predictors, in order of magnitude: 

  • Previous diagnosis of autism spectrum disorder increased subsequent likelihood of ADHD diagnosis twentyfold. 
  • Previous diagnosis of intellectual disability increased subsequent likelihood of ADHD diagnosis fifteenfold. 
  • Previous diagnosis of speech/language developmental disorders and learning disorders, as well as motor and tic disorders, increased subsequent likelihood of ADHD diagnosis thirteen-fold. 
  • Previous diagnosis of sleep disorders increased subsequent likelihood of ADHD diagnosis fivefold. 
  • Previous diagnosis of feeding and eating disorders increased subsequent likelihood of ADHD diagnosis almost fourfold. 
  • Previous diagnosis of gastroesophageal reflux disease (GERD) increased subsequent likelihood of ADHD diagnosis 3.5-fold. 
  • Previous diagnosis of asthma increased subsequent likelihood of ADHD diagnosis 2.4-fold. 
  • Previous diagnosis of allergic rhinitis increased subsequent likelihood of ADHD diagnosis by 70%. 
  • Previous diagnosis of atopic dermatitis or unintentional injuries increased subsequent likelihood of ADHD diagnosis by 50%. 

The Conclusion: 

This large population study underscores that many conditions present in early childhood can help predict an ADHD diagnosis in preschoolers. Recognizing these risk factors early may aid in identifying and addressing ADHD sooner, hopefully improving outcomes for children as they grow

July 2, 2025

Northern Finnish Population Study Finds ADHD Slashes Higher Education Attainment, Comorbidity of ADHD + ODD much worse

Background:

Although ADHD typically begins in childhood, its symptoms frequently continue into adulthood, and it is widely acknowledged as having a lifelong prevalence for most persons with ADHD. 

ADHD symptoms are linked to poor academic performance, mainly due to cognitive issues like compromised working memory. These symptoms lead to long-term negative academic outcomes and difficulty in achieving higher educational degrees. 

Oppositional Defiant Disorder (ODD) often co-occurs with ADHD. In community samples, it appears in about 50–60% of those with ADHD. ODD symptoms include an angry or irritable mood, vindictiveness toward others, and argumentative or defiant behavior that lasts more than 6 months and significantly disrupts daily life.  

Since ODD tends to co-occur with ADHD, research on pure ODD groups without ADHD is limited, especially in community samples. This longitudinal study aimed to examine the impact of ADHD and ODD symptoms in adolescence on academic performance at age 16 and educational attainment by age 32. 

Study:

Finland, like other Nordic countries, has a single-payer health insurance system that includes virtually all residents. A Finnish research team used the Northern Finnish Birth Cohort to include all 9,432 children born from July 1, 1985, through June 30, 1986, and followed since then. 

ADHD symptoms were measured at age 16 using the Strengths and Weaknesses of ADHD symptoms and Normal-behaviors (SWAN) scale. 

Symptoms of ODD were screened using a 7-point rating scale similar to the SWAN scale, based on eight DSM-IV-TR criteria: “Control temper”, “Avoid arguing with adults”, “Follow adult requests or rules”, “Avoid deliberately annoying others”, “Assume responsibility for mistakes or misbehaviour”, “Ignore annoyances from others”, “Control anger and resentment”, and “Control spitefulness and vindictiveness.” 

Higher education attainments were determined at age 32. 

Results:

After adjusting for the educational attainments of the parents of the subjects, family type, and psychiatric disorders other than ADHD or ODD, males with ADHD symptoms at age 16 had a quarter, and females a little over a third, of the higher education attainments of peers without ADHD symptoms at age 32.  

With the same adjustments, males with ODD symptoms alone had two-thirds, and females 80%, of the higher education attainments of peers without ODD, but neither outcome was statistically significant. 

However, all participants with combined ADHD and ODD symptoms at age 16 had roughly one-fifth of the higher education attainments of peers without such symptoms upon reaching age 32. 

Interpretation: 

The team concluded, “The findings that emerged from this large longitudinal birth cohort study showed that the co-occurrence of ODD and ADHD symptoms in adolescence predicted the greatest deficits of all in educational attainment in adulthood.” 

This study highlights the significant, long-lasting impact that co-occurring ADHD and ODD symptoms can have on educational outcomes well into adulthood. It underscores the importance of addressing both disorders together during adolescence to help improve future academic success.

July 1, 2025

U.S. Nationwide Study Finds Down Syndrome Associated with 70% Greater Odds of ADHD

The Background:

Down syndrome (DS) is a genetic disorder resulting from an extra copy of chromosome 21. It is associated with intellectual disability. 

Three to five thousand children are born with Down syndrome each year. They have higher risks for conditions like hypothyroidism, sleep apnea, epilepsy, sensory issues, infections, and autoimmune diseases. Research on ADHD in patients with Down syndrome has been inconclusive. 

The Study:

The National Health Interview Survey (NHIS) is a household survey conducted by the National Center for Health Statistics at the CDC. 

Due to the low prevalence of Down syndrome, a Chinese research team used NHIS records from 1997 to 2018 to analyze data from 214,300 children aged 3 to 17, to obtain a sufficiently large and nationally representative sample to investigate any potential association with ADHD. 

DS and ADHD were identified by asking, “Has a doctor or health professional ever diagnosed your child with Down syndrome, Attention Deficit Hyperactivity Disorder (ADHD), or Attention Deficit Disorder (ADD)?” 

After adjusting for age, sex, and race/ethnicity, plus family highest education level, family income-to-poverty ratio, and geographic region, children and adolescents with Down syndrome had 70% greater odds of also having ADHD than children and adolescents without Down syndrome. There were no significant differences between males and females. 

The Take-Away:

The team concluded, “in a nationwide population-based study of U.S. children, we found that a Down syndrome diagnosis was associated with a higher prevalence of ASD and ADHD. Our findings highlight the necessity of conducting early and routine screenings for ASD and ADHD in children with Down syndrome within clinical settings to improve the effectiveness of interventions.” 

June 27, 2025