Nationwide population studies: atomoxetine not associated with birth defects

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.

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.”

January 15, 2024

Danish population study: Sex chromosome abnormalities increase risk of ADHD

Danish population study: Sex chromosome abnormalities increase risk of ADHD

Sex chromosome abnormalities are replication errors that produce an atypical number of sex chromosomes relative to the typical 46,XY and 46,XX arrangements.

Sex chromosome abnormalities are replication errors that produce an atypical number of sex chromosomes.  Most people have 23 pairs of chromosomes for a total of 46.  One pair is called the sex chromosome pair.  It is either XX (for biological females) or XY (for biological males).  The term 46,XY refers to a typical biological male and the term 46,XX refers to the typical biological female.  

In rare cases a person may have only 45 chromosomes due to having only one sex chromosome, the X chromosome (45,X).  Some people, rarely, have an extra sex chromosome and are designated: 47,XXX, 47,XXY, and 47,XYY.  These rare sex chromosome differences occur in between 0.5 and 1.3 per 1,000 livebirths. 

These differences have physical manifestations. For example, 45,X is associated with shorter height and abnormal development of the ovaries. The other three are associated with greater height. 47,XXX is associated with premature ovarian failure and 47,XXY with low testosterone.

A Danish and U.S. team used data from Denmark’s single-payer universal health insurance system to assess the association of these sex chromosome differences with the prevalence of ADHD.

They performed a case-cohort study. The source population was all 1,657,449 singleton births in Denmark between May 1, 1981, and Dec 31, 2008. The cases consisted of all 93,608 individuals in this population who were diagnosed with any of five psychiatric disorders, including ADHD. These were compared with a cohort consisting of 50,615 individuals randomly selected from the source population.

The combined population prevalence of these four sex chromosome differences was 1.45 per 1,000. 47,XXY was the most common, at 1.23 per 1,000, followed by 47,XYY at .82 per 1,000, then 47,XXX at .66 per 1,000. 45,X was by far the least common, at less than .23 per 1,000.

All four conditions were associated with significantly increased risk of ADHD:

  • 47,XXY roughly doubled the risk. 
  • 47,XXX increased the risk 2.5-fold.
  • 47,XYY more than quadrupled the risk.
  • 45,X more than sextupled the risk.

These data are intriguing because we know there  are sex differences in the prevalence of ADHD but the causes of those differences are unknown.  

Given that ADHD is more common in boys than girls, one would have predicted that having an extra Y chromosome would increase risk for ADHD.  That is the case here but we also see that having an extra X chromosome also increases risk, which means that the impact of sex chromosomes on ADHD is not straightforward.

January 10, 2023

For Adults with ADHD: What Should you Doctor be Doing for your ADHD?

For Adults with ADHD: What Should Your Doctor be Doing for your ADHD?

Recognizing whether your ADHD is being managed appropriately requires an understanding of what constitutes effective treatment. Here are some indicators of proper ADHD treatment:

Recognizing whether your ADHD is being managed appropriately requires an understanding of what constitutes effective treatment. Here are some indicators of proper ADHD treatment:

Comprehensive Evaluation: An appropriate diagnosis of ADHD involves a comprehensive evaluation, including medical history, clinical interviews, and assessment tools. It should also exclude other conditions that may mimic ADHD.

Clear Communication: Your doctor should provide a clear explanation of ADHD, its symptoms, treatment options, potential side effects, and expected outcomes. They should answer your questions patiently and help dispel any misconceptions.

Individualized Treatment Plan: ADHD treatment often involves a combination of medication, psychotherapy, and lifestyle changes. Your doctor should tailor the treatment plan to your specific needs, symptoms, and life circumstances.

Medication Management: If medication is part of your treatment plan, your doctor should monitor its effects and side effects closely, adjusting the dosage as necessary. Remember, the aim is to maximize benefits and minimize side effects.  Much research shows that it is usually best to start treatment with an FDA approved medication.  If your doctor decides otherwise, you should ask why.

Psychotherapy and Coaching: Pills don’t provide skills.  Many adults with ADHD never acquired life skills due to untreated ADHD. Cognitive-behavioral therapy (CBT) is beneficial for managing ADHD. Your doctor might recommend this and refer you to a psychologist, or they might provide some elements of these services themselves.  

Regular Follow-Ups: Regular follow-ups are critical to assess the effectiveness of the treatment plan and to make necessary adjustments. Your doctor should be tracking your progress and adapting your treatment as needed.

Empowering You: A good doctor will support you in managing your ADHD, providing education, resources, and tools that empower you to lead a healthy, fulfilling life.

Focus on Strengths: ADHD can come with strengths, such as creativity, dynamism, and the ability to think outside the box. An effective healthcare provider will help you leverage these strengths.

Involvement of Loved Ones: Depending on your circumstances, involving your loved ones in your treatment process can be beneficial. They can provide additional support and understanding.

Co-ordinating with Other Healthcare Providers: If you have other healthcare providers involved in your care, your doctor should communicate and coordinate with them to ensure consistent and comprehensive care.

Remember, you have the right to seek a second opinion if you feel your ADHD is not being appropriately managed. Trust your instincts and advocate for your health. It may also be helpful to join ADHD support groups (online or offline) to connect with others who share similar experiences. Their insights and recommendations could be beneficial.  Also keep in mind that achieving an optimal outcome for one’s ADHD often requires the doctor to try a few different medications as it is not currently possible to predict which patients do best on which medications.

January 29, 2024

Parents of Children With ADHD at Higher Risk for Traumatic Injury

Nationwide population study finds higher risk of traumatic injury among parents of children with ADHD

Previous population studies have shown that children with ADHD have a much higher risk of traumatic injuries than their normally developing peers, and that such risk can be greatly reduced with methylphenidate treatment.

But what about the parents of children with ADHD? How does their risk compare with that of parents of normally developing children?

Taiwan has a single-payer public health insurance system that maintains comprehensive healthcare records of virtually every resident.

A Taiwanese research team availed itself of the Taiwan Maternal and Child Health Database, which covers 99.8% of all births, to identify 81,401 fathers and 87,549 mothers who had at least one offspring with ADHD and 1,646,100 fathers and 1,730,941 mothers with no offspring with ADHD.

The team determined children's ADHD status based on either an inpatient diagnosis or four or more  diagnoses.

It looked for parental traumatic injuries including burn injury, fracture, and traumatic brain injury.

To address covariates, it adjusted for age, urbanicity, low-income level, and competing risk of death.

Adjusted for those covariates, parents of children with ADHD were 20% more likely to suffer bone fractures, 27% more likely to have traumatic brain injuries, and 30% more likely to have burn injuries requiring medical treatment than parents of normally developing children.

The elevated risks were significant across the board, but roughly twice as much s for mothers as for fathers of children with ADHD - up 30% vs 15% for bone fractures, up 35% vs 23% for burn injuries, and up 45% vs 21% for traumatic brain injuries.

The authors noted that ADHD is highly heritable and that the findings may in part point to undiagnosed adult ADHD.

Another contributing factor, they suggested, is that "studies have revealed that a high proportion of parents having children with ADHD experience depression and anxiety. Stress-related negative emotions (depression and anxiety) were shown to cause loss of concentration, thereby increasing the likelihood of accidental events such as traffic accidents and contributing to the increased risks of traumatic injury among parents of children  ADHD."

The much-higher elevated risk for mothers seems to support this hypothesis, because mothers continue to be the principal caregivers in Taiwan, and are thus more exposed to the behaviors of their children. The authors cited a study indicating that "diagnosis of ADHD for children was reported to be a predictor of increased caregiver burden."

They concluded, "Given that knowledge is fundamental to act, it is essential to educate the parents of children with ADHD on the increased risk of traumatic injuries they may have. ... The need for behavioral and pharmacological intervention in parents of children with ADHD should be evaluated, especially in the parents with undiagnosed ADHD or sub-threshold ADHD symptoms. It deserves further prospective studies with longer follow-up periods to explore whether undiagnosed ADHD, care burden of parents, and children's aggressive behaviors contribute to the increased risks of traumatic injuries in parents of children with ADHD."

December 7, 2023

Meta-analysis Finds "Parent-Training" Helpful in Raising Children with ADHD

Meta-analysis finds behavioral parent training broadly helpful in raising children with ADHD

The aim of behavioral parent training is to improve the child's behavior through improved parenting. Noting that "it is unknown which of its components are most effective," a Dutch team of researchers conducted a systematic search of the peer-reviewed medical literature to identify randomized controlled trials (RCTs) suitable for meta-analysis.

Twenty-nine RCTs with a combined total of 2,345 participants met the criteria.

The team explored five types of outcome variables:

·        Positive parenting: behaviors such as reinforcement, monitoring, stimulating, and guiding the child.
·        Negative parenting: behaviors such as corporal punishment, harsh discipline, inconsistent parenting, and poor monitoring.
·        Parenting sense of competence: the extent to which parents perceive themselves as competent or effective in raising their child.
·        Quality of the parent-child relationship: signs of affection, support, sensitivity, and responsiveness.
and behavioral parent training aims:
·        Parental mental health: measures included parenting stress and several indices of parental psychopathologies, such as depression and anxiety.

A meta-analysis of 19 RCTs with 1,070 participants found a medium effect size improvement in positive parenting. Evidence of publication bias was borderline, but a trim-and-fill adjustment still reported a medium effect size reduction in ADHD symptoms. Similarly, limiting the meta-analysis to the 12 RCTs that were probably blinded made no difference in the outcome.

A second meta-analysis, of 15 RCTs with 878 participants, found a small-to-medium effect size reduction in negative parenting, after adjusting for publication bias. Limiting the meta-analysis to the six RCTs that were probably blinded modestly increased the effect size.

After adjusting for publication bias, a meta-analysis of 13RCTs with a combined total of 783 participants reported a small-to-medium effect size improvement in the quality of parent-child relationships. Limiting the meta-analysis to the six RCTs that were probably blinded made no difference in the outcome.

After adjusting for publication bias, a meta-analysis of 17 RCTs with a combined total of 1,083 participants reported a medium effect size improvement in parent sense of competency.

Finally, with no sign of publication bias, 23 RCTs with a combined total of 1,191 participants found a small-to-medium effect size improvement in parental mental health.

The team concluded, "Parent training had robust small- medium-sized positive effects on all parental outcomes relative to control conditions, both for unblinded and probably blinded measures. ... A reassuring finding was that effect sizes on positive parenting, negative parenting, and the parent-child relationship did not differ between probably blinded and unblinded measures, indicating that effects are not merely attributable to parents' investment affecting their assessment of outcome measures."

October 26, 2023

Does ADHD Medication Improve the Parenting Skills of Adults with ADHD?

Does ADHD Medication Improve the Parenting Skills of Adults with ADHD?

Raising children is not easy. I should know.

As a clinical psychologist, I've helped parents learn the skills they need to be better parents. And my experience raising three children confirmed my clinical experience.

Parenting is a tough job under the best of circumstances, but it is even harder if the parent has ADHD.

For example, an effective parent establishes rules and enforces them systematically. This requires attention to detail, self-control, and good organizational skills. Given these requirements, it is easy to see how ADHD symptoms interfere with parenting. These observations have led some of my colleagues to test the theory that treating ADHD adults with medication would improve their parenting skills. I know about two studies that tested this idea.

In 2008, Dr. Chronis-Toscano and colleagues published a study using a sustained-release form of methylphenidate for mothers with ADHD. As expected, the medication decreased their symptoms of inattention and hyperactivity/impulsivity. The medication also reduced the mother's use of inconsistent discipline and corporal punishment and improved their monitoring and supervision of their children.

In a 2014 study, Waxmonsky and colleagues observed ADHD adults and their children in a laboratory setting once when the adults were off medication and once when they were on medication. They used the same sustained-release form of amphetamine for all the patients. As expected, the medications reduced ADHD symptoms in the parents. This laboratory study is especially informative because the researchers made objective ratings of parent-child interactions, rather than relying on the parents' reports of those interactions. Twenty parents completed the study. The medication led to less negative talk and commands and more praise by parents. It also reduced negative and inappropriate behaviors in their children.

Both studies suggest that treating ADHD adults with medication will improve their parenting skills. That is good news. But they also found that not all parenting behaviors improved. That makes sense. Parenting is a skill that must be learned. Because ADHD interferes with learning, parents with the disorder need time to learn these skills. Medication can eliminate some of the worst behaviors, but doctors should also provide adjunct behavioral or cognitive-behavioral therapies that could help ADHD parents learn parenting skills and achieve their full potential as parents.

May 7, 2021