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.
Given the persistence of ADHD and its adverse effects on children and adolescents, one might expect caregivers to face greater parenting challenges, with potential effects on their own mental health.
To what extent do parenting stress, depression, and – at the extreme – even suicidal ideation manifest themselves among caregivers of ADHD patients as opposed to caregivers of children and adolescents without ADHD?
A pair of Korean researchers made use of their country’s single-payer health insurance system, which maintains records on virtually the entire population, to perform a nationwide population study. They used data from the Korean National Health and Nutrition Examination Surveys (KNHANES) covering the decade from 2011 to 2020. KNHANES is an annual survey using a sophisticated sampling design conducted by the Korean Ministry of Health and Welfare to represent the entire population of South Korea.
The analysis included 14,428 individuals who had children younger than 19 at the time of participation. All were asked whether their child had ever been diagnosed with ADHD by a physician. The mental health problems of the parents were assessed in terms of perceived stress, depressive symptoms, and suicidality.
Of the 14,428 participants, 8,298 (57.5 %) were mothers and 6,130 (42.5 %) were fathers. Of the mothers, 116 (1.4 %) had a child with ADHD, and of the fathers, 86 (1.4 %) had a child with ADHD.
The researchers adjusted for the following confounders: age of caregiver, education level, household income, area of residence, employment status, alcohol consumption, smoking status, cohabitation status, number of children, and child’s age.
After adjustment, mothers of ADHD patients fared significantly worse than mothers of typically developing children on all three categories of mental health problems. They were 67% more likely to report higher stress, three times as likely to report symptoms of depression, and 2.5 times more likely to report suicidal ideation.
Yet that pattern did not carry over to fathers, where there was no significant difference in mental health indicators between fathers of children with ADHD and fathers of children without ADHD.
The authors concluded, “Parents of children with ADHD, especially mothers, need community support and public health attention to help alleviate their mental health problems.”
Background:
ADHD is commonly accompanied by psychiatric comorbidities that complicate its diagnosis and treatment. Roughly two out of three affected children and adolescents have one or more comorbid psychiatric disorder.
Because the peak age of ADHD onset is typically a decade or more earlier than those for schizophrenia, depressive disorder, or bipolar disorder, it is essential to explore these comorbidities over an extended period. Populations studies help researchers identify broader patterns and trends within an entire population and includes adults as well as children. This type of study provides unique insights into the population at large, rather than a sample group.
In earlier studies the maximum follow-up period was twelve years, insufficient in view of the roughly ten years between onset of ADHD and onset of major psychiatric disorders. Also, previous nationwide population studies have included less than 150,000 participants.
This study, relying on data from South Korea’s universal single-payer health insurance system, included over one and a half million individuals. Persons previously diagnosed with depression, bipolar disorder, tic disorder, or schizophrenia were excluded.
382,434 individuals had been diagnosed with ADHD, while 1,169,279 were without an ADHD diagnosis.
Propensity score matching ensured that potential confounders, both sociodemographic and clinical, were equalized for the ADHD and control groups. After matching, there were 353,898 individuals in each group.
After these adjustments, individuals in the ADHD group were at least an order of magnitude more likely to subsequently be diagnosed with psychiatric disorders than their peers without an ADHD diagnosis:
Conclusion:
The Korean study team concluded, “Overall, our findings suggest that upon prolonged examination, the risk of subsequent diagnoses of other psychiatric disorders in individuals with ADHD appears to be higher than that reported previously. … Therefore, patients with ADHD should be carefully screened for the presence of other psychiatric symptoms on a regular basis from an earlier age … It is advisable to have a follow-up period extending beyond 10 years to sufficiently identify the occurrence of comorbid disorders in patients with ADHD.”
Children with ADHD often face challenges in social interactions, leading to long-term consequences if not properly addressed. While various interventions exist, many fail to consider the broader social context in which these children interact. A recent study conducted in Bergen, Norway, explored how primary school teachers perceive their role in supporting children with ADHD who struggle socially and the strategies they use to assist them.
Researchers conducted semi-structured interviews with five focus groups of primary school teachers. Using reflexive thematic analysis, they identified two major themes:
Rather than relying on standardized interventions, teachers tailored their strategies to foster an inclusive and supportive social environment. Their methods included both active participation in social situations and behind-the-scenes efforts to encourage peer inclusion and understanding.
This study underscores the need to move beyond labels and recognize children with ADHD as individuals with distinct social needs. Teachers play a crucial role in shaping these children’s experiences, using flexible and personalized approaches to promote positive social interactions. By integrating social context and individualized support, educators can help children with ADHD build meaningful connections and navigate their social world more effectively.
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