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October 23, 2023
Guanfacine extended-release(GXR) is a non-stimulant α2A-adrenergic receptor agonist, approved worldwide for ADHD in children and adolescents.
A Japanese research team set out to explore the long-term administration of once-daily GXR in adults with ADHD over a year of treatment. Their primary objective was to evaluate the safety, and the secondary objective was to evaluate efficacy.
This was an open-label trial. Open-label trials are the opposite of double-blind trials. In a double-blind trial, neither the researchers nor the participants know what treatment they participants are receiving. In an open-label trial, on the other hand, both the researchers and participants know what treatment the participant is receiving, which can introduce significant bias. These studies are therefore at the lowest rung in the evidentiary base.
It is worth noting, however, that the risk of bias would be primarily for efficacy, and the primary aim of the trial was to evaluate safety.
The trial was funded by the manufacturer, but preregistered, a way of assuring that results would be released regardless of the outcome.
The study population consisted of 191 ADHD patients 18 and older at 71 locations in Japan. There was no control population. The 50-week flexible titrated dosing treatment period was followed by a 2-week period over which doses were gradually reduced, and then a one-week follow-up period. That means the trial covered an entire year. Of the enrolled patients, 67 dropped out, mostly due to adverse events, leaving 124 patients after the trial.
A total of 830 treatment-emergent adverse events (TEAEs) were reported by 180 patients. One in five patients (34)discontinued treatment due to adverse events. The most commonly reported adverse events were somnolence, thirst, nasopharyngitis, decreased blood pressure, postural dizziness, bradycardia (abnormally slow heartbeat), malaise, constipation, and dizziness. Except for nasopharyngitis, all were considered related to the medication. There were two serious adverse events, one unrelated to the medication, the other a supraventricular tachycardia (abnormally fast heart rhythm arising from improper electrical activity in the upper part of the heart) in a patient simultaneously medicated for a preexisting condition. The patient recovered after treatment and discontinuation of GXR.
The main TEAEs resulting in Discontinuation were somnolence (nine patients), blood pressure reduction (eight patients), malaise (six patients), and bradycardia (four patients, with only one case considered severe), and postural dizziness (three patients) or dizziness(three patients).
Significant reductions in ADHD scores and improvements in executive functioning were measured across the study population following a year's GXR treatment. Again, this was not the primary aim of the trial, and double-blinded randomized controlled trials are the gold standard.
The authors concluded that "there were no new or unexpected safety concerns" and "patients who received dose-optimized GXR had improvements in multiple aspects of ADHD, including symptoms, QoL [Quality of Life], and executive functioning," but acknowledged, "There was a potential for observer bias because of the open-label nature of the study, and the findings may not be representative of real-world settings because patients with psychiatric or cardiovascular comorbidities, which are common in patients with ADHD, were excluded. In addition, there was a potential bias favoring safety and efficacy for continuing patients because those who discontinued owing to adverse events or lack of efficacy were not eligible for inclusion."
Akira Iwanami, Kazuhiko Saito, Masakazu Fujiwara, Daiki Okutsu, and Hironobu Ichikawa, "Safety and efficacy of guanfacine extended-release in adults with attention-deficit/hyperactivity disorder: an open-label, long-term, phase 3 extension study," BMC Psychiatry(2020), https://doi.org/10.1186/s12888-020-02867-8.
While ADHD is a developmental disorder, shaped by biology and genetics, growing evidence shows that it is also influenced by the social and environmental conditions in which children grow up. Research on the social determinants of health emphasizes that development is shaped not only by biology but also by factors such as family income, access to healthcare, neighborhood safety, and material stability. These factors can affect both how developmental challenges appear and whether they are recognized and diagnosed.
Children facing socioeconomic disadvantage consistently show higher risks of developmental and behavioral difficulties. Chronic stress linked to poverty – including financial strain, food insecurity, and limited access to resources – has been associated with problems in attention, emotional regulation, and daily functioning. Children from lower-income families also tend to experience more severe ADHD symptoms and face greater barriers to ongoing care.
Neighborhood conditions matter as well. Unsafe environments can limit opportunities for play and social interaction while increasing caregiver stress, all of which may influence children’s behavior and development. Material hardships, such as food insecurity, can further undermine stability at home.
The Study:
The study analyzed six years of data from the National Survey of Children’s Health (2018–2023), covering more than 205,000 U.S. children aged 3 to 17. After accounting for age, sex, race and ethnicity, region, family structure, survey year, and other social factors, the researchers found a strong income gradient in ADHD prevalence. Compared with children in households earning at least four times the federal poverty level, those in households earning two to four times that level had 28 percent higher odds of ADHD. Odds rose to 70 percent higher in households earning one to two times the poverty level, and more than doubled among children living below the poverty line.
Parental education showed a similar pattern. Compared with children whose parents had completed college, ADHD odds were 20 percent higher among those whose parents had some college education, 40 percent higher among those whose parents had only a high school education, and 80 percent higher among those whose parents had not finished high school.
Children living in unsafe neighborhoods had nearly twice the odds of ADHD compared with those in safe neighborhoods, and food insecurity was also linked to almost double the odds.
By contrast, race and ethnicity alone were associated with much smaller differences. Compared with non-Hispanic White children, children in non-Hispanic Black households had an 18 percent higher likelihood of ADHD, while children in Hispanic households had a 25 percent lower likelihood. No substantial differences were observed for children from other or multiracial households.
Conclusion and Takeaway:
The study team concluded, “Children living in lower-income households, experiencing food insecurity, and residing in unsafe neighborhoods consistently showed higher prevalence and higher adjusted odds of both conditions. … Overall, these findings reinforce the need to view neurodevelopmental disorders within a broader social and structural framework.”
It should be noted that this study is not aiming to name social factors as direct causes of ADHD. Rather, it points to socioeconomic disparities as contributing to the way ADHD develops and how it is treated. This type of research, as well as acknowledging barriers to care, is crucial for clinicians, counselors, teachers, etc., to consider when working with youth with ADHD.
Counting umbilical cord vessels is standard in prenatal ultrasounds and confirmed at birth. Single umbilical artery (SUA) occurs in about 1 in 200 cases, with roughly 10% associated with anomalies, including central nervous system defects. Isolated SUA (iSUA) means one artery is missing without other structural issues.
Research on SUA, especially isolated iSUA, and childhood neurodevelopmental disorders (NDD) is limited and inconclusive. iSUA is linked to preterm birth and small-for-gestational age (SGA), both of which are NDD risk factors.
This Norwegian nationwide population study aimed to assess NDD risk in children with iSUA at birth, the influence of sex, and how preterm birth and SGA mediate this relationship.
The nation’s universal single-payer health insurance and comprehensive population registries made it possible to analyze all 858,397 single births occurring from 1999 to 2013, with follow-up continuing through 2019. Among these cases, 3,532 involved iSUA.
After adjusting for confounders such as parental age, education, and maternal health factors, no overall link was found between iSUA and later ADHD diagnosis. However, females with iSUA had about a 40% higher risk of subsequent ADHD compared to those without iSUA, even after adjustment.
The authors concluded, “The present study indicates that iSUA is weakly associated with ID [intellectual disability] and ADHD, and these associations are influenced by sex. This association is mediated negligibly through preterm birth and SGA. The associations were not clinically significant, and the absence of associations of iSUA with other NDD is reassuring. This finding can be useful in the counseling of expectant parents of fetuses diagnosed with iSUA.”
Refractive errors, such as myopia (nearsightedness), hyperopia (farsightedness), and astigmatism (distorted vision due to irregular curvature of the eye or lens), are common worldwide. These conditions affect 12%, 5%, and 15% of children, and rise significantly in adults to 26.5%, 31%, and 40%. Additionally, strabismus (misalignment of the eyes) and amblyopia (reduced vision in one eye from uneven image formation, often linked to strabismus) occur globally at rates of 2% and 1.4%, respectively.
Visual impairment can affect children’s concentration in school, and studies suggest a link between eye disorders and ADHD.
To investigate this relationship, two researchers – one based in the US and the other in Israel –carried out a nationwide retrospective cohort study using electronic medical records of all insured individuals aged 5 to 30 who were part of Maccabi Health Services, Israel’s second largest health maintenance organization, between 2010 and 2022.
Of over 1.6 million insured members (2010–2020), inclusion/exclusion criteria and propensity score matching for age and sex were applied, along with a one-year wash-out period between the first eye diagnosis and ADHD diagnosis. In total, 221,707 cases were matched with controls without eye disorders at a 1:2 ratio, resulting in a cohort of 665,121 participants.
Overall, those with any previous eye diagnosis were 40% more likely to have a subsequent ADHD diagnosis. This was slightly higher for females (45%) than for males (35%). It was also slightly higher for children and adolescents (42%) than for adults (37%).
More specifically:
The authors concluded that eye disorders are associated with ADHD. They noted these associations were more marked in females and children and adolescents, although, as noted above, those differences were small. They recommended that primary care providers and neurologists consider risk stratification for early screening, and that ophthalmologists refer high-risk patients for ADHD evaluation.
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