March 18, 2024
An international study team has just reported findings from a series of meta-analyses exploring associations between ADHD medications and headaches in children and adolescents.
First, to compare headache occurrence in individuals with ADHD to those without ADHD, the team performed a very large meta-analysis of twelve studies with over 2.7 million children and adolescents. Those with ADHD had twice the rate of headaches.
There was no indication of publication bias, but there was considerable variation (heterogeneity) among studies, with crude odds ratios spanning from 0.9 to 3.37. Nevertheless, ten of the twelve studies pointed to higher odds among children and adolescents with ADHD. The four studies that controlled for age, sex, race, and other socioeconomic status variables reaffirmed the finding of a doubling of headache risk, this time with acceptable heterogeneity.
Three studies with a combined 7,755 participants found no difference in tension headaches, but five studies with over a quarter million persons found more than a doubling of the rate of migraine in children and adolescents with ADHD.
Next, the team performed meta-analyses of 58 randomized controlled trials (RCTs) of specific ADHD medications that met eligibility criteria for their systematic review. Because only a single eligible RCT apiece looked at bupropion and clonidine, these ADHD medications could not be included in the meta-analyses.
A meta-analysis of ten RCTs with a total of 2,672 participants found absolutely no association between use of amphetamines (including lisdexamphetamine) and headaches. Variation (heterogeneity) between studies was minimal, and there was no sign of publication bias.
A smaller meta-analysis of six RCTs with a combined 818 participants found a 24% increase in headaches among modafinil users, but it was not statistically significant, perhaps because of the much smaller combined sample size.
A meta-analysis of 17 RCTs with a total of 3,371 participants found a 33% increase in headache occurrence among methylphenidate users over placebo. Between-study variation (heterogeneity) was negligible, and there was absolutely no sign of publication bias.
Similarly, a meta-analysis of 22 RCTs with a combined 3,857 participants reported a 29% increase in headache occurrence among atomoxetine users over placebo. Again, heterogeneity between studies was negligible, with absolutely no indication of publication bias.
Finally, a meta-analysis of eight RCTs with 1,956 participants found a 43% increase in headache occurrence among guanfacine users over placebo. Once again, with negligible heterogeneity and no indication of publication bias.
Pei-Yin Pan, Ulf Jonsson, Sabriye Selin Şahpazoğlu Çakmak, Alexander Häge, Sarah Hohmann, Hjalmar Nobel Norrman, Jan K. Buitelaar, Tobias Banaschewski, Samuele Cortese, David Coghill, and Sven Bölte, “Headache in ADHD as comorbidity and a side effect of medications: a systematic review and meta-analysis,” Psychological Medicine (2022) 52, 14-25, https://doi.org/10.1017/S0033291721004141.
Background:
Noting that “the results of previous investigations into the therapeutic benefits of probiotics in the treatment of ADHD symptoms remain inconsistent,” a Taiwanese study team conducted a systematic search of the peer-reviewed medical literature to perform a meta-analysis.
The Study:
The team identified seven randomized controlled trials (RCTs) that met criteria for inclusion: focusing on children and adolescents under 18, with ADHD diagnoses, comparing probiotic interventions with placebo, and using standardized behavioral rating scales to assess ADHD symptoms.
Meta-analysis of these seven RCTs with a combined total of 342 participants found no significant improvement in ADHD symptoms. In fact, six of the seven RCTs clustered tightly around zero effect, while the seventh – a small sample (38) outlier – reported a very large effect size improvement.
Meta-analysis of the three RCTs with a combined 154 individuals that used probiotics with single strains of microorganisms showed absolutely no improvement in ADHD symptoms with no between-study variation (heterogeneity).
Meta-analysis of the four RCTs with a total of 188 participants that used multiple strains pointed to a medium – but statistically nonsignificant – effect size improvement, with high heterogeneity. Removing the previously mentioned outlier RCT collapsed the effect size to zero.
Two of the RCTs (with 72 total individuals), including the outlier, offered probiotics in conjunction with methylphenidate treatment. Meta-analysis of the other five RCTs with 270 persons that were structured around pure supplementation yielded absolutely no improvement in ADHD symptoms with no heterogeneity.
Meta-analyses of the four RCTs with a combined total of 238 participants that examined ADHD subtypes reported no effect on either inattention symptoms or hyperactivity/impulsivity symptoms.
Trivially, given the lack of efficacy, probiotic regimens were tolerated as well as placebo.
The Take-Away:
Ultimately, this meta-analysis found no evidence that probiotics improve ADHD symptoms in children and adolescents. Across seven randomized controlled trials, results consistently showed no significant benefit compared to a placebo. While probiotics were well-tolerated, they did not meaningfully impact inattention, hyperactivity, or impulsivity. These findings suggest that probiotics, whether single or multi-strain, are not an effective treatment for ADHD.
Background:
Noting that “Previous research has demonstrated that attention significantly influences various domains such as language, literacy, and mathematics, making it a crucial determinant of academic achievement,” an international study team performed a comprehensive search of the peer-reviewed medical literature for studies evaluating effects of physical activity on attention.
The Study:
The team’s meta-analysis of ten studies with a combined total of 474 participants found moderate reductions in attention problems following physical activity. They found no significant evidence of publication bias, but there was considerable variation in outcomes between studies (heterogeneity).
To tease out the reasons for this variability, the team looked at specific attributes of the physical activity regimens used in the studies.
The seven studies with 168 participants that involved mentally engaging physical activity reported large reductions in attention problems, whereas the three studies with 306 persons that used aerobic exercise found no reduction whatsoever. Heterogeneity in the former was reduced, in the latter all but disappearing.
Comparing studies with other interventions as control groups (6 studies, 393 participants) with those with no intervention as control (4 studies, 81 participants), the former reported only small improvements in attention problems, while the latter reported large improvements.
Duration of physical activity made little difference. The four studies with physical activity of an hour or more reported better outcomes than the six with less than an hour, but the difference was not significant.
Greater frequency did make a difference, but in a counterintuitive way. The seven studies with one or two physical activity interventions per week (162 participants) reported large reductions in attention problems, whereas the three studies with three or more interventions per week (312 participants) showed no improvement.
Conclusion:
The authors concluded, “Our study suggests that cognitively engaging exercise is more effective in improving attention problems in school-aged children with ADHD.” Moreover, “the benefits of improved attention in school-age children with ADHD are not necessarily positively correlated with higher frequency and longer duration of physical activity.” Also keep in mind that exercise, while important for all children, should not replace medical and psychological treatments for the disorder.
The National Health Interview Survey (NHIS) is conducted annually by the National Center for Health Statistics at the Centers for Disease Control and Prevention. The NHIS is done primarily through face-to-face computer-assisted interviews in the homes of respondents. But telephone interviews are substituted on request, or where travel distances make in-home visits impractical.
For each interviewed family, only one sample child is randomly selected by a computer program.
The total number of households with a child or adolescent aged 3-17 for the years 2018 through 2021 was 26,422.
Based on responses from family members, 9.5% of the children and adolescents randomly surveyed throughout the United States had ADHD.
This proportion varied significantly based on age, rising from 1.5% for ages 3-5 to 9.6% for ages 6-11 and to 13.4% for ages 12-17.
There was an almost two-to-one gap between the 12.4% prevalence among males and the 6.6% prevalence among females.
There was significant variation by race/ethnicity. While rates among non-Hispanic whites (11.1%) and non-Hispanic blacks (10.5%) did not differ significantly, these two groups differed significantly from Hispanics (7.2%) and Others (6.6%).
There were no significant variations in ADHD prevalence based on highest education level of family members.
But family income had a significant relationship with ADHD prevalence, especially at lower incomes. For family incomes under the poverty line, the prevalence was 12.7%. That dropped to 10.3% for family incomes above the poverty level but less than twice that level. For all others it dropped further to about 8.5%. Although that might seem like poverty causes ADHD, we cannot draw that conclusion. Other data indicate that adults with ADHD have lower incomes. That would lead to more ADHD in kids from lower income families.
There was also significant geographic variation in reported prevalence rates. It was highest in the South, at 11.3%, then the Midwest at 10%, the Northeast at 9.1%, with a jump down to 6.9% in the West.
Overall ADHD prevalence did not vary significantly by year over the four years covered by this study.
This study highlights a consistently high prevalence of developmental disabilities among U.S. children and adolescents, with notable increases in other developmental delays and co-occurring learning and intellectual disabilities from 2018 to 2021. While the overall prevalence remained stable, these findings emphasize the need for continued research into potential risk factors and targeted interventions to address developmental challenges in youth.
It is also important to note that this study assessed the prevalence of ADHD being diagnosed by healthcare professionals. Due to variations in healthcare accessibility across the country, the true prevalence of ADHD may differ still.
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