May 17, 2021
There are several very effective drugs for ADHD, and those treatment guidelines from professional organizations view these drugs as the first line of treatment for people with ADHD. The only exception is for preschool children where medication is only the first line of treatment for severe ADHD; the guidelines recommend that other preschoolers with ADHD be treated with non-pharmacologic treatments, when available. Despite these guidelines, some parents and patients have been persuaded by the media or the Internet that ADHD drugs are dangerous and that non-drug alternative are as good or even better. Parents and patients may also be influenced by media reports that doctors overprescribe ADHD drugs or that these drugs have serious side effects. Such reports typically simplify and/or exaggerate results from the scientific literature. Thus, many patients and parents of ADHD children are seeking non-drug treatments for ADHD. What are these non-pharmacologic treatments and do they work? My next series of blogs will discuss each of these treatments in detail. Here I'll give an overview of my evidenced-based taxonomy of non-pharmacologic treatments for ADHD described in more detail in a book I recently edited (Faraone, S. V. &Antshel, K. M. (2014). ADHD: Non-Pharmacologic Interventions. Child Adolesc Psychiatry Clin N Am 23, xiii-xiv.). I use the term "evidence-based" in the strict sense applied by the Oxford Center for Evidenced Based Medicine (OCEBM; http://www.cebm.net/). Most of the non-drug treatments for ADHD fall into three categories: behavioral, dietary, and neurocognitive. Behavioral interventions include training parents to optimize methods of reward and punishment for their ADHD child, teaching ADHD children social skills, and helping teachers apply principles of behavior management in their classrooms. Cognitive behavior therapy is a method that teaches behavioral and cognitive skills to adolescent and adult ADHD patients. Dietary interventions include special diets that exclude food coloring or eliminate foods believed to cause ADHD symptoms. Other dietary interventions provide supplements such as iron, zinc, or omega-3 fatty acids. The neurocognitive interventions typically use a computer-based learning setup to teach ADHD patients cognitive skills that will help reduce ADHD symptoms. There are two metrics to consider when thinking about the evidence base for these methods. The first is the quality of the evidence. For example, a study of 10 patients with no control group would be a low-quality study, but a study of 100 patients randomized to either a treatment or control group would be of high quality and the quality would be even higher if the people's rating patient outcomes did not know who was in each group. The second metric is the magnitude of the treatment effect. Does the treatment dramatically reduce ADHD symptoms, or does it have only a small effect? This metric is only available for high-quality studies that compare people treated with the method and people treated with a 'control' method that is not expected to affect ADHD. I used a statistical metric to quantify the magnitude of the effect. Zero means no effect, and larger numbers indicate better effects on treating ADHD symptoms. For comparison, the effect of stimulant drugs for ADHD is about 0.9, which is derived from a very strong evidence base. The effects of dietary treatments are smaller, about 0.4 to 0.5, but because the quality of the evidence is not strong, these results are not certain and the studies of food color exclusions apply primarily to children who have high intakes of such colorants. In contrast to the dietary studies, the evidence base for behavioral treatments is excellent, but the effects of these treatments on ADHD symptoms are very small, less than 0.1. Supplementation with omega-3 fatty acids also has a strong evidence base, but the magnitude of the effect is also small (0.1 to 0.2). The neurocognitive treatments have modest effects on ADHD symptoms (0.2 to 0.4) but their evidence base is weak. This review of non-drug treatments explains why ADHD drug treatments are usually used first. The evidence base is stronger, and they are more effective in reducing ADHD symptoms. There is, however, a role for some non-drug treatments. I'll be discussing that in subsequent blog posts. See more evidence-based information about ADHD at www.adhdinadults.com
Faraone, S. V.&Antshel, K. M. (2014). ADHD: Non-Pharmacologic Interventions. ChildAdolescPsychiatr Clin N Am 23, xiii-xiv.
Faraone, S. V. &Antshel, K. M. (2014).Towards an evidence-based taxonomy of nonpharmacologic treatments for ADHD.Child AdolescPsychiatr Clin N Am 23, 965-72.
Maternal infections and inflammatory responses during pregnancy have been proposed as risk factors for neurodevelopmental disorders such as ADHD.
Taiwan has a single-payer health insurance system that covers virtually the entirety of its population. Its Ministry of Health and Welfare maintains the National Health Insurance Research Database (NHIRD), with detailed information on outpatient services, hospitalizations, and medical treatment for nearly 99% of all residents.
A Taiwanese study team used NHIRD to examine to examine the relationship between maternal hospitalization for infection, and early childhood infection, and subsequent ADHD in offspring. The study cohort originated with all 3,260,879 individuals born between 2001 and 2018.
The team excluded births from foreign mothers, still births, births with congenital defects, low birth weights, abnormally late births, twins, triplets, and other multiple births, culminating in a final population cohort of 2,885,662 live-born single infants across 1,893,171 families, and 1,864,660 individuals with full siblings from 872,169 families comprising the full sibling cohort.
Study participants were followed until diagnosis of a neurodevelopmental disorder, their death, or the end of 2021.
After adjusting for sex, birth year, paternal and maternal ages, birthweight, birth season, parity, delivery method, 1 minute APGAR score (evaluating baby’s appearance, pulse, grimace, activity and respiration at birth), gestational age, pregnancy and delivery complications, parental history of neurodevelopmental disorders, maternal asthma and diabetes, urbanization level of the residential area, and family’s insurance amount, offspring of mothers hospitalized for infections had 14% greater odds of being subsequently diagnosed with ADHD.
However, in the full sibling cohort of over 1.8 million, this association vanished. That held true for each of the three trimesters of pregnancy. It also held true for bacterial infections. Surprisingly, offspring of mothers hospitalized for viral infections were 24% less likely to be diagnosed with ADHD than their siblings not exposed to maternal viral infection. Because of that, they also had a 6% lower risk overall.
After the same adjustments, early childhood infection was associated with 16% greater odds of being diagnosed with ADHD.
Nevertheless, in the full sibling cohort of over 1.8 million, this association again vanished. That held true overall, as well as separately for childhood infections in months 1-6 and months 7-12. The association vanished altogether both for bacterial infections as well as for viral infections.
The authors concluded, “the results of this nationwide birth cohort study with population and sibling analyses suggest that the association between maternal infection during pregnancy and offspring neurodevelopmental risk is largely due to familial confounding factors.”
Most previous studies of suicide and self-harm risk among persons with ADHD have focused on adolescents and adults. They’ve also tended to be cross-sectional, analyzing data from a population at a specific point in time.
An Australian study team took a different approach, conducting a before-and-after study through the birth cohort of the Longitudinal Study of Australian Children (LSAC), comprising 5,107 children who have been followed up every two years since birth.
The diagnosis of ADHD was based on parents reporting that their child had received a diagnosis of ADHD at or before age ten.
Suicide and self-harm were defined as children’s self-report at age 14 of any thought or attempt of suicide and self-harm respectively over the past year.
The team adjusted for the following confounders: socioeconomic status, birth weight, ADHD medication history, maternal education level, maternal age at birth, experience in bullying victimization at age 12, and depression score based on Short Mood and Feelings Questionnaire (SMFQ).
Of the 5,107 participants, 3,696 had all the valid data required for analysis and were included in the final cohort. Of these, 3.6% were diagnosed with ADHD by age 10.
With diagnosis of ADHD at age 10 and all other factors held constant:
Both depression and exposure to bullying were statistically significant mediators for the relationship. Nevertheless, depression and exposure to bullying each accounted for well under 10% of the overall effect.
Neither socioeconomic status nor maternal factors had any significant mediating effect on outcomes.
Conclusion:
The authors concluded, “This study provides compelling evidence that children diagnosed with ADHD at the age of 10 years face significantly elevated risks of experiencing suicidal thoughts, planning, or attempts, as well as self-harm, by the age of 14 years, which underscores the critical importance of recognizing and addressing these heightened risks in children with ADHD.”
While factors like depression and bullying contribute, ADHD itself remains a key risk factor. Early intervention and strong mental health support are crucial to protecting these children’s well-being.
Noting that “Recent research has demonstrated that some gut bacteria can affect the nervous system,” and speculating that “dysregulation in the gut microbiota may increase the incidence of ADHD by overproducing reactive oxygen and nitrogen species, thereby causing neuroinflammation and oxidative stress”, a Taiwanese study team decided to explore whether early-life use of antibiotics – in the first two years – is associated with increased risk of subsequent diagnosis of ADHD.
Because Taiwan has a single-payer national health insurance system that covers 99.8% of the island’s population, they were able to use the system’s National Health Insurance Research Database (NHIRD) and Maternal and Child Health Database (TMCHD) to include all 1.6 million children born between 2004 and 2012.
Of these, a little over 1.1 million were given antibiotics before turning two years old, and just over 460,000 were not given antibiotics in the same time frame.
The mean follow-up period for records of subsequent ADHD diagnoses was seven years.
The team adjusted for confounding variables: sex, gestational age at birth (weeks), and birth weight (grams) of the children, and age at birth (years), insurance amount (New Taiwan Dollar (TWD)), insurance location, method of delivery, comorbidities, and medication used during pregnancy.
With these adjustments, early-life antibiotics use was associated with a 12% increase in likelihood of being subsequently diagnosed with ADHD.
However, looking at the effects of antibiotics as an undifferentiated grouping turned out to be misleading, because the association was limited to only some classes of antibiotics.
Penicillins were associated with a 22% increase in risk of subsequent ADHD diagnosis, cephalosporins with a 10% increase.
On the other hand, there was absolutely no such association for tetracyclines, macrolides, and quinolones.
The Take-Away:
This study found that children in Taiwan who took certain types of antibiotics before age 2 had a slightly higher risk of developing ADHD later in life. More work is needed to determine if this finding is due to unmeasured confounding before a causal link can be concluded.
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