The rise in autism prevalence. Non-stimulant medications for ADHD. Shared reading effects on social-emotional development.
Welcome to the final installment of DBP in 1-2-3 of 2021! This newsletter is a little over a year old now. Thank you to everyone who reached out to me for words of support and appreciation. I am so happy this newsletter has been valuable and enjoyable to read.
I look forward to keeping this going for the foreseeable future. Please contact me if you have ideas for topics. So much of what is going on in the world today is relevant to developmental-behavioral pediatrics and child health.
1. The rise in autism prevalence
This year the CDC published the latest prevalence rate of 8-year-old children with an autism spectrum disorder in the United States, increasing from 1 in 54 to 1 in 48. It has steadily risen over the last 50 years; at the turn of the century, it was 1 in 150. This rate is an alarming trend at first glance. Why are there so many more children with autism? Context is important here. These studies published by the CDC cannot completely rule out environmental factors (though it is pretty safe to presume that immunizations do not cause autism). However, we can point to a few phenomena to help us understand this rise in autism: improved public awareness, expanded diagnostic criteria, and heightened screening in early childhood.
National organizations such as Autism Speaks and the CDC have made inroads in educating the public about autism. They have helped reduce stigma and dispel many misconceptions. However, we should not ignore the influence of social media and other informal outlets. Many vocal families within the autism community are doing excellent work advocating for children with ASD.
The publication of The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) in 2013 was a significant update on the diagnostic criteria for autism. The diagnosis of Autism Spectrum Disorder (ASD) was added to encompass individuals on the higher functioning end of the spectrum. Many of these individuals used to have other related but separate diagnoses like Asperger syndrome or PDD-NOS (pervasive developmental disorder, not otherwise specified). The DSM-5 made the diagnostic process more straightforward. Still, perhaps the primary intention of eliminating those diagnoses and widening the autism umbrella was so more children could qualify for school-based services and therapeutic interventions. In large part, this has been successful. School districts recognize autism as an eligible condition for an Individualized Education Program (IEP). In addition, most health insurance companies today will not authorize therapies like speech-language and applied behavioral analysis (ABA) without a medical diagnosis of autism.
Thanks to efforts by leading pediatric organizations like the American Academy of Pediatrics, developmental screening for delays and autism is now standard at all primary care well-child visits from 9 to 30 months of age. This has resulted in earlier identification and evaluations for developmental delay (and therefore more diagnoses). One important outcome from the most recent CDC report was that nearly half of these 8-year-olds were evaluated for autism by 36 months of age, a 44% increase from two years prior.
The diagnosis of autism also appears to be made earlier in childhood. The CDC reported that in children born in 2014, the diagnosis of autism by age 4 years was 50% higher than children born in 2010. There was also an increased rate of ASD diagnosis in ethnic and racial minority children and children living in lower-income neighborhoods suggesting an improvement in screening and evaluation.
It is important to note from the 2010 birth cohort that about a third with a diagnosis of ASD had a coexisting intellectual disability (IQ ≤ 70). The median age of diagnosis was earlier than children without an intellectual disability. While this is a good indication that we recognize autism in the more severe cases, many children with milder symptoms are flying under the radar. For example, boys are still about four times more likely to have an ASD diagnosis than girls. Experts argue that this may be explained by some of the phenotypic differences between boys and girls with autism. Girls generally have more subtle or difficult to recognize symptoms, something I can personally attest to in my practice.
The CDC’s findings are based on its Autism and Developmental Disabilities Monitoring Network, which spans 11 sites/states. While this is not fully representative of the United States, it is a diverse enough swath of our country to be a reliable indicator of the prevalence of autism. And what’s interesting in reading the report in more detail is that there are significant differences in detection rates between sites.
The take-home message for all of this is that anxious families may bring this prevalence rate up to you during an encounter along with wild theories or conspiracies they have gleaned from unreliable but “trusted” sources. While the book on autism is far from complete, we know much more than we did 25 years ago. Our heightened awareness, greater public acceptance, improved screening workflows, and the use of broadened diagnostic criteria are significant factors to consider in the explanation of this increased rate.
2. Non-stimulant medications for ADHD
Stimulant medications are considered first-line for the pharmacological treatment of ADHD with a strong evidence base and high efficacy rate (about 70%). Yet, there are some children where stimulants are just a poor fit, whether due to adverse side effects or ineffective outcomes. There is also a social stigma attached to stimulants. Even though it is unjustified, it is hard for some families to shake what they hear or read on social media, from friends and family, or the lay press. Non-stimulants in these instances may make the most sense and are worth suggesting to families.
I won’t get into the nitty-gritty behind non-stimulant medications for ADHD. There are excellent resources out there if interested in a deeper dive (e.g., UpToDate, Pediatric Psychopharmacology for Primary Care). Here, I’ll give a brief overview of three common non-stimulants, along with a few pearls to consider. It is important to start on a low dose and closely monitor for adverse side effects. Unlike stimulants, non-stimulants are more weight-based with dosing, take a while before therapeutic effects are seen, and generally have a longer duration of action. These medications are also not controlled substances.
Guanfacine/Clonidine
Alpha agonist medications were initially developed to treat hypertension but serendipitously found to help calm a person’s “fight-or-flight” response. Perhaps it is the most commonly prescribed nonstimulant for ADHD, especially in younger children. It is FDA approved for ADHD in individuals 6-years and over, but not unusual to see a 5-year-old on one. They are generally well-tolerated in children; a common reason for stopping is because it is ineffective. Clonidine typically has more sedating properties than guanfacine because it acts on several alpha-receptors. It is why it is preferred over guanfacine to treat insomnia (though not recommended as a long-term solution for most children). Alpha agonists, in general, are more helpful for targeting disruptive externalizing behaviors like aggression, hyperactivity, and impulsivity than attention/focus and other executive functioning problems. Immediate-release (IR) versions work for 4-8 hours, and some children need to take it 2-3 times a day to get sustained effects throughout the day. The extended-release (ER) version is taken once daily and lasts up to 24 hours.
Pearls to consider:
The biggest barrier to starting the ER version is that it cannot be crushed and must be swallowed whole. There are no liquid/chewable/dissolvable equivalents.
Hypotension is an uncommon but plausible side effect that is more likely seen in IR formulations. Rebound hypertension can occur if an alpha agonist is abruptly stopped. It is a rare scenario that is more likely to occur at higher doses and if the child has been on it continuously for an extended period (many months). Due to such concerns, it is recommended to wean children off an alpha agonist by increments of 1 mg (for guanfacine) or 0.1 mg (for clonidine) every 3-7 days.
Sedation is by far the most common side effect, but this goes away after 1-3 weeks of their bodies adjusting to the medication for most children.
Think side effects from an alpha agonist if there are sudden daytime accidents (enuresis). It is a rare side effect, but I’ve seen it enough times in my practice to bring it up when discussing the potential side effects of alpha agonists.
Works synergistically with stimulants for some children (counteracts the rebound effects as stimulants wear off or helps with self-regulation during and in between stimulant doses).
Atomoxetine
This selective norepinephrine reuptake inhibitor is FDA approved for ADHD. Although efficacy is lower than stimulants, it seems more effective with inattention symptoms than alpha agonists. The advantage of atomoxetine is that it generally works all day with once-daily dosing (some children benefit from twice-daily dosing) and does not usually suppress appetite or delay sleep onset (though it can cause GI symptoms and sedation). Like stimulants, caution and consultation with a cardiologist are needed if the child has or is at high risk for cardiac disease. In addition, atomoxetine has a black boxed warning for increased suicidal ideation. However, this is a rare adverse effect, and further analysis of longitudinal data showed that atomoxetine was not associated with suicide or suicide attempts.
Dosing in children is weight dependent, typically starting at 0.5 mg/kg up to a daily dose of 1.2 mg/kg with a max daily dose not greater than 1.4 mg/kg or 100 mg/day, whichever is less.
Pearls to consider:
Full therapeutic effects are not achieved until 4-6 weeks of starting, so families need to have that expectation to prevent premature discontinuation of treatment. This is a disadvantage compared to stimulant medications, which work almost instantaneously.
Once therapeutic effects are achieved, it is continuous (round-the-clock). This is a significant advantage of atomoxetine when compared to stimulants.
When stopping atomoxetine, there is no need for a wean.
Atomoxetine capsules must be swallowed whole. They cannot be opened and mixed with food or drink. There are no liquid or chewable forms. A new selective norepinephrine reuptake inhibitor called viloxazine (trade name Qelbree) was released earlier this year. Technically, it should work the same as atomoxetine with one significant difference: the capsules can be opened and their contents mixed with food.
Although not FDA-approved for anxiety, atomoxetine has some anxiolytic properties. SSRIs are still preferable as a first-line drug to treat anxiety disorders, but atomoxetine might be something you consider first with a patient with ADHD and mild coexisting anxiety.
Bupropion
Classified as an atypical antidepressant with stimulant properties because it blocks the reuptake of norepinephrine and dopamine. It is used off-label to treat ADHD and is considered in children with coexisting depression. Like SSRIs and atomoxetine, bupropion also has a black boxed warning for suicidal ideation. Cardiac evaluation is recommended in a child with preexisting cardiac disease or considered high-risk.
Pearls to consider:
Not recommended as the first-choice medication for pediatric ADHD given the known efficacy for FDA-approved ADHD medications. If stimulants are not an option, go with atomoxetine or guanfacine first.
It can be activating and exacerbate anxiety and panic attacks in some patients. I would hesitate to start this medication in a child with a coexisting anxiety disorder.
The ER versions cannot be crushed, chewed, or divided. The IR formulation lasts 4-6 hours and therefore needs to be taken 2-3 times per day for sustained effects.
There is a dose-related risk for seizures and generally not recommended in children at-risk for seizures or who have a history of seizures.
Despite its status as a third-tier drug for ADHD, I have seen bupropion work wonders in my adolescent patients with coexisting depression who did not tolerate more conventional ADHD medications.
3. Shared reading effects on social-emotional development
We all intuitively know that reading to young children is a good thing. Good for cognitive and language development. Good for early literacy and school readiness. Good for relationships and attachment. Not surprisingly, much scientific research supports these benefits of shared reading (reading between caregiver and child). However, the link between shared reading and social-emotional development has not been explored closely until recently. The American Academy of Pediatrics recommends the surveillance of social-emotional development and shared reading in primary care. Many pediatric practices now offer early literacy programs like Reach Out and Read and routinely screen for social-emotional delays in young children using validated tools like the Ages and Stages: Social Emotional Questionnaire (ASQ:SE) or the Survey of Well-being of Young Children (SWYC).
In a retrospective review of longitudinal data from the electronic medical record of a large primary care setting at Cincinnati Children’s Hospital (n = 5693), Martin, et al looked at the association between shared reading and social-emotional development. They found that less shared reading was associated with more social-emotional problems in patients aged 30-66 months. They came to this conclusion through analyzing scores on the ASQ:SE and documentation of caregiver responses to the question: “How often did you and other family members read stories or look at books with your child in the past week?” Response options were “Most (5–7) days of the week,” “Some (2–4) days of the week,” or “Rarely have time (0–1 days of the week).” This association held steady even after adjusting for child sex, age of visit, food or housing insecurity, and caregiver depression.
While it is important to note that this study reports only an association, not a causation, it supports the idea that shared reading is more than just an exercise in promoting literacy or cognitive development in young children. It also appears to be an important activity in promoting social communication skills, healthy emotional regulation, and positive caregiver-child relationships. Imagine all the oxytocin and dopamine released in the brain during storytime! There are, of course, many other caregiver-child activities that do these things, but reading is perhaps in the best position to accomplish them all at once.
This paper reminds me of the “5 Rs” of early education: Reading (as a fun, bonding activity with family), Rhyming (through reading, songs, play, and conversations), Routines (to help children understand expectations), Rewards (including praise, for everyday successes, small or large), and Relationships (when they are bidirectional, meaningful, nurturing, and sustained). I would add a fourth R, Relaxation. I am concerned about children’s days being over-scheduled or too structured. Children need free time to play and explore at their own pace. They need to learn how to deal with boredom. There seem to be fewer opportunities to relax our minds in our modern, online-all-the-time digital heavy lives. This certainly has implications for a child’s social-emotional well-being. So, as we close out 2021, keep these R’s in mind with your families as we enter a new year against the backdrop of a lingering pandemic.